731 results on '"Joel H Kramer"'
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2. Neurophysiological trajectories in Alzheimer’s disease progression
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Kiwamu Kudo, Kamalini G Ranasinghe, Hirofumi Morise, Faatimah Syed, Kensuke Sekihara, Katherine P Rankin, Bruce L Miller, Joel H Kramer, Gil D Rabinovici, Keith Vossel, Heidi E Kirsch, and Srikantan S Nagarajan
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Alzheimer's disease ,magnetoencephalography ,biomarkers ,electrophysiology ,functional connectivity ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β and misfolded tau proteins causing synaptic dysfunction, and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. The increases in neural synchrony in the delta-theta band and the decreases in the alpha and beta bands showed progressive changes throughout the stages of the EBM. Decreases in alpha and beta band synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. The long-range synchrony effects were greater than the local synchrony, indicating a greater sensitivity of connectivity metrics involving multiple regions of the brain. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.
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- 2024
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3. Pittsburgh Sleep Quality Index (PSQI) responses are modulated by total sleep time and wake after sleep onset in healthy older adults.
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Jennifer Zitser, Isabel Elaine Allen, Neus Falgàs, Michael M Le, Thomas C Neylan, Joel H Kramer, and Christine M Walsh
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Medicine ,Science - Abstract
ObjectivesTo investigate the objective sleep influencers behind older adult responses to subjective sleep measures, in this case, the Pittsburgh Sleep Quality Index (PSQI). Based on previous literature, we hypothesized that SE would be associated with PSQI reported sleep disruption. Furthermore, because SOL increases progressively with age and it tends to be easily remembered by the patients, we also expected it to be one of the main predictors of the perceived sleep quality in the elderly.MethodsWe studied 32 cognitively healthy community-dwelling older adults (age 74 ± 0.3 years) who completed an at-home sleep assessment (Zeo, Inc.) and the PSQI. Linear mixed models were used to analyze the association of the objective sleep parameters (measured by the Zeo) with the PSQI total score and sub-scores, adjusting for age, gender, years of education and likelihood of sleep apnea.ResultsObjective sleep parameters did not show any association with the PSQI total score. We found that objective measures of Wake after sleep onset (WASO, % and min) were positively associated with the PSQI sleep disturbance component, while SE and Total Sleep Time (TST) were negatively associated with PSQI sleep disturbance. Lastly, objective SE was positively associated with PSQI SE.ConclusionsOur findings showed that WASO, SE and TST, are associated with PSQI sleep disturbance, where the greater WASO, overall lower SE and less TST, were associated with increased subjective report of sleep disturbance. As expected, subjective (PSQI) and objective measures of SE were related. However, PSQI total score did not relate to any of the objective measures. These results suggest that by focusing on the PSQI total score we may miss the insight this easily administered self-report tool can provide. If interpreted in the right way, the PSQI can provide further insight into cognitively healthy older adults that have the likelihood of objective sleep disturbance.
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- 2022
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4. Reduced utilitarian willingness to violate personal rights during the COVID-19 pandemic.
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Rea Antoniou, Heather Romero-Kornblum, J Clayton Young, Michelle You, Joel H Kramer, and Winston Chiong
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Medicine ,Science - Abstract
The COVID-19 pandemic poses many real-world moral dilemmas, which can pit the needs and rights of the many against the needs and rights of the few. We investigated moral judgments in the context of the contemporary global crisis among older adults, who are at greatest personal risk from the pandemic. We hypothesized that during this pandemic, individuals would give fewer utilitarian responses to hypothetical dilemmas, accompanied by higher levels of confidence and emotion elicitation. Our pre-registered analysis (https://osf.io/g2wtp) involved two waves of data collection, before (2014) and during (2020) the COVID-19 pandemic, regarding three categories of moral dilemmas (personal rights, agent-centered permissions, and special obligations). While utilitarian responses considered across all categories of dilemma did not differ, participants during the 2020 wave gave fewer utilitarian responses to dilemmas involving personal rights; that is, they were less willing to violate the personal rights of others to produce the best overall outcomes.
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- 2021
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5. Specific cortical and subcortical grey matter regions are associated with insomnia severity.
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Neus Falgàs, Ignacio Illán-Gala, Isabel E Allen, Paige Mumford, Youssef M Essanaa, Michael M Le, Michelle You, Lea T Grinberg, Howard J Rosen, Thomas C Neylan, Joel H Kramer, and Christine M Walsh
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Medicine ,Science - Abstract
BackgroundThere is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether there is a gradient association between these regions and the severity of insomnia in older adults who could be at risk for dementia. Since depressive symptoms and sleep apnea can both feature insomnia-related factors, can impact brain health and are frequently present in older populations, it is important to include them when studying insomnia. Therefore, our goal was to investigate GM changes associated with insomnia severity in a cohort of healthy older adults, taking into account the potential effect of depression and sleep apnea as well. We hypothesized that insomnia severity is correlated with 1) cortical regions responsible for regulation of sleep and emotion, such as the orbitofrontal cortex and, 2) subcortical regions, such as the putamen.Methods120 healthy subjects (age 74.8±5.7 years old, 55.7% female) were recruited from the Hillblom Healthy Aging Network at the Memory and Aging Center, UCSF. All participants were determined to be cognitively healthy following a neurological evaluation, neuropsychological assessment and informant interview. Participants had a 3T brain MRI and completed the Insomnia Severity Index (ISI), Geriatric Depression Scale (GDS) and Berlin Sleep Questionnaire (BA) to assess sleep apnea. Cortical thickness (CTh) and subcortical volumes were obtained by the CAT12 toolbox within SPM12. We studied the correlation of CTh and subcortical volumes with ISI using multiple regressions adjusted by age, sex, handedness and MRI scan type. Additional models adjusting by GDS and BA were also performed.ResultsISI and GDS were predominantly mild (4.9±4.2 and 2.5±2.9, respectively) and BA was mostly low risk (80%). Higher ISI correlated with lower CTh of the right orbitofrontal, right superior and caudal middle frontal areas, right temporo-parietal junction and left anterior cingulate cortex (pConclusionsOur findings highlight a relationship between insomnia severity and brain health, even with relatively mild insomnia, and independent of depression and likelihood of sleep apnea. The results extend the previous literature showing the association of specific GM areas (i.e, orbitofrontal, insular and temporo-parietal junction) not just with the presence of insomnia, but across the spectrum of severity itself. Moreover, our results suggest subcortical structures (i.e., putamen) are involved as well. Longitudinal studies are needed to clarify how these insomnia-related brain changes in healthy subjects align with an increased risk of dementia.
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- 2021
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6. REM sleep is associated with white matter integrity in cognitively healthy, older adults.
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Marie Altendahl, Devyn L Cotter, Adam M Staffaroni, Amy Wolf, Paige Mumford, Yann Cobigo, Kaitlin Casaletto, Fanny Elahi, Leslie Ruoff, Samirah Javed, Brianne M Bettcher, Emily Fox, Michelle You, Rowan Saloner, Thomas C Neylan, Joel H Kramer, and Christine M Walsh
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Medicine ,Science - Abstract
There is increasing awareness that self-reported sleep abnormalities are negatively associated with brain structure and function in older adults. Less is known, however, about how objectively measured sleep associates with brain structure. We objectively measured at-home sleep to investigate how sleep architecture and sleep quality related to white matter microstructure in older adults. 43 cognitively normal, older adults underwent diffusion tensor imaging (DTI) and a sleep assessment within a six-month period. Participants completed the PSQI, a subjective measure of sleep quality, and used an at-home sleep recorder (Zeo, Inc.) to measure total sleep time (TST), sleep efficiency (SE), and percent time in light sleep (LS), deep sleep (DS), and REM sleep (RS). Multiple regressions predicted fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum as a function of total PSQI score, TST, SE, and percent of time spent in each sleep stage, controlling for age and sex. Greater percent time spent in RS was significantly associated with higher FA (β = 0.41, p = 0.007) and lower MD (β = -0.30, p = 0.03). Total PSQI score, TST, SE, and time spent in LS or DS were not significantly associated with FA or MD (p>0.13). Percent time spent in REM sleep, but not quantity of light and deep sleep or subjective/objective measures of sleep quality, positively predicted white matter microstructure integrity. Our results highlight an important link between REM sleep and brain health that has the potential to improve sleep interventions in the elderly.
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- 2020
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7. An IL-18-centered inflammatory network as a biomarker for cerebral white matter injury.
