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Acquired synesthesias have been reported in association with deafferentation of the visual system, temporal lobe seizures, and the use of psychedelics. Based on our review of the literature, the appearance of synesthesias after a thalamic stroke has been reported only once. We present the case of a 45-year-old hypertensive male who, 9 months after a hemorrhagic stroke involving the left lateral posterior nucleus of the thalamus developed persistent sound-tactile, sound-color, and grapheme-gustatory synesthesias. Moreover, the patient noted that even thinking about a sensory stimulus could trigger the experience of another sensory modality, a conceptual type of synesthesia. [ABSTRACT FROM AUTHOR]

Objectives: The primary objective of this study was to describe a model for specialized psychogeriatric consultation to long-term care homes in a large metropolitan Canadian city and to provide an overview of the diagnostic and demographic data of patients referred for assessment.Methods: Forty long-term care homes and 13 geriatric mental health outreach teams were surveyed and provided feedback on the model. A retrospective chart review (N=88) was also conducted to confirm the survey results and to provide an overview of the types of patients being seen.Results: Team data indicated that 96% of the homes they served (N=81) were using their services, that all referrals were appropriate, and that their recommendations were implemented in over 50% of cases. Referred patients tended to be older (41% age 85 or older); were referred mainly for agitation, aggression, or depressed mood (over 90%); and mainly had a mood or cognitive disorder (over 90%).Conclusions: These preliminary data suggest that the implementation of specialized psychogeriatric consultation to long-term care may be beneficial, but future studies are required to clarify its usefulness. [ABSTRACT FROM AUTHOR]

BACKGROUND: In spite of the prevalence of delusions in Alzheimer's disease (AD) and their association with poor outcomes, there has been little study of the impact of delusions on real-world functioning. METHOD: A number of databases, including Psychlit and Medline, were searched using the keywords: delusions, functional outcomes, activities of daily living, dementia, and Alzheimer's disease. Studies were included in the review if they were in English, restricted to patients with AD, and addressed delusions and function. RESULTS: The review yielded a total of 6 studies, 3 of which showed a correlation between delusions and real-world functioning and 3 of which did not. CONCLUSION: A critical analysis of the existing studies suggests that there may be an association between delusions and impaired real-world functioning. We believe that 2 of the 3 negative studies did not show an association due to issues relating to study design and the use of measures insensitive to executive impairment. This review highlights the future need for more scientifically rigorous studies to clarify this association, so as to ultimately improve treatment outcomes for patients. [ABSTRACT FROM AUTHOR]

Importance: Older adults with major depressive disorder (MDD) or mild cognitive impairment (MCI) are at high risk for cognitive decline., Objective: To assess the efficacy of cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) targeting the prefrontal cortex in slowing cognitive decline, acutely improving cognition, and reducing progression to MCI or dementia in older adults with remitted MDD (rMDD), MCI, or both., Design, Setting, and Participants: This randomized clinical trial was conducted at 5 academic hospitals in Toronto, Ontario, Canada. Participants were older adults who had rMDD (with or without MCI, age ≥65 y) or MCI without rMDD (age ≥60 y). Assessments were made at baseline, month 2, and yearly from baseline for 3 to 7 years., Interventions: CR plus tDCS (hereafter, active) or sham plus sham 5 days a week for 8 weeks followed by twice-a-year 5-day boosters and daily at-home CR or sham CR., Main Outcomes and Measures: The primary outcome was change in global composite cognitive score. Secondary outcomes included changes in 6 cognitive domains, moderating effect of the diagnosis, moderating effect of APOE ε4 status, change in composite score at month 2, and progression to MCI or dementia over time., Results: Of 486 older adults who provided consent, 375 (with rMDD, MCI, or both) received at least 1 intervention session (mean [SD] age, 72.2 [6.4] years; 232 women [62%] and 143 men [38%]). Over a median follow-up of 48.3 months (range, 2.1-85.9), CR and tDCS slowed cognitive decline in older adults with rMDD or MCI (adjusted z score difference [active - sham] at month 60, 0.21; 95% CI, 0.07 to 0.35; likelihood ratio test [LRT] P = .006). In the preplanned primary analysis, CR and tDCS did not improve cognition acutely (adjusted z score difference [active - sham] at month 2, 0.06, 95% CI, -0.006 to 0.12). Similarly, the effect of CR and tDCS on delaying progression from normal cognition to MCI or MCI to dementia was weak and not significant (hazard ratio, 0.66; 95% CI, 0.40 to 1.08; P = .10). Preplanned analyses showed treatment effects for executive function (LRT P = .04) and verbal memory (LRT P = .02) and interactions with diagnosis (P = .01) and APOE ε4 (P < .001) demonstrating a larger effect among those with rMDD and in noncarriers of APOE ε4., Conclusions and Relevance: The study showed that CR and tDCS, both targeting the prefrontal cortex, is efficacious in slowing cognitive decline in older adults at risk of cognitive decline, particularly those with rMDD (with or without MCI) and in those at low genetic risk for Alzheimer disease., Trial Registration: ClinicalTrials.gov Identifier: NCT02386670.