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Marie Altendahl, Pauline Maillard, Danielle Harvey, Devyn Cotter, Samantha Walters, Amy Wolf, Baljeet Singh, Visesha Kakarla, Ida Azizkhanian, Sunil A Sheth, Guanxi Xiao, Emily Fox, Michelle You, Mei Leng, David Elashoff, Joel H Kramer, Charlie Decarli, Fanny Elahi, and Jason D Hinman
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Medicine ,Science - Abstract
Chronic systemic sterile inflammation is implicated in the pathogenesis of cerebrovascular disease and white matter injury. Non-invasive blood markers for risk stratification and dissection of inflammatory molecular substrates in vivo are lacking. We sought to identify whether an interconnected network of inflammatory biomarkers centered on IL-18 and all previously associated with white matter lesions could detect overt and antecedent white matter changes in two populations at risk for cerebral small vessel disease. In a cohort of 167 older adults (mean age: 76, SD 7.1, 83 females) that completed a cognitive battery, physical examination, and blood draw in parallel with MR imaging including DTI, we measured cerebral white matter hyperintensities (WMH) and free water (FW). Concurrently, serum levels of a biologic network of inflammation molecules including MPO, GDF-15, RAGE, ST2, IL-18, and MCP-1 were measured. The ability of a log-transformed population mean-adjusted inflammatory composite score (ICS) to associate with MR variables was demonstrated in an age and total intracranial volume adjusted model. In this cohort, ICS was significantly associated with WMH (β = 0.222, p = 0.013), FW (β = 0.3, p = 0.01), and with the number of vascular risk factor diagnoses (r = 0.36, p
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- 2020
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8. Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy
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Orit H Lesman-Segev, Renaud La Joie, Melanie L Stephens, Ida Sonni, Richard Tsai, Viktoriya Bourakova, Adrienne V Visani, Lauren Edwards, James P O'Neil, Suzanne L Baker, Raquel C Gardner, MD, Mustafa Janabi, Kiran Chaudhary, David C Perry, Joel H Kramer, Bruce L Miller, William J Jagust, and Gil D Rabinovici
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Objective: To characterize individual and group-level neuroimaging findings in patients at risk for Chronic Traumatic Encephalopathy (CTE). Methods: Eleven male patients meeting criteria for Traumatic Encephalopathy Syndrome (TES, median age: 64) underwent neurologic evaluation, 3-Tesla MRI, and PET with [18F]-Flortaucipir (FTP, tau-PET) and [11C]-Pittsburgh compound B (PIB, amyloid-PET). Six patients underwent [18F]-Fluorodeoxyglucose-PET (FDG, glucose metabolism). We assessed imaging findings at the individual patient level, and in group-level comparisons with modality-specific groups of cognitively normal older adults (CN). Tau-PET findings in patients with TES were also compared to a matched group of patients with mild cognitive impairment or dementia due to Alzheimer's disease (AD). Results: All patients with TES sustained repetitive head injury participating in impact sports, ten in American football. Three patients met criteria for dementia and eight had mild cognitive impairment. Two patients were amyloid-PET positive and harbored the most severe MRI atrophy, FDG hypometabolism, and FTP-tau PET binding. Among the nine amyloid-negative patients, tau-PET showed either mildly elevated frontotemporal binding, a “dot-like” pattern, or no elevated binding. Medial temporal FTP was mildly elevated in a subset of amyloid-negative patients, but values were considerably lower than in AD. Voxelwise analyses revealed a convergence of imaging abnormalities (higher FTP binding, lower FDG, lower gray matter volumes) in frontotemporal areas in TES compared to controls. Conclusions: Mildly elevated tau-PET binding was observed in a subset of amyloid-negative patients at risk for CTE, in a distribution consistent with CTE pathology stages III-IV. FTP-PET may be useful as a biomarker of tau pathology in CTE but is unlikely to be sensitive to early disease stages. Keywords: Chronic traumatic encephalopathy (CTE), Imaging, Positron emission tomography (PET), Tau, Amyloid, Magnetic resonance imaging (MRI)
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- 2019
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9. Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study.
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Natasha Z R Steele, Jessie S Carr, Luke W Bonham, Ethan G Geier, Vincent Damotte, Zachary A Miller, Rahul S Desikan, Kevin L Boehme, Shubhabrata Mukherjee, Paul K Crane, John S K Kauwe, Joel H Kramer, Bruce L Miller, Giovanni Coppola, Jill A Hollenbach, Yadong Huang, and Jennifer S Yokoyama
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Medicine - Abstract
BackgroundAlzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations.Methods and findingsBuilding on prior work linking the HLA to AD, we used a robust imputation method on two separate case-control cohorts to examine the relationship between HLA haplotypes and AD risk in 309 individuals (191 AD, 118 cognitively normal [CN] controls) from the San Francisco-based University of California, San Francisco (UCSF) Memory and Aging Center (collected between 1999-2015) and 11,381 individuals (5,728 AD, 5,653 CN controls) from the Alzheimer's Disease Genetics Consortium (ADGC), a National Institute on Aging (NIA)-funded national data repository (reflecting samples collected between 1984-2012). We also examined cerebrospinal fluid (CSF) biomarker measures for patients seen between 2005-2007 and longitudinal cognitive data from the Alzheimer's Disease Neuroimaging Initiative (n = 346, mean follow-up 3.15 ± 2.04 y in AD individuals) to assess the clinical relevance of identified risk haplotypes. The strongest association with AD risk occurred with major histocompatibility complex (MHC) haplotype A*03:01~B*07:02~DRB1*15:01~DQA1*01:02~DQB1*06:02 (p = 9.6 x 10-4, odds ratio [OR] [95% confidence interval] = 1.21 [1.08-1.37]) in the combined UCSF + ADGC cohort. Secondary analysis suggested that this effect may be driven primarily by individuals who are negative for the established AD genetic risk factor, apolipoprotein E (APOE) ɛ4. Separate analyses of class I and II haplotypes further supported the role of class I haplotype A*03:01~B*07:02 (p = 0.03, OR = 1.11 [1.01-1.23]) and class II haplotype DRB1*15:01- DQA1*01:02- DQB1*06:02 (DR15) (p = 0.03, OR = 1.08 [1.01-1.15]) as risk factors for AD. We followed up these findings in the clinical dataset representing the spectrum of cognitively normal controls, individuals with mild cognitive impairment, and individuals with AD to assess their relevance to disease. Carrying A*03:01~B*07:02 was associated with higher CSF amyloid levels (p = 0.03, β ± standard error = 47.19 ± 21.78). We also found a dose-dependent association between the DR15 haplotype and greater rates of cognitive decline (greater impairment on the 11-item Alzheimer's Disease Assessment Scale cognitive subscale [ADAS11] over time [p = 0.03, β ± standard error = 0.7 ± 0.3]; worse forgetting score on the Rey Auditory Verbal Learning Test (RAVLT) over time [p = 0.02, β ± standard error = -0.2 ± 0.06]). In a subset of the same cohort, dose of DR15 was also associated with higher baseline levels of chemokine CC-4, a biomarker of inflammation (p = 0.005, β ± standard error = 0.08 ± 0.03). The main study limitations are that the results represent only individuals of European-ancestry and clinically diagnosed individuals, and that our study used imputed genotypes for a subset of HLA genes.ConclusionsWe provide evidence that variation in the HLA locus-including risk haplotype DR15-contributes to AD risk. DR15 has also been associated with multiple sclerosis, and its component alleles have been implicated in Parkinson disease and narcolepsy. Our findings thus raise the possibility that DR15-associated mechanisms may contribute to pan-neuronal disease vulnerability.
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- 2017
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10. Comparing Volume Loss in Neuroanatomical Regions of Emotion versus Regions of Cognition in Healthy Aging.
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Peter S Pressman, Yuliana Noniyeva, Nick Bott, Shubir Dutt, Virginia Sturm, Bruce L Miller, and Joel H Kramer
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Medicine ,Science - Abstract
Many emotional functions are relatively preserved in aging despite declines in several cognitive domains and physical health. High levels of happiness exist even among centenarians. To address the hypothesis of whether preservation of emotional function in healthy aging may relate to different rates of age-related volume loss across brain structures, we performed two volumetric analyses on structural magnetic resonance neuroimaging of a group of healthy aging research participants using Freesurfer version 5.1. Volumes selected as supporting cognition included bilateral midfrontal and lateral frontal gyri, lateral parietal and temporal cortex, and medial temporal lobes. Volumes supporting emotion included bilateral amygdala, rostral anterior cingulate, insula, orbitofrontal cortex, and nucleus accumbens. A cross-sectional analysis was performed using structural MRI scans from 258 subjects. We found no difference in proportional change between groups. A longitudinal mixed effects model was used to compare regional changes over time in a subset of 84 subjects. Again, there was no difference in proportional change over time. While our results suggest that aging does not collectively target cognitive brain regions more than emotional regions, subgroup analysis suggests relative preservation of the anterior cingulate cortex, with greater volume loss in the nucleus accumbens. Implications of these relative rates of age-related volume loss in healthy aging are discussed and merit further research.
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- 2016
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11. Before it is too late: Professional responsibilities in late-onset Alzheimer’s research and pre-symptomatic prediction
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Silke eSchicktanz, Mark eSchweda, Jesse eBallenger, Patrick eFox, Jodi eHalpern, Joel H Kramer, Guy eMicco, Stephen G Post, Charis eThompson, Robert T Knight, and William J Jagust
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biomarker ,prediction ,Medical Ethics ,Public Engagement ,Cultural Diversity ,recommendations ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The development of a wide array of molecular and neuroscientific biomarkers can provide the possibility to visualize the course of Alzheimer’s disease (AD) at early stages. Many of these biomarkers are aimed at detecting not only a preclinical, but also a pre-symptomatic state. They are supposed to facilitate clinical trials aiming at treatments that attack the disease at its earliest stage or even prevent it. The increasing number of such biomarkers currently tested and now partly proposed for clinical implementation calls for critical reflection on their aims, social benefits and risks. This position paper summarizes major challenges and responsibilities. Its focus is on the ethical and social problems involved in the organization and application, of dementia research as well as in health care provision from a cross-national point of view. The paper is based on a discussion of leading dementia experts from various disciplines, such as neuroscience, neurology, social sciences, and bioethics. We intend to initiate a debate on the need for actions within the researchers’ national and international communities.
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- 2014
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12. Neural Correlates of Cognitive Intervention in Persons at Risk of Developing Alzheimer’s disease
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SM Hadi eHosseini, Joel H Kramer, and Shelli R. Kesler
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Aging ,Neuroimaging ,plasticity ,cognitive training ,mild cognitive impairment (MCI) ,cognitive intervention ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Cognitive training is an emergent approach that has begun to receive increased attention in recent years as a non-pharmacological, cost-effective intervention for Alzheimer’s disease (AD). There has been increasing behavioral evidence regarding training-related improvement in cognitive performance in early stages of AD. Although these studies provide important insight about the efficacy of cognitive training, neuroimaging studies are crucial to pinpoint changes in brain structure and function associated with training and to examine their overlap with pathology in AD. In this study, we reviewed the existing neuroimaging studies on cognitive training in persons at risk of developing AD to provide an overview of the overlap between neural networks rehabilitated by the current training methods and those affected in AD. The data suggest a consistent training-related increase in brain activity in medial temporal, prefrontal, and posterior default mode networks, as well as increase in gray matter structure in frontoparietal and entorhinal regions. This pattern differs from the observed pattern in healthy older adults that shows a combination of increased and decreased activity in response to training. Detailed investigation of the data suggests that training in persons at risk of developing AD mainly improves compensatory mechanisms and partly restores the affected functions. While current neuroimaging studies are quite helpful in identifying the mechanisms underlying cognitive training, the data calls for future multi-modal neuroimaging studies with focus on multi-domain cognitive training, network level connectivity, and individual differences in response to training.
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- 2014
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13. Interleukin-6, age, and corpus callosum integrity.
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Brianne M Bettcher, Christa L Watson, Christine M Walsh, Iryna V Lobach, John Neuhaus, Joshua W Miller, Ralph Green, Nihar Patel, Shubir Dutt, Edgar Busovaca, Howard J Rosen, Kristine Yaffe, Bruce L Miller, and Joel H Kramer
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Medicine ,Science - Abstract
The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories.
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- 2014
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14. Body mass and white matter integrity: the influence of vascular and inflammatory markers.
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Brianne Magouirk Bettcher, Christine M Walsh, Christa Watson, Joshua W Miller, Ralph Green, Nihar Patel, Bruce L Miller, John Neuhaus, Kristine Yaffe, and Joel H Kramer
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Medicine ,Science - Abstract
High adiposity is deleteriously associated with brain health, and may disproportionately affect white matter integrity; however, limited information exists regarding the mechanisms underlying the association between body mass (BMI) and white matter integrity. The present study evaluated whether vascular and inflammatory markers influence the relationship between BMI and white matter in healthy aging. We conducted a cross-sectional evaluation of white matter integrity, BMI, and vascular/inflammatory factors in a cohort of 138 healthy older adults (mean age: 71.3 years). Participants underwent diffusion tensor imaging, provided blood samples, and participated in a health evaluation. Vascular risk factors and vascular/inflammatory blood markers were assessed. The primary outcome measure was fractional anisotropy (FA) of the genu, body, and splenium (corpus callosum); exploratory measures included additional white matter regions, based on significant associations with BMI. Regression analyses indicated that higher BMI was associated with lower FA in the corpus callosum, cingulate, and fornix (p
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- 2013
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15. Cognitive processing speed in older adults: relationship with white matter integrity.
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Geoffrey A Kerchner, Caroline A Racine, Sandra Hale, Reva Wilheim, Victor Laluz, Bruce L Miller, and Joel H Kramer
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Medicine ,Science - Abstract
Cognitive processing slows with age. We sought to determine the importance of white matter integrity, assessed by diffusion tensor imaging (DTI), at influencing cognitive processing speed among normal older adults, assessed using a novel battery of computerized, non-verbal, choice reaction time tasks. We studied 131 cognitively normal adults aged 55-87 using a cross-sectional design. Each participant underwent our test battery, as well as MRI with DTI. We carried out cross-subject comparisons using tract-based spatial statistics. As expected, reaction time slowed significantly with age. In diffuse areas of frontal and parietal white matter, especially the anterior corpus callosum, fractional anisotropy values correlated negatively with reaction time. The genu and body of the corpus callosum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus were among the areas most involved. This relationship was not explained by gray or white matter atrophy or by white matter lesion volume. In a statistical mediation analysis, loss of white matter integrity mediated the relationship between age and cognitive processing speed.
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- 2012
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16. Physical activity measurement in older adults: Wearables versus self-report.
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Anna VandeBunte, Eva Gontrum, Lauren Goldberger, Corrina Fonseca, Nina Djukic, Michelle You, Joel H. Kramer, and Kaitlin B. Casaletto
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- 2022
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17. Sex Differences in the Relationship between Perceived Stress and Cognitive Trajectories
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Emily W, Paolillo, Michelle, You, Eva, Gontrum, Rowan, Saloner, Leslie S, Gaynor, Joel H, Kramer, and Kaitlin B, Casaletto
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Psychiatry and Mental health ,Geriatrics and Gerontology - Abstract
Chronic stress adversely affects cognition, in part due to stress-induced inflammation. Rodent models suggest females are more resilient against stress-related cognitive dysfunction than males; however, few studies have examined this in humans. We examined sex differences in the relationship between perceived stress, cognitive functioning, and peripheral inflammation over time among cognitively normal older adults.Longitudinal observational study.University research center.274 community-dwelling older adults (baseline age: M=70.7, SD=7.2; 58% women; Clinical Dementia Rating=0) who completed at least two study visits.Neurocognitive functioning and perceived stress (Perceived Stress Scale [PSS]) were assessed at each visit. Plasma was analyzed for interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in a subset of 147 participants. Linear mixed effects models examined the interaction between average PSS (i.e., averaged within persons across visits), sex, and time on cognitive domains and on inflammatory markers.The interaction between stress, sex, and time predicted executive functioning (β = 0.26, SE = 0.10, p = 0.01) such that higher average PSS related to steeper declines in men, but not in women. Among the 147 participants with inflammatory data, higher average PSS was associated with steeper increases in IL-6 over time in men, but not in women.Consistent with animal models, results showed older men were more vulnerable to negative effects of stress on cognitive aging, with domain-specific declines in executive function. Findings also suggest systemic immunological mechanisms may underlie increased risk for cognitive decline in men with higher levels of stress. Future work is needed to examine the potential efficacy of person-specific stress interventions.
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- 2023
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18. Semantic knowledge of social interactions is mediated by the hedonic evaluation system in the brain
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Myrthe G. Rijpma, Maxime Montembeault, Suzanne Shdo, Joel H. Kramer, Bruce L. Miller, and Katherine P. Rankin
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Neuropsychology and Physiological Psychology ,Cognitive Neuroscience ,Experimental and Cognitive Psychology - Published
- 2023
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19. Wearable Use in an Observational Study Among Older Adults: Adherence, Feasibility, and Effects of Clinicodemographic Factors.
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Emily W. Paolillo, Shannon Y. Lee, Anna VandeBunte, Nina Djukic, Corrina Fonseca, Joel H. Kramer, and Kaitlin B. Casaletto
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- 2022
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20. The Rapid Naming Test: Development and initial validation in typically aging adults
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Sabrina J. Erlhoff, Michelle You, Molly E. Zimmerman, Sladjana Lukic, Adam M. Staffaroni, Gil D. Rabinovici, Kaitlin B. Casaletto, Katherine L. Possin, Jordan Stiver, Renaud La Joie, Samantha M Walters, Joel H. Kramer, and Maria Luisa Gorno-Tempini
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medicine.medical_specialty ,Aging ,Amyloid beta-Peptides ,Reproducibility of Results ,Cognition ,Audiology ,Neuropsychological Tests ,Word finding ,Test (assessment) ,Psychiatry and Mental health ,Clinical Psychology ,Neuropsychology and Physiological Psychology ,Arts and Humanities (miscellaneous) ,Tip of the tongue ,Developmental and Educational Psychology ,Complaint ,medicine ,Humans ,Psychology ,Pathological ,Biomarkers ,Aged ,Language - Abstract
Progressive word-finding difficulty is a primary cognitive complaint among healthy older adults and a symptom of pathological aging. Classic measures of visual confrontation naming, however, show c...
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- 2023
21. Radiogenomics ofC9orf72Expansion Carriers Reveals Global Transposable Element Derepression and Enables Prediction of Thalamic Atrophy and Clinical Impairment
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Luke W. Bonham, Ethan G. Geier, Daniel W. Sirkis, Josiah K. Leong, Eliana Marisa Ramos, Qing Wang, Anna Karydas, Suzee E. Lee, Virginia E. Sturm, Russell P. Sawyer, Adit Friedberg, Justin K. Ichida, Aaron D. Gitler, Leo Sugrue, Michael Cordingley, Walter Bee, Eckard Weber, Joel H. Kramer, Katherine P. Rankin, Howard J. Rosen, Adam L. Boxer, William W. Seeley, John Ravits, Bruce L. Miller, and Jennifer S. Yokoyama
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General Neuroscience - Abstract
Hexanucleotide repeat expansion (HRE) withinC9orf72is the most common genetic cause of frontotemporal dementia (FTD). Thalamic atrophy occurs in both sporadic and familial FTD but is thought to distinctly affect HRE carriers. Separately, emerging evidence suggests widespread derepression of transposable elements (TEs) in the brain in several neurodegenerative diseases, includingC9orf72HRE-mediated FTD (C9-FTD). Whether TE activation can be measured in peripheral blood and how the reduction in peripheralC9orf72expression observed in HRE carriers relates to atrophy and clinical impairment remain unknown. We used FreeSurfer software to assess the effects ofC9orf72HRE and clinical diagnosis (n= 78 individuals, male and female) on atrophy of thalamic nuclei. We also generated a novel, human, whole-blood RNA-sequencing dataset to determine the relationships among peripheralC9orf72expression, TE activation, thalamic atrophy, and clinical severity (n= 114 individuals, male and female). We confirmed global thalamic atrophy and reducedC9orf72expression in HRE carriers. Moreover, we identified disproportionate atrophy of the right mediodorsal lateral nucleus in HRE carriers and showed thatC9orf72expression associated with clinical severity, independent of thalamic atrophy. Strikingly, we found global peripheral activation of TEs, including the human endogenous LINE-1 elementL1HS.L1HSlevels were associated with atrophy of multiple pulvinar nuclei, a thalamic region implicated in C9-FTD. Integration of peripheral transcriptomic and neuroimaging data from human HRE carriers revealed atrophy of specific thalamic nuclei, demonstrated thatC9orf72levels relate to clinical severity, and identified marked derepression of TEs, includingL1HS, which predicted atrophy of FTD-relevant thalamic nuclei.SIGNIFICANCE STATEMENTPathogenic repeat expansion inC9orf72is the most frequent genetic cause of FTD and amyotrophic lateral sclerosis (ALS; C9-FTD/ALS). The clinical, neuroimaging, and pathologic features of C9-FTD/ALS are well characterized, whereas the intersections of transcriptomic dysregulation and brain structure remain largely unexplored. Herein, we used a novel radiogenomic approach to examine the relationship between peripheral blood transcriptomics and thalamic atrophy, a neuroimaging feature disproportionately impacted in C9-FTD/ALS. We confirmed reduction ofC9orf72in blood and found broad dysregulation of transposable elements—genetic elements typically repressed in the human genome—in symptomaticC9orf72expansion carriers, which associated with atrophy of thalamic nuclei relevant to FTD.C9orf72expression was also associated with clinical severity, suggesting that peripheralC9orf72levels capture disease-relevant information.