Introduction: Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized., Methods: Participants clinically diagnosed with Alzheimer's disease or mild cognitive impairment (AD/MCI), frontotemporal dementia, Parkinson's disease, or cerebrovascular disease were stratified by the presence of the APOE ε4 allele. Volumetric magnetic resonance imaging, plasma amyloid/tau/neurodegeneration biomarkers, and cognitive performance were quantified., Results: Across all diagnostic groups, Hcy was associated with lower brain parenchymal fraction and greater neurofilament light chain in APOE ε4 non-carriers only. In AD/MCI, Hcy was associated with phosphorylated tau 217 in APOE ε4 non-carriers, but not in carriers. Exploratory analyses revealed interactions between Hcy and APOE ε4 on memory and visuospatial function., Discussion: Hcy may contribute to neurodegeneration depending on the presence of the APOE ε4 allele and specific disease processes. Trials on vitamin B12 supplementation may consider stratifying by APOE genotype. Highlights Homocysteine (Hcy) was associated with neurodegenerative biomarkers across disease groups. Relationships with Hcy were predominantly found in apolipoprotein E (APOE) ε4 non-carriers. In Alzheimer's disease, associations between Hcy and phosphorylated tau 217 were found in APOE ε4 non-carriers only. Significant interactions existed between Hcy and APOE ε4 status on cognition., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Inner dialogue and inner speech are normal systems of cerebral intrapersonal communication, crucial to self-awareness. Lesions affecting the cerebral network involved in these systems have been associated with the occurrence of Auditory Verbal Hallucinations (AVHs). These are regarde as a continuum phenomenon experienced by healthy, individuals, as well as those with psychiatric disorders. In this paper, two patients with left hemispheric lesions of different pathologies, vascular and tumor, respectively, who during their recovery of motor and sensory functions presented severe deregulation in their inner dialogue. In both cases, the damaged left dominant hemisphere adopted arrogant, demeaning, and abusive inner speech, while the right non-dominant side, which commands the rehabilitation of the lost functions, was subdued and quiet. This abusive unilateral inner dialogue was present until adequate recovery of independent functions was achieved for both patients.

Sex differences in patterns of cortical thickness and neuropsychiatric symptom (NPS) burden were examined among individuals with Alzheimer's disease (AD) and two copies (homozygote carriers) of the e4 allele of the apolipoprotein gene (APOE). A total of 752 participants with a clinical etiologic diagnosis of AD were selected from the National Alzheimer's Coordinating Center (NACC) database. Bayesian multilevel regression was used to examine both the within- and between-sex differences in gray-matter cortical thickness and total NPS burden associated with APOE homozygosity. Female homozygote carriers displayed a high probability of having reduced cortical thickness primarily in medial-lateral temporal regions and a greater burden of NPS, relative to both non-homozygous females and homozygous males. These findings support the notion that APOE4 status affects cortical thickness and symptom burden in men and women with AD differentially, with females showing more pronounced effects in brain areas known to be vulnerable in early AD. Future investigations should attempt to elucidate the proposed pattern of decline longitudinally., (© 2024 The Author(s). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