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- 2022
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22. Feasibility and Acceptability of a Multidisciplinary Academic Telemedicine System for Memory Care in Response to COVID-19
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James Fraser Rini, Elena Tsoy, Bradley Peet, John Best, Jeremy A. Tanner, Breton M. Asken, Alejandra Sanchez, Alexandra C. Apple, Lawren VandeVrede, Melanie L. Stephens, Michael Erkkinen, Joel H. Kramer, and Bruce L. Miller
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Aging ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,8.1 Organisation and delivery of services ,Health Services ,Neurodegenerative ,Alzheimer's Disease ,Brain Disorders ,Good Health and Well Being ,Clinical Research ,Acquired Cognitive Impairment ,Dementia ,Neurology (clinical) ,Research Article ,Health and social care services research - Abstract
Background and ObjectivesIn response to the restrictions imposed by the COVID-19 pandemic, the University of California San Francisco Memory and Aging Center (UCSF MAC) has deployed a comprehensive telemedicine model for the diagnosis and management of Alzheimer disease and related dementias. This review summarizes a large academic behavioral neurology clinic's experience transitioning to telemedicine services, including the impact on clinic care indicators, access metrics, and provider's experience. We compared these outcomes from 3 years before COVID-19 to 12 months after the transition to video teleconferencing (VTC) encounters.MethodsPatient demographics and appointment data (dates, visit types, and departments) were extracted from our institution's electronic health record database from January 1, 2017, to May 1, 2021. We present data as descriptive statistics and comparisons using Wilcoxon rank-sum tests and Fisher exact tests. The results of anonymous surveys conducted among the clinic's providers are reported as descriptive findings.ResultsAfter the implementation of telemedicine services, the proportion of clinic encounters completed via VTC increased from 1.9% to 86.4%. There was a statistically significant decline in both the percentage of scheduled appointments that were canceled (32.9% vs 27.9%;p< 0.01) and total cancelations per month (mean 240.3 vs 179.4/mo;p< 0.01). There was an increase in the percentage of completed scheduled appointments (60.2% vs 64.8%;p< 0.01) and an increase in the average estimated commuting distance patients would need to drive for follow-up appointments (mean 49.8 vs 54.7 miles;p< 0.01). The transition to telemedicine services did not significantly affect the clinic's patient population as measured by age, gender, estimated income, area deprivation index, or self-reported racial/ethnic identity. The results of the provider survey revealed that physicians reported a more positive experience relative to neuropsychologists. Both types of providers reported telemedicine services as a reasonable equivalent and acceptable alternative to in-person evaluations with notable caveats.DiscussionUCSF MAC's comprehensive integration of telemedicine services maintained critical ambulatory care to patients living with dementia during the COVID-19 pandemic. The recognized benefits of our care model suggest dementia telemedicine may be used as a feasible and equivalent alternative to in-person ambulatory care in the after COVID-19 era.
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- 2022
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23. Big smile, small self: Awe walks promote prosocial positive emotions in older adults
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Dacher Keltner, Christina R. Veziris, Eena L. Kosik, Joel H. Kramer, Nathaniel A. Morris, Isabel J. Sible, Ashlin R. K. Roy, Sarah R. Holley, Virginia E. Sturm, Bruce L. Miller, Samir Datta, John Neuhaus, and Tiffany E Chow
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media_common.quotation_subject ,Emotions ,Context (language use) ,Anxiety ,Smiling ,050105 experimental psychology ,Article ,Developmental psychology ,Sadness ,medicine ,Humans ,0501 psychology and cognitive sciences ,General Psychology ,media_common ,Aged ,05 social sciences ,Life satisfaction ,Anxiety Disorders ,Social relation ,Distress ,Prosocial behavior ,Sympathy ,medicine.symptom ,Psychology ,human activities - Abstract
Aging into later life is often accompanied by social disconnection, anxiety, and sadness. Negative emotions are self-focused states with detrimental effects on aging and longevity. Awe-a positive emotion elicited when in the presence of vast things not immediately understood-reduces self-focus, promotes social connection, and fosters prosocial actions by encouraging a "small self." We investigated the emotional benefits of a novel "awe walk" intervention in healthy older adults. Sixty participants took weekly 15-min outdoor walks for 8 weeks; participants were randomly assigned to an awe walk group, which oriented them to experience awe during their walks, or to a control walk group. Participants took photographs of themselves during each walk and rated their emotional experience. Each day, they reported on their daily emotional experience outside of the walk context. Participants also completed pre- and postintervention measures of anxiety, depression, and life satisfaction. Compared with participants who took control walks, those who took awe walks experienced greater awe during their walks and exhibited an increasingly "small self" in their photographs over time. They reported greater joy and prosocial positive emotions during their walks and displayed increasing smile intensity over the study. Outside of the walk context, participants who took awe walks reported greater increases in daily prosocial positive emotions and greater decreases in daily distress over time. Postintervention anxiety, depression, and life satisfaction did not change from baseline in either group. These results suggest cultivating awe enhances positive emotions that foster social connection and diminishes negative emotions that hasten decline. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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- 2023
24. Amyloid, tau and metabolic PET correlates of cognition in early and late-onset Alzheimer’s disease
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Jeremy A Tanner, Leonardo Iaccarino, Lauren Edwards, Breton M Asken, Maria L Gorno-Tempini, Joel H Kramer, Julie Pham, David C Perry, Katherine Possin, Maura Malpetti, Taylor Mellinger, Bruce L Miller, Zachary Miller, Nidhi S Mundada, Howard J Rosen, David N Soleimani-Meigooni, Amelia Strom, Renaud La Joie, and Gil D Rabinovici
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Original Article ,Neurology (clinical) - Abstract
Early-onset (age < 65) Alzheimer’s disease is associated with greater non-amnestic cognitive symptoms and neuropathological burden than late-onset disease. It is not fully understood whether these groups also differ in the associations between molecular pathology, neurodegeneration and cognitive performance. We studied amyloid-positive patients with early-onset (n = 60, mean age 58 ± 4, MMSE 21 ± 6, 58% female) and late-onset (n = 53, mean age 74 ± 6, MMSE 23 ± 5, 45% female) Alzheimer’s disease who underwent neurological evaluation, neuropsychological testing, 11C-Pittsburgh compound B PET (amyloid-PET) and 18F-flortaucipir PET (tau-PET). 18F-fluorodeoxyglucose PET (brain glucose metabolism PET) was also available in 74% (n = 84) of participants. Composite scores for episodic memory, semantic memory, language, executive function and visuospatial domains were calculated based on cognitively unimpaired controls. Voxel-wise regressions evaluated correlations between PET biomarkers and cognitive scores and early-onset versus late-onset differences were tested with a PET × Age group interaction. Mediation analyses estimated direct and indirect (18F-fluorodeoxyglucose mediated) local associations between 18F-flortaucipir binding and cognitive scores in domain-specific regions of interest. We found that early-onset patients had higher 18F-flortaucipir binding in parietal, lateral temporal and lateral frontal cortex; more severe 18F-fluorodeoxyglucose hypometabolism in the precuneus and angular gyrus; and greater 11C-Pittsburgh compound B binding in occipital regions compared to late-onset patients. In our primary analyses, PET–cognition correlations did not meaningfully differ between age groups.18F-flortaucipir and 18F-fluorodeoxyglucose, but not 11C-Pittsburgh compound B, were significantly associated with cognition in expected domain-specific patterns in both age groups (e.g. left perisylvian/language, frontal/executive, occipital/visuospatial). 18F-fluorodeoxyglucose mediated the relationship between 18F-flortaucipir and cognition in both age groups across all domains except episodic memory in late-onset patients. Additional direct effects of 18F-flortaucipir were observed for executive function in all age groups, language in early-onset Alzheimer’s disease and in the total sample and visuospatial function in the total sample. In conclusion, tau and neurodegeneration, but not amyloid, were similarly associated with cognition in both early and late-onset Alzheimer’s disease. Tau had an association with cognition independent of neurodegeneration in language, executive and visuospatial functions in the total sample. Our findings support tau PET as a biomarker that captures both the clinical severity and molecular pathology specific to Alzheimer’s disease across the broad spectrum of ages and clinical phenotypes in Alzheimer’s disease.
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- 2022
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25. New insights into the genetic etiology of Alzheimer's disease and related dementias
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Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. A., Piñol-Ripoll, G., Pisanu, C., Polak, T., Popp, J., Posthuma, D., Priller, J., Puerta, R., Quenez, O., Quintela, I., Thomassen, J. Q., Rábano, A., Rainero, I., Rajabli, F., Ramakers, I., Real, L. M., Reinders, M. J. T., Reitz, C., Reyes-Dumeyer, D., Ridge, P., Riedel-Heller, S., Riederer, P., Roberto, N., Rodriguez-Rodriguez, E., Rongve, A., Allende, I. R., Rosende-Roca, M., Royo, J. L., Rubino, E., Rujescu, D., Sáez, M. E., Sakka, P., Saltvedt, I., Sanabria, Á., Sánchez-Arjona, M. B., Sanchez-Garcia, F., Juan, P. S., Sánchez-Valle, R., Sando, S. B., Sarnowski, C., Satizabal, C. L., Scamosci, M., Scarmeas, N., Scarpini, E., Scheltens, P., Scherbaum, N., Scherer, M., Schmid, M., Schneider, A., Schott, J. M., Selbæk, G., Seripa, D., Serrano, M., Sha, J., Shadrin, A. A., Skrobot, O., Slifer, S., Snijders, G. J. L., Soininen, H., Solfrizzi, V., Solomon, A., Song, Y. E., Sorbi, S., Sotolongo-Grau, O., Spalletta, G., Spottke, A., Squassina, A., Stordal, E., Tartan, J. P., Tárraga, L., Tesí, N., Thalamuthu, A., Thomas, T., Tosto, G., Traykov, L., Tremolizzo, L., Tybjærg-Hansen, A., Uitterlinden, A., Ullgren, A., Ulstein, I., Valero, S., Valladares, O., Broeckhoven, C. V., Vance, J., Vardarajan, B. N., van der Lugt, A., Dongen, J. V., van Rooij, J., van Swieten, J., Vandenberghe, R., Verhey, F., Vidal, J. -S., Vogelgsang, J., Vyhnalek, M., Wagner, M., Wallon, D., Wang, L. -S., Wang, R., Weinhold, L., Wiltfang, J., Windle, G., Woods, B., Yannakoulia, M., Zare, H., Zhao, Y., Zhang, X., Zhu, C., Zulaica, M., Laczo, J., Matoska, V., Serpente, M., Assogna, F., Piras, F., Ciullo, V., Shofany, J., Ferrarese, C., Andreoni, S., Sala, G., Zoia, C. P., Zompo, M. D., Benussi, A., Bastiani, P., Takalo, M., Natunen, T., Laatikainen, T., Tuomilehto, J., Antikainen, R., Strandberg, T., Lindström, J., Peltonen, M., Abraham, R., Al-Chalabi, A., Bass, N. J., Brayne, C., Brown, K. S., Collinge, J., Craig, D., Deloukas, P., Fox, N., Gerrish, A., Gill, M., Gwilliam, R., Harold, D., Hollingworth, P., Johnston, J. A., Jones, L., Lawlor, B., Livingston, G., Lovestone, S., Lupton, M., Lynch, A., Mann, D., Mcguinness, B., Mcquillin, A., O’Donovan, M. C., Owen, M. J., Passmore, P., Powell, J. F., Proitsi, P., Rossor, M., Shaw, C. E., Smith, A. D., Gurling, H., Todd, S., Mummery, C., Ryan, N., Lacidogna, G., Adarmes-Gómez, A., Mauleón, A., Pancho, A., Gailhajenet, A., Lafuente, A., Macias-García, D., Martín, E., Pelejà, E., Carrillo, F., Merlín, I. S., Garrote-Espina, L., Vargas, L., Carrion-Claro, M., Marín, M., Labrador, M., Buendia, M., Alonso, M. D., Guitart, M., Moreno, M., Ibarria, M., Periñán, M., Aguilera, N., Gómez-Garre, P., Cañabate, P., Escuela, R., Pineda-Sánchez, R., Vigo-Ortega, R., Jesús, S., Preckler, S., Rodrigo-Herrero, S., Diego, S., Vacca, A., Roveta, F., Salvadori, N., Chipi, E., Boecker, H., Laske, C., Perneczky, R., Anastasiou, C., Janowitz, D., Malik, R., Anastasiou, A., Parveen, K., López-García, S., Antonell, A., Mihova, K. Y., Belezhanska, D., Weber, H., Kochen, S., Solis, P., Medel, N., Lisso, J., Sevillano, Z., Politis, D. G., Cores, V., Cuesta, C., Ortiz, C., Bacha, J. I., Rios, M., Saenz, A., Abalos, M. S., Kohler, E., Palacio, D. L., Etchepareborda, I., Kohler, M., Novack, G., Prestia, F. A., Galeano, P., Castaño, E. M., Germani, S., Toso, C. R., Rojo, M., Ingino, C., Mangone, C., Rubinsztein, D. C., Teipel, S., Fievet, N., Deramerourt, V., Forsell, C., Thonberg, H., Bjerke, M., Roeck, E. D., Martínez-Larrad, M. T., Olivar, N., Cano, A., Macias, J., Maroñas, O., Nuñez-Llaves, R., Olivé, C., Adarmes-Gómez, A. D., Amer-Ferrer, G., Antequera, M., Burguera, J. A., Casajeros, M. J., Martinez de Pancorbo, M., Hevilla, S., Espinosa, M. A. L., Legaz, A., Manzanares, S., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, V., Martínez-Lage Álvarez, P., Iriarte, M. M., Periñán-Tocino, M. T., Real de Asúa, D., Rodrigo, S., Sastre, I., Vicente, M. P., Vivancos, L., Epelbaum, J., Hannequin, D., Campion, D., Deramecourt, V., Tzourio, C., Brice, A., Dubois, B., Williams, A., Thomas, C., Davies, C., Nash, W., Dowzell, K., Morales, A. C., Bernardo-Harrington, M., Turton, J., Lord, J., Brown, K., Vardy, E., Fisher, E., Warren, J. D., Ryan, N. S., Guerreiro, R., Uphill, J., Bass, N., Heun, R., Kölsch, H., Schürmann, B., Lacour, A., Herold, C., Powell, J., Patel, Y., Hodges, A., Becker, T., Warden, D., Wilcock, G., Clarke, R., Ben-Shlomo, Y., Hooper, N. M., Pickering-Brown, S., Sussams, R., Warner, N., Bayer, A., Heuser, I., Drichel, D., Klopp, N., Mayhaus, M., Riemenschneider, M., Pinchler, S., Feulner, T., Gu, W., van den Bussche, H., Hüll, M., Frölich, L., Wichmann, H. -E., Jöckel, K. -H., O’Donovan, M., Owen, M., Bahrami, S., Bosnes, I., Selnes, P., Bergh, S., Palotie, A., Daly, M., Jacob, H., Matakidou, A., Runz, H., John, S., Plenge, R., Mccarthy, M., Hunkapiller, J., Ehm, M., Waterworth, D., Fox, C., Malarstig, A., Klinger, K., Call, K., Behrens, T., Loerch, P., Mäkelä, T., Kaprio, J., Virolainen, P., Pulkki, K., Kilpi, T., Perola, M., Partanen, J., Pitkäranta, A., Kaarteenaho, R., Vainio, S., Turpeinen, M., Serpi, R., Laitinen, T., Mäkelä, J., Kosma, V. -M., Kujala, U., Tuovila, O., Hendolin, M., Pakkanen, R., Waring, J., Riley-Gillis, B., Liu, J., Biswas, S., Diogo, D., Marshall, C., Hu, X., Gossel, M., Graham, R., Cummings, B., Ripatti, S., Schleutker, J., Arvas, M., Carpén, O., Hinttala, R., Kettunen, J., Mannermaa, A., Laukkanen, J., Julkunen, V., Remes, A., Kälviäinen, R., Peltola, J., Tienari, P., Rinne, J., Ziemann, A., Esmaeeli, S., Smaoui, N., Lehtonen, A., Eaton, S., Lahdenperä, S., van Adelsberg, J., Michon, J., Kerchner, G., Bowers, N., Teng, E., Eicher, J., Mehta, V., Gormley, P., Linden, K., Whelan, C., Xu, F., Pulford, D., Färkkilä, M., Pikkarainen, S., Jussila, A., Blomster, T., Kiviniemi, M., Voutilainen, M., Georgantas, B., Heap, G., Rahimov, F., Usiskin, K., Lu, T., Oh, D., Kalpala, K., Miller, M., Mccarthy, L., Eklund, K., Palomäki, A., Isomäki, P., Pirilä, L., Kaipiainen-Seppänen, O., Huhtakangas, J., Lertratanakul, A., Hochfeld, M., Bing, N., Gordillo, J. E., Mars, N., Pelkonen, M., Kauppi, P., Kankaanranta, H., Harju, T., Close, D., Greenberg, S., Chen, H., Betts, J., Ghosh, S., Salomaa, V., Niiranen, T., Juonala, M., Metsärinne, K., Kähönen, M., Junttila, J., Laakso, M., Pihlajamäki, J., Sinisalo, J., Taskinen, M. -R., Tuomi, T., Challis, B., Peterson, A., Chu, A., Parkkinen, J., Muslin, A., Joensuu, H., Meretoja, T., Aaltonen, L., Mattson, J., Auranen, A., Karihtala, P., Kauppila, S., Auvinen, P., Elenius, K., Popovic, R., Schutzman, J., Loboda, A., Chhibber, A., Lehtonen, H., Mcdonough, S., Crohns, M., Kulkarni, D., Kaarniranta, K., Turunen, J. A., Ollila, T., Seitsonen, S., Uusitalo, H., Aaltonen, V., Uusitalo-Järvinen, H., Luodonpää, M., Hautala, N., Loomis, S., Strauss, E., Podgornaia, A., Hoffman, J., Tasanen, K., Huilaja, L., Hannula-Jouppi, K., Salmi, T., Peltonen, S., Koulu, L., Harvima, I., Wu, Y., Choy, D., Pussinen, P., Salminen, A., Salo, T., Rice, D., Nieminen, P., Palotie, U., Siponen, M., Suominen, L., Mäntylä, P., Gursoy, U., Anttonen, V., Sipilä, K., Davis, J. W., Quarless, D., Petrovski, S., Wigmore, E., Chen, C. -Y., Bronson, P., Tsai, E., Huang, Y., Maranville, J., Shaikho, E., Mohammed, E., Wadhawan, S., Kvikstad, E., Caliskan, M., Chang, D., Bhangale, T., Pendergrass, S., Holzinger, E., Chen, X., Hedman, Å., King, K. S., Wang, C., Xu, E., Auge, F., Chatelain, C., Rajpal, D., Liu, D., Xia, T. -H., Brauer, M., Kurki, M., Karjalainen, J., Havulinna, A., Jalanko, A., Palta, P., della Briotta Parolo, P., Zhou, W., Lemmelä, S., Rivas, M., Harju, J., Lehisto, A., Ganna, A., Llorens, V., Laivuori, H., Rüeger, S., Niemi, M. E., Tukiainen, T., Reeve, M. P., Heyne, H., Palin, K., Garcia-Tabuenca, J., Siirtola, H., Kiiskinen, T., Lee, J., Tsuo, K., Elliott, A., Kristiansson, K., Hyvärinen, K., Ritari, J., Koskinen, M., Pylkäs, K., Kalaoja, M., Karjalainen, M., Mantere, T., Kangasniemi, E., Heikkinen, S., Laakkonen, E., Sipeky, C., Heron, S., Karlsson, A., Jambulingam, D., Rathinakannan, V. S., Kajanne, R., Aavikko, M., Jiménez, M. G., della Briotta Parola, P., Kanai, M., Kaunisto, M., Kilpeläinen, E., Sipilä, T. 