N-acetyl-aspartate (NAA) and myo-inositol (mI) are neurometabolites reflecting neuronal viability and astrocyte activity, respectively. These are quantified using proton magnetic resonance spectroscopy (1H-MRS) and may be biomarkers for Alzheimer's disease dementia (AD). Our objectives were: 1) Compare dorsolateral prefrontal cortex (DLPFC) NAA and mI levels between AD and cognitively healthy control participants (HC) 2) assess if NAA/mI ratio can distinguish groups, and 3) explore the relationship between metabolites and cognition. The study included 64 participants over 55, 41 with AD. Bilateral DLPFC NAA and mI levels were quantified using 3 T 1H-MRS and normalized to H2O. NAA and NAA/mI ratio were lower in AD vs. HC. mI was unchanged. The NAA/mI ratio at a cut-off value of 1.69 showed 59% sensitivity and 87% specificity at distinguishing AD from HC. NAA was associated positively with cognition. In conclusion, DLPFC metabolite changes suggest altered mitochondrial function in AD. NAA/mI ratio shows good specificity in distinguishing AD from HC, suggesting its role in complementing other biomarkers. Future studies should evaluate NAA/mI ratio with other disease specific biomarkers., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The risk of violence is higher in schizophrenia spectrum disorders (SSD) compared to the general population and it is a pressing and understudied issue. Several dispositional and environmental factors have been previously correlated with violence, however, there has been little success in assessing their ability to predict violence patterns across the life span. This study aims to assess violence prediction based on personality traits, psychological resilience, and life-course adversities in a non-forensic population of SSD patients. In a sample of 231 patients with SSD, we assessed violence using the Brown-Goodwin History of Lifetime Aggression Scale and conducted cross-sectional assessments of possible predictors such as childhood trauma, personality traits and resilience scores. We then utilized a logistic regression classification algorithm to predict different violence trajectories based on the proposed risk factors. Our model significantly predicted individuals with violence in both childhood and adulthood, as well as childhood-only violence (p < 0.001). However, the model did not show significance for adult-only violence (p = 0.604). In all given trajectories, female sex appeared to be protective against violence, while stressful life events appeared to contribute to it. These results suggest that distinct factors can better inform risk assessment of lifespan violence patterns for personalized interventions in SSD., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases., Methods: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative., Results: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH., Discussion: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia., Highlights: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Long-term potentiation (LTP)-like activity can be induced by stimulation protocols such as paired associative stimulation (PAS). We aimed to determine whether PAS-induced LTP-like activity (PAS-LTP) of the dorsolateral prefrontal cortex (DLPFC) is associated with cortical thickness and other structural measures impaired in Alzheimer's dementia (AD). We also explored longitudinal relationships between these brain structures and PAS-LTP response after a repetitive PAS (rPAS) intervention. Mediation and regression analyses were conducted using data from randomized controlled trials with AD and healthy control participants. PAS-electroencephalography assessed DLPFC PAS-LTP. DLPFC thickness and surface area were acquired from T1-weighted magnetic resonance imaging. Fractional anisotropy and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF)-a tract important to induce PAS-LTP-were measured with diffusion-weighted imaging. AD participants exhibited reduced DLPFC thickness and increased SLF MD. There was also some evidence that reduction in DLPFC thickness mediates DLPFC PAS-LTP impairment. Longitudinal analyses showed preliminary evidence that SLF MD, and to a lesser extent DLPFC thickness, is associated with DLPFC PAS-LTP response to active rPAS. This study expands our understanding of the relationships between brain structural changes and neuroplasticity. It provides promising evidence for a structural predictor to improving neuroplasticity in AD with neurostimulation. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Objectives: To investigate whether a history of traumatic brain injury (TBI) is associated with greater long-term grey-matter loss in patients with mild cognitive impairment (MCI)., Methods: 85 patients with MCI were identified, including 26 with a previous history of traumatic brain injury (MCI[TBI-]) and 59 without (MCI[TBI+]). Cortical thickness was evaluated by segmenting T1-weighted MRI scans acquired longitudinally over a 2-year period. Bayesian multilevel modelling was used to evaluate group differences in baseline cortical thickness and longitudinal change, as well as group differences in neuropsychological measures of executive function., Results: At baseline, the MCI[TBI+] group had less grey matter within right entorhinal, left medial orbitofrontal and inferior temporal cortex areas bilaterally. Longitudinally, the MCI[TBI+] group also exhibited greater longitudinal declines in left rostral middle frontal, the left caudal middle frontal and left lateral orbitofrontal areas sover the span of 2 years (median = 1-2%, 90%HDI [-0.01%: -0.001%], probability of direction (PD) = 90-99%). The MCI[TBI+] group also displayed greater longitudinal declines in Trail-Making-Test (TMT)-derived ratio (median: 0.737%, 90%HDI: [0.229%: 1.31%], PD = 98.8%) and differences scores (median: 20.6%, 90%HDI: [-5.17%: 43.2%], PD = 91.7%)., Conclusions: Our findings support the notion that patients with MCI and a history of TBI are at risk of accelerated neurodegeneration, displaying greatest evidence for cortical atrophy within the left middle frontal and lateral orbitofrontal frontal cortex. Importantly, these results suggest that long-term TBI-mediated atrophy is more pronounced in areas vulnerable to TBI-related mechanical injury, highlighting their potential relevance for diagnostic forms of intervention in TBI., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures., Design: Secondary cross-sectional analysis using latent profile analysis., Setting: Multisite clinical trial in Toronto, Canada., Participants: One hundred seventy-eight participants who met DSM-5 criteria for rMDD without MCI (rMDD-MCI; n = 60) or with MCI (rMDD + MCI; n = 118)., Measurements: Demographic, clinical, neuroimaging measures, and domain scores from a neuropsychological battery assessing verbal memory, visuospatial memory, processing speed, working memory, language, and executive function., Results: We identified three latent profiles: Profile 1 (poor cognition; n = 75, 42.1%), Profile 2 (intermediate cognition; n = 75, 42.1%), and Profile 3 (normal cognition; n = 28, 15.7%). Compared to participants with Profile 3, those with Profile 1 or 2 were older, had lower education, experienced a greater burden of medical comorbidities, and were more likely to have MCI. The profiles did not differ on the severity of residual symptoms, age of onset of rMDD, number of depressive episodes, psychotropic medication, cerebrovascular risk, ApoE4 carrier status, or family history of depression, dementia, or Alzheimer's disease. The profiles differed in cortical thickness of 15 regions, with the most prominent effects for left precentral and pars opercularis, and right inferior parietal and supramarginal., Conclusion: Older patients with rMDD can be grouped cross-sectionally based on data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. Future research should determine the differential risk for dementia of these data-driven subgroups., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The common requirement to set the time to "10 past 11" on the Clock Drawing Test is intended to elicit a stimulus bound response (SBR), in which the responder is "pulled" to the salient stimulus "10," resulting in hands set at "10 before 11." SBRs are considered markers of executive dysfunction, although this assumption has not yet been validated. We compared SBR and other time-setting errors on inhibitory control tests, hypothesizing that they represent related constructs. The role of semantic dysfunction in the formation of those errors was also investigated. We examined baseline test performance of participants with Mild Cognitive Impairment or a history of depression, and control participants, enrolled in a dementia prevention study. Among 258 participants, we identified clocks with SBRs ( n  = 16), other time errors ( n  = 22), or no errors at all ( n  = 42). Performance between the groups with SBRs and other time-setting errors did not differ on any of the executive tests, and both error groups performed significantly worse than the No Error group on the semantic tests. Control for covariates further supported semantic and executive components in time-setting errors. Both semantic and inhibitory control deficits may underlie time representation errors in general.