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Kathleen, A Welsh-Bohmer, Patrice, L Whitehead, Ellen, M Wijsman, Kirk, C Wilhelmsen, Benjamin, Williams, Jennifer, Williamson, Henrik, Wilms, Thomas, S Wingo, Thomas, Wisniewski, Randall, L Woltjer, Martin, Woon, Clinton, B Wright, Chuang-Kuo, Wu, Steven, G Younkin, Chang-En, Yu, Lei, Yu, Yuanchao, Zhang, Zhao, Yi, Xiongwei, Zhu, Hieab, Adams, Rufus, O Akinyemi, Muhammad, Ali, Nicola, Armstrong, Hugo, J Aparicio, Maryam, Bahadori, Monique, Breteler, Daniel, Chasman, Ganesh, Chauhan, Hata, Comic, Simon, Cox, Adrienne, L Cupples, Gail, Davies, Charles, S DeCarli, Marie-Gabrielle, Duperron, Josée, Dupuis, Tavia, Evans, Frank, Fan, Annette, Fitzpatrick, Alison, E Fohner, Mary, Ganguli, Mirjam, Geerlings, Stephen, J Glatt, Hector, M Gonzalez, Monica, Goss, Hans, Grabe, Mohamad, Habes, Susan, R Heckbert, Edith, Hofer, Elliot, Hong, Timothy, Hughes, Tiffany, F Kautz, Maria, Knol, William, Kremen, Paul, Lacaze, Jari, Lahti, Quentin Le Grand, Elizabeth, Litkowski, Shuo, Li, Dan, Liu, Xuan, Liu, Marisa, Loitfelder, Alisa, Manning, Pauline, Maillard, Riccardo, Marioni, Bernard, Mazoyer, Debora Melo van Lent, Hao, Mei, Aniket, Mishra, Paul, Nyquist, Jeffrey, O'Connell, Yash, Patel, Tomas, Paus, Zdenka, Pausova, Katri, Raikkonen-Talvitie, Moeen, Riaz, Stephen, Rich, Jerome, Rotter, Jose, Romero, Gena, Roshchupkin, Yasaman, Saba, Murali, Sargurupremraj, Helena, Schmidt, Reinhold, Schmidt, Joshua, M Shulman, Jennifer, Smith, Hema, Sekhar, Reddy, Rajula, Jean, Shin, Jeannette, Simino, Eeva, Sliz, Alexander, Teumer, Alvin, Thomas, Adrienne, Tin, Elliot, Tucker-Drob, Dina, Vojinovic, Yanbing, Wang, Galit, Weinstein, Dylan, Williams, Katharina, Wittfeld, Lisa, Yanek, Yunju, Yang, Bellenguez, C, Küçükali, F, Jansen, I, Kleineidam, L, Moreno-Grau, S, Amin, N, Naj, A, Campos-Martin, R, Grenier-Boley, B, Andrade, V, Holmans, P, Boland, A, Damotte, V, van der Lee, S, Costa, M, Kuulasmaa, T, Yang, Q, de Rojas, I, Bis, J, Yaqub, A, Prokic, I, Chapuis, J, Ahmad, S, Giedraitis, V, 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M, Rossi, P, Djurovic, S, Duron, E, Düzel, E, Dufouil, C, Eiriksdottir, G, Engelborghs, S, Escott-Price, V, Espinosa, A, Ewers, M, Faber, K, Fabrizio, T, Nielsen, S, Fardo, D, Farotti, L, Fenoglio, C, Fernández-Fuertes, M, Ferrari, R, Ferreira, C, Ferri, E, Fin, B, Fischer, P, Fladby, T, Fließbach, K, Fongang, B, Fornage, M, Fortea, J, Foroud, T, Fostinelli, S, Fox, N, Franco-Macías, E, Bullido, M, Frank-García, A, Froelich, L, Fulton-Howard, B, Galimberti, D, García-Alberca, J, García-González, P, Garcia-Madrona, S, Garcia-Ribas, G, Ghidoni, R, Giegling, I, Giorgio, G, Goate, A, Goldhardt, O, Gomez-Fonseca, D, González-Pérez, A, Graff, C, Grande, G, Green, E, Grimmer, T, Grünblatt, E, Grunin, M, Gudnason, V, Guetta-Baranes, T, Haapasalo, A, Hadjigeorgiou, G, Haines, J, Hamilton-Nelson, K, Hampel, H, Hanon, O, Hardy, J, Hartmann, A, Hausner, L, Harwood, J, Heilmann-Heimbach, S, Helisalmi, S, Heneka, M, Hernández, I, Herrmann, M, Hoffmann, P, Holmes, C, Holstege, H, Vilas, R, Hulsman, M, Humphrey, J, Biessels, G, Jian, X, Johansson, C, Jun, G, Kastumata, Y, Kauwe, J, Kehoe, P, Kilander, L, Ståhlbom, A, Kivipelto, M, Koivisto, A, Kornhuber, J, Kosmidis, M, Kukull, W, Kuksa, P, Kunkle, B, Kuzma, A, Lage, C, Laukka, E, Launer, L, Lauria, A, Lee, C, Lehtisalo, J, Lerch, O, Lleó, A, Longstreth, W, Lopez, O, de Munain, A, Love, S, Löwemark, M, Luckcuck, L, Lunetta, K, Ma, Y, Macías, J, Macleod, C, Maier, W, Mangialasche, F, Spallazzi, M, Marquié, M, Marshall, R, Martin, E, Montes, A, Rodríguez, C, Masullo, C, Mayeux, R, Mead, S, Mecocci, P, Medina, M, Meggy, A, Mehrabian, S, Mendoza, S, Menéndez-González, M, Mir, P, Moebus, S, Mol, M, Molina-Porcel, L, Montrreal, L, Morelli, L, Moreno, F, Morgan, K, Mosley, T, Nöthen, M, Muchnik, C, Mukherjee, S, Nacmias, B, Ngandu, T, Nicolas, G, Nordestgaard, B, Olaso, R, Orellana, A, Orsini, M, Ortega, G, Padovani, A, Paolo, C, Papenberg, G, Parnetti, L, Pasquier, F, Pastor, P, Peloso, G, Pérez-Cordón, A, Pérez-Tur, J, Pericard, P, Peters, O, Pijnenburg, Y, Pineda, J, Piñol-Ripoll, G, Pisanu, C, Polak, T, Popp, J, Posthuma, D, Priller, J, Puerta, R, Quenez, O, Quintela, I, Thomassen, J, Rábano, A, Rainero, I, Rajabli, F, Ramakers, I, Real, L, Reinders, M, Reitz, C, Reyes-Dumeyer, D, Ridge, P, Riedel-Heller, S, Riederer, P, Roberto, N, Rodriguez-Rodriguez, E, Rongve, A, Allende, I, Rosende-Roca, M, Royo, J, Rubino, E, Rujescu, D, Sáez, M, Sakka, P, Saltvedt, I, Sanabria, Á, Sánchez-Arjona, M, Sanchez-Garcia, F, Juan, P, Sánchez-Valle, R, Sando, S, Sarnowski, C, Satizabal, C, Scamosci, M, Scarmeas, N, Scarpini, E, Scheltens, P, Scherbaum, N, Scherer, M, Schmid, M, Schneider, A, Schott, J, Selbæk, G, Seripa, D, Serrano, M, Sha, J, Shadrin, A, Skrobot, O, Slifer, S, Snijders, G, Soininen, H, Solfrizzi, V, Solomon, A, Song, Y, Sorbi, S, Sotolongo-Grau, O, Spalletta, G, Spottke, A, Squassina, A, Stordal, E, Tartan, J, Tárraga, L, Tesí, N, Thalamuthu, A, Thomas, T, Tosto, G, Traykov, L, Tremolizzo, L, Tybjærg-Hansen, A, Uitterlinden, A, Ullgren, A, Ulstein, I, Valero, S, Valladares, O, Broeckhoven, C, Vance, J, Vardarajan, B, van der Lugt, A, Dongen, J, van Rooij, J, van Swieten, J, Vandenberghe, R, Verhey, F, Vidal, J, Vogelgsang, J, Vyhnalek, M, Wagner, M, Wallon, D, Wang, L, Wang, R, Weinhold, L, Wiltfang, J, Windle, G, Woods, B, Yannakoulia, M, Zare, H, Zhao, Y, Zhang, X, Zhu, C, Zulaica, M, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Farrer, L, Psaty, B, Ghanbari, M, Raj, T, Sachdev, P, Mather, K, Jessen, F, Ikram, M, de Mendonça, A, Hort, J, Tsolaki, M, Pericak-Vance, M, Amouyel, P, Williams, J, Frikke-Schmidt, R, Clarimon, J, Deleuze, J, Rossi, G, Seshadri, S, Andreassen, O, Ingelsson, M, Hiltunen, M, Sleegers, K, Schellenberg, G, van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, VU University medical center, Amsterdam Neuroscience - Neurodegeneration, Neurology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, 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Sachdev, Perminder [0000-0002-9595-3220], Mather, Karen [0000-0003-4143-8941], Ikram, M Arfan [0000-0003-0372-8585], Tsolaki, Magda [0000-0002-2072-8010], Pericak-Vance, Margaret A [0000-0001-7283-8804], Amouyel, Philippe [0000-0001-9088-234X], Williams, Julie [0000-0002-4069-0259], Frikke-Schmidt, Ruth [0000-0003-4084-5027], Seshadri, Sudha [0000-0001-6135-2622], Andreassen, Ole A [0000-0002-4461-3568], Sleegers, Kristel [0000-0002-0283-2332], van Duijn, Cornelia M [0000-0002-2374-9204], Sims, Rebecca [0000-0002-3885-1199], van der Flier, Wiesje M [0000-0001-8766-6224], Ramirez, Alfredo [0000-0003-4991-763X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Complex Trait Genetics, Clinical sciences, Neuroprotection & Neuromodulation, Pathologic Biochemistry and Physiology, Clinical Biology, Epidemiology, Internal Medicine, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
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tau Proteins/genetics ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurologi ,MED/03 - GENETICA MEDICA ,45/43 ,Medizin ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,genetics [Alzheimer Disease] ,Genome-Wide Association Study ,Humans ,tau Proteins ,Alzheimer Disease ,Cognitive Dysfunction ,VARIANTS ,pathology [Alzheimer Disease] ,Tau Proteins ,Settore BIO/13 - Biologia Applicata ,Cognitive Dysfunction/psychology ,692/699/375/365/1283 ,IMPUTATION ,article ,1184 Genetics, developmental biology, physiology ,Biología y Biomedicina / Biología ,AMYLOID-BETA ,Settore MED/26 - NEUROLOGIA ,Neurology ,psychology [Cognitive Dysfunction] ,Medical Genetics ,Human ,Neuroscience(all) ,631/208/205/2138 ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,ddc:570 ,Genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Medicinsk genetik ,MED/26 - NEUROLOGIA ,Alzheimer Disease/genetics ,neurology ,tau Protein ,NECROSIS-FACTOR-ALPHA ,RISK LOCI ,genetics [tau Proteins] ,PREDICTION MODELS ,Human medicine ,GENERATION ,RESPONSES - Abstract
25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
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- 2022
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26. Outcome measures for Alzheimer's disease:A global inter-societal Delphi consensus
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Tim S. Ellison, Stefano F. Cappa, Dawne Garrett, Jean Georges, Takeshi Iwatsubo, Joel H. Kramer, Maryna Lehmann, Constantine Lyketsos, Andrea B. Maier, Jennifer Merrilees, John C. Morris, Sharon L. Naismith, Flavio Nobili, Marco Pahor, Dimity Pond, Louise Robinson, Pinar Soysal, Mathieu Vandenbulcke, Christopher J. Weber, Pieter Jelle Visser, Michael Weiner, Giovanni B. Frisoni, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Psychology 6
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MILD COGNITIVE IMPAIRMENT ,Epidemiology ,Health Policy ,measures ,Alzheimer's disease ,outcomes ,Delphi ,FUNCTIONAL-ACTIVITIES QUESTIONNAIRE ,DEPRESSION SCALE ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,NEUROPSYCHIATRIC INVENTORY ,CORNELL SCALE ,Developmental Neuroscience ,consensus ,QUALITY-OF-LIFE ,DAILY LIVING SCALE ,Neurology (clinical) ,Geriatrics and Gerontology ,OLDER-ADULTS ,INSTRUMENTAL-ACTIVITIES ,dementia ,REVISED ACE-R - Abstract
Introduction: We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome. Methods: A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria. Results: Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes. Discussion: This work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine.
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- 2023
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27. Neurophysiological trajectories in Alzheimer’s disease progression
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Kiwamu Kudo, Kamalini G. Ranasinghe, Hirofumi Morise, Faatimah Syed, Kensuke Sekihara, Katherine P. Rankin, Bruce L. Miller, Joel H. Kramer, Gil D. Rabinovici, Keith Vossel, Heidi E. Kirsch, and Srikantan S. Nagarajan
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Article - Abstract
Alzheimer’s disease (AD) is characterized by accumulation of amyloid-βand misfolded tau proteins causing synaptic dysfunction and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relation to neurodegeneration and cognitive decline are unknown. We deployed robust event-based sequencing models (EBM) to investigate trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. Synchrony increases in delta-theta and decreases in alpha and beta bands showed progressive changes along the EBM stages of AD. Decreases in alpha and beta synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. Long-range synchrony effects were larger than local synchrony, indicating greater sensitivity of connectivity metrics involving multiple brain regions. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.
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- 2023
28. Clinical dimensions along the progressive nonfluent variant primary progressive aphasia spectrum
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Ignacio Illán-Gala, Diego L. Lorca-Puls, Zoe Ezzes, Jessica Deleon, Zachary A. Miller, Sara Rubio-Guerra, Miguel Santos-Santos, David Gómez-Andrés, Lea T. Grinberg, Salvatore Spina, Joel H. Kramer, Lisa Wauters, Maya L. Henry, Bruce L. Miller, William W. Seeley, Maria Luisa Mandelli, and Maria Luisa Gorno-Tempini
- Abstract
It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum traditionally termed nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analyzed speech, language, and disease severity features in a comprehensive cohort of patients with a progressive motor speech impairment and/or agrammatism to ascertain any evidence of the existence of naturally occurring, non-overlapping syndromic entities (e.g., PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with etiologic/prognostic value could be identified. We included 98 participants with progressive motor speech impairment and/or agrammatism, with 43 having an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating sum-of-boxes (CDR-SB). We investigated the data’s clustering tendency to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated utilizing linear mixed-effects models. Of the participants included in this study, 91 conformed to previously reported clinical profiles (69 with AOS and agrammatism, 18 PPAOS, and 4 PAA). The remaining seven participants were characterized by nonfluent speech and dysarthria without apraxia of speech or agrammatism. No baseline clinical features differentiated between FTLD neuropathological subgroups. Critically, the Hopkins statistic dismissed the presence of non-overlapping syndromic clusters in the entire sample (.45 with values near 0.5 indicating random data). Three data-driven components accounted for 71% of the variance ([i] severity-agrammatism, [ii] prominent AOS, and [iii] prominent dysarthria). The component typified by prominent dysarthria was more specific to patients with Progressive Supranuclear Palsy (4/5 [80%] participants with autopsy in this group had PSP), while the severity-agrammatism component predicted a faster CDR-SB increase. Higher dysarthria severity, reduced words per minute, and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression (as measured by the CDR-SB score). Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum strongly predictive of underlying Frontotemporal Lobar Degeneration (FTLD, 66% 4R tauopathy, 16% Pick’s disease, 9.3% FTLD TDP type A, and 12% other pathologies). While highlighting the graded distinctions (rather than sharp boundaries) that characterize the nfvPPA spectrum may be useful for establishing early clinical rehabilitation strategies, novel clinical and biological markers are needed to improve clinical-pathological correlations.
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- 2023
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29. Sex‐specific effects of SNAP‐25 genotype on verbal memory and Alzheimer's disease biomarkers in clinically normal older adults
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Rowan Saloner, Emily W. Paolillo, Kevin J. Wojta, Corrina Fonseca, Eva Q. Gontrum, Argentina Lario‐Lago, Gil D. Rabinovici, Jennifer S. Yokoyama, Jessica E. Rexach, Joel H. Kramer, and Kaitlin B. Casaletto
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2023
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30. Immune cell counts in cerebrospinal fluid predict cognitive function in aging and neurodegenerative disease
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Allison Snyder, Harli Grant, Austin Chou, Cutter A. Lindbergh, Joel H. Kramer, Bruce L. Miller, and Fanny M. Elahi
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2023
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31. Alzheimer's disease phenotypes show different sleep architecture
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Neus Falgàs, Christine M. Walsh, Leslie Yack, Alexander J. Simon, Isabel E. Allen, Joel H. Kramer, Howard J. Rosen, Renaud La Joie, Gil Rabinovici, Bruce Miller, Salvatore Spina, William W. Seeley, Kamalini Ranasinghe, Keith Vossel, Thomas C. Neylan, and Lea T. Grinberg
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2023
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32. Frontotemporal dementia
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Molly Memel, Joel H. Kramer, and Doris Chen
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- 2023
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33. Behavioural subphenotypes and their anatomic correlates in neurodegenerative disease
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Ashlin R K Roy, Samir Datta, Emily Hardy, Virginia E Sturm, Joel H Kramer, William W Seeley, Katherine P Rankin, Howard J Rosen, Bruce L Miller, and David C Perry
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Aging ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurodegenerative ,Alzheimer's disease ,frontotemporal dementia ,Brain Disorders ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Mental Health ,Rare Diseases ,Neurology ,Neurological ,Acquired Cognitive Impairment ,2.1 Biological and endogenous factors ,neurodegenerative diseases ,neuropsychiatric symptoms ,Dementia ,Aetiology ,Alzheimer’s disease ,Biological Psychiatry - Abstract
Patients with neurodegenerative disorders experience a range of neuropsychiatric symptoms. The neural correlates have been explored for many individual symptoms, such as apathy and disinhibition. Atrophy patterns have also been associated with broadly recognized syndromes that bring together multiple symptoms, such as the behavioural variant of frontotemporal dementia. There is substantial heterogeneity of symptoms, with partial overlap of behaviour and affected neuroanatomy across and within dementia subtypes. It is not well established if there are anatomically distinct behavioural subphenotypes in neurodegenerative disease. The objective of this study was to identify shared behavioural profiles in frontotemporal dementia-spectrum and Alzheimer’s disease-related syndromes. Additionally, we sought to determine the underlying neural correlates of these symptom clusters. Two hundred and eighty-one patients diagnosed with one of seven different dementia syndromes, in addition to healthy controls and individuals with mild cognitive impairment, completed a 109-item assessment capturing the severity of a range of clinical behaviours. A principal component analysis captured distinct clusters of related behaviours. Voxel-based morphometry analyses were used to identify regions of volume loss associated with each component. Seven components were identified and interpreted as capturing the following behaviours: Component 1—emotional bluntness, 2—emotional lability and disinhibition, 3—neuroticism, 4—rigidity and impatience, 5—indiscriminate consumption, 6—psychosis and 7—Geschwind syndrome-related behaviours. Correlations with structural brain volume revealed distinct neuroanatomical patterns associated with each component, including after controlling for diagnosis, suggesting that localized neurodegeneration can lead to the development of behavioural symptom clusters across various dementia syndromes.
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- 2023
34. State and trait characteristics of anterior insula time-varying functional connectivity.
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Lorenzo Pasquini, Gianina Toller, Adam Staffaroni, Jesse A. Brown, Jersey Deng, Alex J. Lee, Katarzyna Kurcyus, Suzanne M. Shdo, Isabel Allen, Virginia E. Sturm, Yann Cobigo, Valentina Borghesani, Giovanni Battistella, Maria Luisa Gorno-Tempini, Katherine P. Rankin, Joel H. Kramer, Howard H. Rosen, Bruce L. Miller, and William W. Seeley
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- 2020
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35. Left-handedness, learning disability, autoimmune disease, and seizure history influence age at onset and phenotypical targeting of Alzheimer’s disease
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Zachary A. Miller, Rik Ossenkoppele, Neill R. Graff-Radford, Isabel E. Allen, Wendy Shwe, Lynne Rosenberg, Dustin J Olguin, Michael G. Erkkinen, P. Monroe Butler, Salvatore Spina, Jennifer S. Yokoyama, Rahul S. Desikan, Philip Scheltens, Wiesje van der Flier, Yolande Pijnenburg, Emma Wolters, Rosa Rademakers, Daniel H. Geschwind, Joel H. Kramer, Howard J. Rosen, Katherine P. Rankin, Lea T. Grinberg, William W. Seeley, Virginia Sturm, David C. Perry, Bruce L. Miller, Gil D. Rabinovici, and Maria Luisa Gorno-Tempini
- Abstract
BackgroundRisk factors associated with sporadic non-amnestic and early-onset Alzheimer’s disease remain underexamined. We investigated a large, clinically heterogeneous Alzheimer’s disease cohort for frequencies of established Alzheimer’s disease risk factors (hypertension, hyperlipidemia, diabetes mellitus,APOE-ɛ4 frequency, and years of education), alongside a suite of novel factors with historical theoretical association (non-right-handedness, learning disability, seizures, and autoimmune disease).MethodsIn this case-control study, we screened the demographic and health histories of 750 consecutive early-onset and 750 late-onset Alzheimer’s disease patients from the University of California San Francisco Memory and Aging Center for the prevalence of conventional risk and novel Alzheimer’s disease factors and compared these results with 8,859 Alzheimer’s disease individuals from the National Alzheimer’s Coordinating Center, Amsterdam University Medical Center, Amsterdam, and Mayo Clinic, Jacksonville.ResultsEarly-onset Alzheimer’s disease was associated with significantly lower frequencies of established risk factors (hypertension, hyperlipidemia, diabetes mellitus, allpAPOE-ɛ4,p=0.03) and significantly higher frequencies of novel factors (non-right-handedness, learning disability, active seizure, allpp=0.002, and autoimmune disease,p=0.007). Logistic regressions predicting EOAD vs. LOAD controlling for sex, education,APOE-ɛ4 status, typical, and novel risk factors, produced findings consistent with the above. Principal component analysis loaded novel factors into two components, non-right-handedness and learning disability versus seizure and autoimmune disease, and the combination of factors from both components resulted in an exponential decrease in age at onset from any single factor alone.APOE-ɛ4 provided no additional contribution to age at onset decreases within the non-amnestic Alzheimer’s disease cohort but shifted the age of onset 3 years earlier within amnestic presentations (p=0.013).ConclusionsWe identified non-right-handedness, learning disability, seizures, and autoimmune disease as novel factors that affect both the age at onset and phenotypical targeting of Alzheimer’s disease. Together these results support a new theoretical framework of neurodegenerative disease susceptibility and that through the collection of detailed developmental and health history, neurodegenerative disease risk in some may be highly predictable, offering new opportunities towards early detection, monitoring, therapeutic intervention, and ultimately disease prevention.