Theta-gamma coupling (TGC) is a neurophysiological process that supports working memory. Working memory is associated with other clinical and biological features. The extent to which TGC is associated with these other features and whether it contributes to working memory beyond these features is unknown. Two-hundred-and-three older participants at risk for Alzheimer's dementia-98 with mild cognitive impairment (MCI), 39 with major depressive disorder (MDD) in remission, and 66 with MCI and MDD (MCI + MDD)-completed a clinical assessment, N-back-EEG, and brain MRI. Among them, 190 completed genetic testing, and 121 completed [ 11 C] Pittsburgh Compound B ([11C] PIB) PET imaging. Hierarchical linear regressions were used to assess whether TGC is associated with demographic and clinical variables; Alzheimer's disease-related features ( APOE ε4 carrier status and β-amyloid load); and structural features related to working memory. Then, linear regressions were used to assess whether TGC is associated with 2-back performance after accounting for these features. Other than age, TGC was not associated with any non-neurophysiological features. In contrast, TGC (β = 0.27; p  = 0.006), age (β = - 0.29; p  = 0.012), and parietal cortical thickness (β = 0.24; p  = 0.020) were associated with 2-back performance. We also examined two other EEG features that are linked to working memory-theta event-related synchronization and alpha event-related desynchronization-and found them not to be associated with any feature or performance after accounting for TGC. Our findings suggest that TGC is a process that is independent of other clinical, genetic, neurochemical, and structural variables, and supports working memory in older adults at risk for dementia., Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09938-y., Competing Interests: Conflict of interestRP, HB, AG, NH, MM, NRR, WW and RZ report no biomedical financial interests or potential conflicts of interest. DMB receives research support from the CIHR, NIH, Brain Canada and the Temerty Family Foundation through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd, and he was the principal site investigator for three sponsor-initiated studies for Brainsway Ltd. He receives in-kind equipment support from Magventure for investigator-initiated research. He received medication supplies for an investigator-initiated trial from Indivior. He has participated in a scientific advisory board meeting for Janssen and Welcony Inc. CEF receives grant funding from Brain Canada, Patient Centred Outcomes Research Institute (PCORI), St. Michaels Hospital Foundation, Hoffman LaRoche and Vielight Inc. AJF has received grant support from the U.S. National Institutes of Health, the Patient Centered Outcomes Research Institute, the Canadian Institutes of Health Research, Brain Canada, the Ontario Brain Institute, the Alzheimer's Association, AGE-WELL, and the Canadian Foundation for Healthcare Improvement. AGG has obtained academic grants during the last 5 years from Canadian Institute of Health Research, Centre for Aging and Brain Health Innovation, Brain Canada Foundation, Brain & Behavior Research Foundation, Ontario Ministry of Economic Development and Innovation, Ontario Mental Health Foundation, Ontario Ministry of Health and Long Term Care Alternate Funding Plan, American Foundation for Suicide Prevention, Catalyst Fund: Miner's Lamp Innovation Fund in Prevention and Early Detection of Severe Mental Illness, Northern Ontario Academic Medicine Association, Society for Nuclear Medicine and Molecular Imaging, Researcher-Clinician Partnership Program (RCP2), Spark, W. Garfield Weston Foundation, Labatt Family Network for Research on the Biology of Depression, and PSI Foundation. JLK is a member of the Scientific Advisory Board (unpaid) of Myriad Genetics, and is author on patents relating to pharmacogenetics of psychiatric disorders. SK has received grant support from Brain Canada, NIH, Brain and Behavior Foundation (NARSAD), BrightFocus Foundation, Weston Brain Institute, Canadian Centre for Aging and Brain Health Innovation, CAMH foundation and University of Toronto, and in Kind equipment support from Soterix Medical Inc. KLL has grant support from the U.S. National Institutes of Health, the Canadian Institutes of Health Research, the Weston Brain Institute, the Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association, has received consultation fees from Acadia, BioXcel Therapeutics, Cerevel Therapeutics, ICG Pharma, Kondor Pharma, Otsuka, and holds stock options in Highmark Interactive. LM reports no biomedical financial interests or potential conflicts of interest. BHM holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). Within the past 5 years, he has also received research support from Eli Lilly (medications for a NIH-funded clinical trial) and Pfizer (medications for a NIH-funded clinical trial). BGP is holder of United States Provisional Patent No. 16/490,680, Canadian Provisional Patent No. 3,054,093 and of United States Provisional Patent No.17/396,030 for a cell-based assay and kits for assessing serum anticholinergic activity. AV receives funding from the National Institute of Mental Health, Canadian Institutes of Health Research, Canada Foundation for Innovation, CAMH Foundation, and the University of Toronto. TKR has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute. TKR also received in-kind equipment support for an investigator-initiated study from Magstim, and in-kind research accounts from Scientific Brain Training Pro. TKR participated in 2021 in an advisory board for Biogen Canada Inc. TKR is also holder of the United States Provisional Patent No. 17/396,030 that describes cell-based assays and kits for assessing serum cholinergic receptor activity., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Driving is the preferred mode of transportation for adults across the healthy age span. However, motor vehicle crashes are among the leading causes of injury and death, especially for older adults, and under distracted driving conditions. Understanding the neuroanatomical basis of driving may inform interventions that minimize crashes. This exploratory study examined the neuroanatomical correlates of undistracted and distracted simulated straight driving., Methods: One-hundred-and-thirty-eight participants (40.6% female) aged 17-85 years old (mean and SD = 58.1 ± 19.9 years) performed a simulated driving task involving straight driving and turns at intersections in a city environment using a steering wheel and foot pedals. During some straight driving segments, participants responded to auditory questions to simulate distracted driving. Anatomical T1-weighted MRI was used to quantify grey matter volume and cortical thickness for five brain regions: the middle frontal gyrus (MFG), precentral gyrus (PG), superior temporal cortex (STC), posterior parietal cortex (PPC), and cerebellum. Partial correlations controlling for age and sex were used to explore relationships between neuroanatomical measures and straight driving behavior, including speed, acceleration, lane position, heading angle, and time speeding or off-center. Effects of interest were noted at an unadjusted p -value threshold of 0.05., Results: Distracted driving was associated with changes in most measures of straight driving performance. Greater volume and cortical thickness in the PPC and cerebellum were associated with reduced variability in lane position and heading angle during distracted straight driving. Cortical thickness of the MFG, PG, PPC, and STC were associated with speed and acceleration, often in an age-dependent manner., Conclusion: Posterior regions were correlated with lane maintenance whereas anterior and posterior regions were correlated with speed and acceleration, especially during distracted driving. The regions involved and their role in straight driving may change with age, particularly during distracted driving as observed in older adults. Further studies should investigate the relationship between distracted driving and the aging brain to inform driving interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guan, Churchill, Fischer, Graham and Schweizer.)

Background: The International Psychogeriatric Association (IPA) published a provisional consensus definition of agitation in cognitive disorders in 2015. As proposed by the original work group, we summarize the use and validation of criteria in order to remove "provisional" from the definition., Methods: This report summarizes information from the academic literature, research resources, clinical guidelines, expert surveys, and patient and family advocates on the experience of use of the IPA definition. The information was reviewed by a working group of topic experts to create a finalized definition., Results: We present a final definition which closely resembles the provisional definition with modifications to address special circumstances. We also summarize the development of tools for diagnosis and assessment of agitation and propose strategies for dissemination and integration into precision diagnosis and agitation interventions., Conclusion: The IPA definition of agitation captures a common and important entity that is recognized by many stakeholders. Dissemination of the definition will permit broader detection and can advance research and best practices for care of patients with agitation.

Objectives: To develop an agitation reduction and prevention algorithm is intended to guide implementation of the definition of agitation developed by the International Psychogeriatric Association (IPA)., Design: Review of literature on treatment guidelines and recommended algorithms; algorithm development through reiterative integration of research information and expert opinion., Setting: IPA Agitation Workgroup., Participants: IPA panel of international experts on agitation., Intervention: Integration of available information into a comprehensive algorithm., Measurements: None., Results: The IPA Agitation Work Group recommends the Investigate, Plan, and Act (IPA) approach to agitation reduction and prevention. A thorough investigation of the behavior is followed by planning and acting with an emphasis on shared decision-making; the success of the plan is evaluated and adjusted as needed. The process is repeated until agitation is reduced to an acceptable level and prevention of recurrence is optimized. Psychosocial interventions are part of every plan and are continued throughout the process. Pharmacologic interventions are organized into panels of choices for nocturnal/circadian agitation; mild-moderate agitation or agitation with prominent mood features; moderate-severe agitation; and severe agitation with threatened harm to the patient or others. Therapeutic alternatives are presented for each panel. The occurrence of agitation in a variety of venues-home, nursing home, emergency department, hospice-and adjustments to the therapeutic approach are presented., Conclusions: The IPA definition of agitation is operationalized into an agitation management algorithm that emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches to reflect the clinical situation, and shared decision-making.