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- 2022
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36. Sex and APOE‐ ε 4 carrier effects on early‐onset Alzheimer’s disease pathology
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Paige E. Logan, Sára Nemes, Leonardo Iaccarino, Nidhi S. Mundada, Renaud La Joie, Paul Aisen, Jeffrey L. Dage, Ani Eloyan, Anne M. Fagan, Tatiana M. Foroud, Constantine Gatsonis, Dustin B. Hammers, Clifford R. Jack, Joel H. Kramer, Robert Koeppe, Andrew J. Saykin, Arthur W. Toga, Prashanthi Vemuri, Alireza Atri, Gregory S. Day, Ranjan Duara, Neill R. Graff‐Radford, Lawrence S. Honig, David T. Jones, Joseph C. Masdeu, Mario F. Mendez, Chiadi U. Onyike, Emily J. Rogalski, Sharon Sha, Robert W. Turner, Kyle B. Womack, Maria C. Carrillo, Gil D. Rabinovici, Bradford C. Dickerson, and Liana G. Apostolova
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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37. Emergence of visual artistic creativity in frontotemporal dementia
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Adit, Friedberg, Lorenzo, Pasquini, Ryan T, Diggs, Erika Alma, Glaubitz, Lucia, Lopez, Jesse A, Brown, Katherine P, Rankin, Isabel Elaine, Allen, Renaud, La Joie, Leonardo, Iaccarino, Nidhi S, Mundada, Ignacio, Illán-Gala, Luke W, Bonham, Jennifer S, Yokoyama, Zachary A, Miller, Gil D, Rabinovici, Joel H, Kramer, Howard J, Rosen, Maria Luisa Gorno, Tempini, William W, Seeley, and Bruce L, Miller
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Abstract
Emergence of novel visual artistic skills has been described in neurodegenerative disorders, particularly in the frontotemporal dementia - amyotrophic lateral sclerosis (FTD-ALS) spectrum, but associated clinical and genetic features and the underlying neural mechanisms have not been systematically examined. We aimed to address these gaps.We performed comprehensive chart review of all 734 participants in the University of California San Francisco FTD Program Project Grant who had a clinical syndrome within the FTD-ALS spectrum. This review allowed us to ascertain subjects meeting current FTD-ALS clinical research criteria who had: (1) an emergence of novel visual artistic skills or (2) a change in the style of visual art produced or (3) a significant increase in quantity of visual art produced. Clinical data, imaging studies, and genetic information were collected and analyzed.Among the 734 patients screened, 45 were excluded due to lack of available research notes. We identified a change in visual artistic creativity in 17/689 patients (prevalence 2.5%). Mean age of FTD symptom onset was 57.4 (±10.4), and the visual artistic creativity (VAC) change was reported an average of 0.7 years (±10.1) prior to FTD symptom onset. Of the 17 patients with VAC, 8 exhibited no prior interest in art, 2 were professional visual artists who experienced a change in artistic style, and 7 reported some prior interest in art but a substantial change of style or quantity. Artistic output was diverse however bright colors and non-human subjects were prominent. VAC occurred in patients with semantic variant primary progressive aphasia (8), behavioral variant FTD (3), nonfluent variant primary progressive aphasia (2), progressive supranuclear palsy - Richardson's syndrome (2), corticobasal syndrome (1), and ALS (1). None carried a common pathogenic variant in a FTD gene.Change in VAC is an uncommon but early positive symptom that occurs in patients across the FTD-ALS clinical spectrum but appears most common in patients with anterior temporal lobe degeneration. We are pursuing the neural mechanisms of VAC through structural and functional neuroimaging studies.
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- 2022
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38. Physical Activity Relates to Lower Astrocytic Activation and Axonal Breakdown in Clinically Normal Older Adults
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Anna M VandeBunte, Shannon Y. Lee, Emily W Paolillo, Julio C. Rojas, Brandon Chan, Argentina Lario Lago, Joel H. Kramer, and Kaitlin B Casaletto
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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39. Peripheral inflammation and cognition in older adults with and without cognitive impairment
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Christina G. Wong, Chad L. Cross, Jefferson W Kinney, Aaron Ritter, Jessica ZK Caldwell, and Joel H. Kramer
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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40. Baseline Reliability and Six‐Month Stability of a Remotely Administered Battery of Smartphone Cognitive Tests
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Jack C Taylor, Annie L Clark, Hilary W. Heuer, Amy B Wise, Masood Manoochehri, Leah K. Forsberg, Carly T. Mester, Meghana Rao, Danielle Brushaber, Joel H. Kramer, Bradley F. Boeve, Howard J. Rosen, Adam L. Boxer, and Adam M. Staffaroni
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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41. Sex modifies the association between hippocampal blood flow and episodic memory in cognitively unimpaired individuals
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Anna Brugulat‐Serrat, Yann Cobigo, Corrina S. Fonseca, Torie Tsuei, Lauren Goldberger, Howard J. Rosen, Joel H. Kramer, Fanny M Elahi, Adam M. Staffaroni, and Kaitlin B Casaletto
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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42. Construct Validity of the ALLFTD Mobile App Cognitive Tests: Associations with Gold Standard Clinical Measures and Brain Volume
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Adam M. Staffaroni, Annie L Clark, Jack C Taylor, Hilary W. Heuer, Amy B Wise, Masood Manoochehri, Leah K. Forsberg, Carly T. Mester, Meghana Rao, Danielle Brushaber, Julio C. Rojas, Joel H. Kramer, Bradley F. Boeve, Howard J. Rosen, Adam L. Boxer, and ALLFTD Consortium
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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43. Validation and utility of plasma neurofilament light as a biomarker for vascular cognitive impairment
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Tiffany F Kautz, Julia J Mathews, Danielle Parent, Tiffany L Sudduth, Qianqian Liu, Crystal Wiedner, Chen‐Pin Wang, Djass Mbangdadji, Joshua C Bis, Abhay P Sagare, Alexa S Beiser, George Pottanat, Hugo J Aparicio, Jeffery F Thompson, Kelsey Erickson, Lee‐Way Jin, Mitzi M Gonzales, Saptaparni Ghosh, Charles S. DeCarli, Danny JJ Wang, Donna M Wilcock, Gary A Rosenberg, Hanzhang Lu, Joel H. Kramer, Lenore J. Launer, Myriam Fornage, Thomas H Mosley, Pauline Maillard, Vilmundur Gudnason, Herpreet Singh, Karl G Helmer, Kristin Schwab, Steven M Greenberg, Russell P. Tracy, Pia Kivisäkk, Sudha Seshadri, and Claudia L Satizabal
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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44. Spectral signatures associated with cognitive aging, APOE4, amyloid‐β and measures of axonal integrity in cognitively unimpaired adults
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Kamalini G Ranasinghe, Kaitlin B Casaletto, Kiwamu Kudo, Hannah M Lerner, Danielle Mizuiri, Renaud La Joie, Bruce L. Miller, Keith Vossel, Joel H. Kramer, William J. Jagust, Katherine P Rankin, Gil D. Rabinovici, and Srikantan S Nagarajan
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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45. APOE Genotype Moderates the Relationship Between Plasma Phosphorylated‐tau181 and Pattern Separation Performance in Non‐demented Adults
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Valentina E Diaz, Molly B Memel, Leslie S Gaynor, Eva Q. Gontrum, Brandon Chan, Argentina Lario Lago, Michael A. Yassa, Julio C. Rojas, Kaitlin B Casaletto, Joel H. Kramer, and Rowan Saloner
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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46. Alzheimer’s Disease Proteinopathy and Synaptic Integrity: The Protective Role of Physical Activity
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Shannon Y. Lee, Emily W Paolillo, Anna M. VandeBunte, Ann Brinkmalm, Kaj Blennow, Henrik Zetterberg, Joel H. Kramer, and Kaitlin B Casaletto
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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47. Plasma phosphorylated‐tau181 is an indicator of early manifestations of neuropsychiatric symptoms in younger subclinical individuals
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Eva Q. Gontrum, Rowan Saloner, Brandon Chan, Argentina Lario Lago, Julio C. Rojas, Kaitlin B Casaletto, and Joel H. Kramer
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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48. Latent profiles of physical actigraphy patterns among older adults: Differential relationships with cognition and vascular burden by sex
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Emily W Paolillo, Shannon Y. Lee, Nina Djukic, Anna M. VandeBunte, Rowan Saloner, Joel H. Kramer, and Kaitlin B Casaletto
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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49. Plasma glial fibrillary acidic protein as a moderator along the Alzheimer’s disease biomarker cascade
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Rowan Saloner, Breton M. Asken, Eva Q. Gontrum, Brandon Chan, Argentina Lario Lago, Julio C. Rojas, Bruce L. Miller, Gil D. Rabinovici, Kaitlin B Casaletto, and Joel H. Kramer
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
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50. Blood‐brain barrier dysfunction is associated with A/T/N biomarkers and cognition in the aging brain
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Yasmine Tabdili, Krystal Courtney D Belmonte, Nivetha Brathaban, Emma Iorio, Ryan Park, Anna M VandeBunte, Kaitlin B Casaletto, Joel H. Kramer, Katerina Akassoglou, and Fanny M Elahi
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
- Full Text
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