Whether individuals with mild cognitive impairment (MCI) and a history of major depressive disorder (MDD) are at a higher risk for cognitive decline than those with MCI alone is still not clear. Previous work suggests that a reduction in prefrontal cortical theta phase-gamma amplitude coupling (TGC) is an early marker of cognitive impairment. This study aimed to determine whether using a TGC cutoff is better at separating individuals with MCI or MCI with remitted MDD (MCI+rMDD) on cognitive performance than their clinical diagnosis. Our hypothesis was that global cognition would differ more between TGC-based groups than diagnostic groups. We analyzed data from 128 MCI (mean age: 71.8, SD: 7.3) and 85 MCI+rMDD (mean age: 70.9, SD: 4.7) participants. Participants completed a comprehensive neuropsychological battery; TGC was measured during the N-back task. An optimal TGC cutoff was determined during the performance of the 2-back. This TGC cutoff was used to classify participants into low vs. high-TGC groups. We then compared Cohen's d of the difference in global cognition between the high and low TGC groups to Cohen's d between the MCI and MCI+rMDD groups. We used bootstrapping to determine 95% confidence intervals for Cohen's d values using the whole sample. As hypothesized, Cohen's d for the difference in global cognition between the TGC groups was larger (0.64 [0.32, 0.88]) than between the diagnostic groups (0.10 [0.004, 0.37]) with a difference between these two Cohen's d's of 0.54 [0.10, 0.80]. Our findings suggest that TGC is a useful marker to identify individuals at high risk for cognitive decline, beyond clinical diagnosis. This could be due to TGC being a sensitive marker of prefrontal cortical dysfunction that would lead to an accelerated cognitive decline., (© 2024. The Author(s).)

Introduction: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases., Methods: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ) 42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD)., Results: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ 42/40 ., Discussion: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses., Methods: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits., Results: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively., Conclusions: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences., (© 2024 John Wiley & Sons Ltd.)

Background: There has been little direct examination of how traumatic brain injury (TBI) affects the rate of neurodegeneration for individuals with Alzheimer's disease (AD)., Methods: The study examined 89 cognitively normal adults (65 with and 24 without prior TBI) and 65 with AD (16 with and 49 without prior TBI). Cortical thickness was quantified from T1-weighted MRI scans at baseline and follow-up (mean interval 33.4 months). Partial least squares analysis was used to evaluate the effects of AD and TBI history on the longitudinal change in cortical thickness., Results: Significant group effects were identified throughout the frontal and temporal cortices. Comparison of the AD groups to their control cohorts showed greater relative atrophy for the AD cohort with prior TBI., Conclusion: These results indicate that a history of TBI exacerbates longitudinal declines in cortical thickness among AD patients, providing new insights into the shared pathomechanisms between these neurological conditions., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest.

Introduction: Traumatic brain injury (TBI) is associated with an accelerated course of dementia, although biological relationships are incompletely understood., Methods: The study examined 1124 participants, including 343 with Alzheimer disease (AD), 127 with AD with TBI, 266 cognitively normal adults with TBI, and 388 cognitively normal adults without TBI. Cortical thickness was quantified from T1-weighted magnetic resonance imaging data. Multiple linear regression was used to determine the interaction between AD and TBI on cortical thickness., Results: Among those with AD, TBI was associated with an earlier age of AD onset but, counterintuitively, less cortical thinning in frontotemporal regions relative to non-AD controls., Discussion: AD with TBI represents a distinct group from AD, likely with distinct pathologic contributions beyond gray matter loss. This finding has important implications for the diagnosis and treatment of AD in the presence of TBI and indicates that models of AD, aging, and neural loss should account for TBI history., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Almost half of older patients with major depressive disorder (MDD) present with cognitive impairment, and one-third meet diagnostic criteria for mild cognitive impairment (MCI). However, mechanisms linking MDD and MCI remain unclear. We investigated multivariate associations between brain structural alterations and cognition in 3 groups of older patients at risk for dementia, remitted MDD (rMDD), MCI, and rMDD+MCI, as well as cognitively healthy nondepressed control participants., Methods: We analyzed magnetic resonance imaging data and cognitive domain scores in participants from the PACt-MD (Prevention of Alzheimer's Disease With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression) study. Following quality control, we measured cortical thickness and subcortical volumes of selected regions from 283 T1-weighted scans and fractional anisotropy of white matter tracts from 226 diffusion-weighted scans. We assessed brain-cognition associations using partial least squares regressions in the whole sample and in each subgroup., Results: In the entire sample, atrophy in the medial temporal lobe and subregions of the motor and prefrontal cortex was associated with deficits in verbal and visuospatial memory, language skills, and, to a lesser extent, processing speed (p < .0001; multivariate r = 0.30, 0.34, 0.26, and 0.18, respectively). Widespread reduced white matter integrity was associated with deficits in executive functioning, working memory, and processing speed (p = .008; multivariate r = 0.21, 0.26, 0.35, respectively). Overall, associations remained significant in the MCI and rMDD+MCI groups, but not the rMDD or healthy control groups., Conclusions: We confirm findings of brain-cognition associations previously reported in MCI and extend them to rMDD+MCI, but similar associations in rMDD are not supported. Early-onset and treated MDD might not contribute to structural alterations associated with cognitive impairment., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status., Methods: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1)., Results: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood., Discussion: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: Inflammatory activation and increased immune response to lipopolysaccharide occur in both depression and cognitive decline and may link these two conditions. We investigated whether lipopolysaccharide (LPS), LPS binding protein (LBP) and peripheral biomarkers of immune response were associated with increased cerebral deposition of amyloid-beta (Abeta) in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD)., Design: Cross-sectional analysis., Setting: Five academic health centers in Toronto., Participants: Older adults with MCI with/without rMDD., Measurements: We investigated the associations among serum LPS, LBP, biomarkers of inflammatory activation - Interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and cerebral Abeta deposition quantified by positron emission tomography., Results: Among 133 study participants (82 with MCI and 51 with MCI+rMDD) there was no association between LPS (beta - 0.17, p = 0.8) or LBP (beta - 0.11, p = 0.12) and global deposition of Abeta following adjustment for age, gender, and APOE genotype in multivariable regression analyses. LBP was positively correlated with CRP (r = 0.5, p <0.001) and IL-6 (r = 0.2, p = 0.02) but no inflammatory biomarker was associated with Abeta deposition; rMDD was not associated with deposition of Abeta (beta -0.09, p = 0.22)., Conclusion: In this cross-sectional analysis, we did not find an association among LPS/LBP, immune biomarkers or rMDD and global deposition of Abeta. Future analyses should assess the longitudinal relationships between peripheral and central biomarkers of immune activation, depression and cerebral Abeta deposition., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Debate continues regarding the use of self- versus informant-report to diagnose mild cognitive impairment (MCI) with studies reporting patients both overestimating and underestimating their abilities relative to informants. We assessed concordance of self- versus informant-report of cognitive decline with objective cognitive and functional performance in the participants of the preventing Alzheimer's dementia with cognitive remediation plus transcranial direct current stimulation in mild cognitive impairment and depression randomized controlled trial (PACt-MD)., Method: Three hundred six participants with MCI, and their informants, reported on cognitive decline; the participants also completed a comprehensive assessment of objective cognitive and functional performance. Based on the discrepancy between self- versus informant-report of cognitive decline, we grouped participants into categories of underestimators, congruent estimators, and overestimators., Results: Informant- but not self-reported cognitive decline significantly correlated with objective cognitive performance. There were 68 underestimators, 94 congruent estimators, and 144 overestimators. Underestimators had significantly lower objective cognitive performance and functional performance than congruent estimators and overestimators. Cognitive performance significantly predicted functional performance in all three groups, and the relationship between cognitive and functional performance was moderated by the discrepancy between self- and informant-report., Conclusions: We showed a poor concordance among self-report of cognitive decline and both informant-report of cognitive decline and cognitive performance in patients with MCI. Our findings highlight clinical and research value in the assessment and consideration of degree of discrepancy between self- and informant-reports of cognitive decline in MCI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Major depressive disorder (MDD) in late life is a risk factor for mild cognitive impairment (MCI) and Alzheimer's disease. However, studies of gray matter changes have produced varied estimates of which structures are implicated in MDD and dementia. Changes in gray matter volume and cortical thickness are macrostructural measures for the microstructural processes of free water accumulation and dendritic spine loss., Methods: We conducted multishell diffusion imaging to assess gray matter microstructure in 244 older adults with remitted MDD ( n  = 44), MCI ( n  = 115), remitted MDD+MCI ( n  = 61), or without psychiatric disorders or cognitive impairment (healthy control participants; n  = 24). We estimated measures related to neurite density, orientation dispersion, and free water (isotropic volume fraction) using a biophysically plausible model (neurite orientation dispersion and density imaging)., Results: Results showed that increasing age was correlated with an increase in isotropic volume fraction and a decrease in orientation dispersion index, which is consistent with neuropathology dendritic loss. In addition, this relationship between age and increased isotropic volume fraction was more disrupted in the MCI group than in the remitted MDD or healthy control groups. However, the association between age and orientation dispersion index was similar for all 3 groups., Conclusions: The findings suggest that the neurite orientation dispersion and density imaging measures could be used to identify biological risk factors for Alzheimer's disease, signifying both conventional neurodegeneration observed with MCI and dendritic loss seen in MDD., (© 2023 The Authors.)

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found indirect effects of T2DM on volumes of other SVD and diffusion markers that were mediated by wmPVS: pWMH, dWMH, periventricular lacunes, and deep lacunes, and progression of deep lacunes over 1 year, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal mechanisms that mediate the impact of T2DM on cerebral small vessels., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Corinne Fischer reports financial support was provided by Canadian Institutes of Health Research. Corinne Fischer reports financial support was provided by Hoffmann-La Roche Limited. Corinne Fischer reports financial support was provided by Vielight Inc. Corinne Fischer reports financial support was provided by Novo Nordisk Inc. Corinne Fischer reports financial support was provided by National Institutes of Health. Corinne Fischer reports financial support was provided by Brain Canada Foundation. Corinne Fischer reports financial support was provided by The Weston Foundation. Corinne Fischer reports financial support was provided by St Michael's Hospital Foundation. David Grimes reports financial support was provided by Canadian Institutes of Health Research. David Grimes reports financial support was provided by Parkinson Society Canada. David Grimes reports financial support was provided by Brain Canada Foundation. David Grimes reports financial support was provided by Parkinson Research Consortium. David Grimes reports financial support was provided by EU Joint Programme Neurodegenerative Disease Research. David Grimes reports financial support was provided by University of Ottawa Brain and Mind Research Institute. David Grimes reports financial support was provided by National Institutes of Health. Sanjeev Kumar reports financial support was provided by Brain and Behavior Research Foundation. Sanjeev Kumar reports financial support was provided by National Institute of Health and Science on Aging. Sanjeev Kumar reports financial support was provided by BrightFocus Foundation. Sanjeev Kumar reports financial support was provided by Brain Canada Foundation. Sanjeev Kumar reports financial support was provided by Canadian Institutes of Health Research. Sanjeev Kumar reports financial support was provided by Canadian Consortium on Neurodegeneration in Aging. Sanjeev Kumar reports financial support was provided by Center for Aging and Brain Health Innovation. Sanjeev Kumar reports financial support was provided by Centre for Addiction and Mental Health. Sanjeev Kumar reports financial support was provided by University of Toronto. Sanjeev Kumar reports equipment, drugs, or supplies was provided by Soterix Medical Inc. Lisa Y. Xiong reports financial support was provided by Canadian Institutes of Health Research. Walter Swardfager reports financial support was provided by Canadian Institutes of Health Research. Walter Swardfager reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Walter Swardfager reports financial support was provided by Alzheimer's Association. Walter Swardfager reports financial support was provided by Alzheimer's Research UK. Walter Swardfager reports financial support was provided by The Michael J Fox Foundation. Walter Swardfager reports financial support was provided by Canada Research Chairs Program. Walter Swardfager reports financial support was provided by Ontario Ministry of Colleges and Universities. David Grimes reports a relationship with Sunovion Pharmaceuticals Canada Inc that includes consulting or advisory and speaking and lecture fees. David Grimes reports a relationship with Ipsen that includes: speaking and lecture fees. David Grimes reports a relationship with Paladin Labs Inc that includes: consulting or advisory. David Grimes reports a relationship with Allergan Canada that includes:. David Grimes reports a relationship with Cerevel Therapeutics Inc that includes: non-financial support. David Grimes reports a relationship with Genzyme Corporation that includes: non-financial support. David Grimes reports a relationship with Hoffmann-La Roche Limited that includes: non-financial support. David Grimes reports a relationship with UCB Biopharma Ltda that includes: non-financial support. Stephen Arnott reports a relationship with Indoc Research Canada that includes: consulting or advisory., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Alzheimer's dementia (AD) is associated with electroencephalography (EEG) abnormalities including in the power ratio of beta to theta frequencies. EEG studies in mild cognitive impairment (MCI) have been less consistent in identifying such abnormalities. One potential reason is not excluding the EEG aperiodic components, which are less associated with cognition than the periodic components. Here, we investigate whether aperiodic and periodic EEG components are disrupted differently in AD or MCI vs. healthy control (HC) individuals and whether a periodic based beta/theta ratio differentiates better MCI from AD and HC groups than a ratio based on the full spectrum., Methods: Data were collected from 44 HC (mean age (SD) = 69.1 (5.3)), 114 MCI (mean age (SD) = 72.2 (7.5)), and 41 AD (mean age (SD) = 75.7 (6.5)) participants. Aperiodic and periodic components and full spectrum EEG were compared among the three groups. Receiver operating characteristic curves obtained via logistic regression classifications were used to distinguish the groups. Last, we explored the relationships between cognitive performance and the beta/theta ratios based on the full or periodic spectrum., Results: Aperiodic EEG components did not differ among the three groups. In contrast, AD participants showed an increase in full spectrum and periodic relative powers for delta, theta, and gamma and a decrease for beta when compared to HC or MCI participants. As predicted, MCI group differed from HC participants on the periodic based beta/theta ratio (Bonferroni corrected p-value = 0.036) measured over the occipital region. Classifiers based on beta/theta power ratio in EEG periodic components distinguished AD from HC and MCI participants, and outperformed classifiers based on beta/theta power ratio in full spectrum EEG. Beta/theta ratios were comparable in their association with cognition., Conclusions: In contrast to a full spectrum EEG analysis, a periodic-based analysis shows that MCI individuals are different on beta/theta ratio when compared to healthy individuals. Focusing on periodic components in EEG studies with or without other biological markers of neurodegenerative diseases could result in more reliable findings to separate MCI from healthy aging, which would be valuable for designing preventative interventions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases., Methods: Five hundred thirteen participants with one of these conditions, i.e. Alzheimer's Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson's Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory - Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss., Results: Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson's disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities., Conclusions: In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed., (© 2023. The Author(s).)

Objective: Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function., Methods: We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD ( N  = 111), CVD ( N  = 148), PD ( N  = 136), FTD ( N  = 50) and ALS ( N  = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates., Results: Frequency of NPS varied across cohorts (χ 2 (4)  = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS ( H (4)  = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs ( F (4,461)  = 3.1, p  = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs., Conclusions: NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.

DNA analysis demonstrates that all seven individuals buried in an Early Iron Age barrow at Dolge njive, southeast Slovenia, are close biological relatives. Although group composition does not suggest strict adherence to a patrilineal or matrilineal kinship system, the funerary tradition appears highly gendered, with family links through both the male and female line being important in structuring communities. We explore the implications for our understandings of kinship and funerary practices in Early Iron Age southeast Europe.