Search

Importance: Traumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI., Objective: To assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals., Design, Setting, and Participants: This cross-sectional analysis used baseline data from the PREVENT Dementia program collected across 5 sites in the UK and Ireland between 2014 and 2020. Eligible participants were cognitively healthy midlife adults aged between 40 and 59 years. Data were analyzed between January 2023 and April 2024., Exposure: Lifetime TBI history was assessed using the Brain Injury Screening Questionnaire., Main Outcomes and Measures: Cerebral microbleeds and other markers of cerebral small vessel disease (white matter hyperintensities [WMH], lacunes, perivascular spaces) were assessed on 3T magnetic resonance imaging. Clinical measures were cognition, sleep, depression, gait, and cardiovascular disease (CVD) risk, assessed using Computerized Assessment of Information Processing (COGNITO), Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies Depression Scale, clinical interviews, and the Framingham Risk Score, respectively., Results: Of 617 participants (median [IQR] age, 52 [47-56] years; 380 female [61.6%]), 223 (36.1%) had a history of TBI. TBI was associated with higher microbleed count (β = 0.10; 95% CI, 0.01-0.18; P = .03), with a dose-response association observed with increasing number of TBI events (β = 0.05; 95% CI, 0.01-0.09; P = .03). Conversely, TBI was not associated with other measures of small vessel disease, including WMH. Furthermore, TBI moderated microbleed associations with vascular risk factors and clinical outcomes, such that associations were present only in the absence of TBI. Importantly, observations held when analyses were restricted to individuals reporting only mild TBI., Conclusions and Relevance: In this cross-sectional study of healthy middle-aged adults, detectable changes in brain imaging and clinical features were associated with remote, even mild, TBI in the general population. The potential contribution of vascular injury to TBI-related neurodegeneration presents promising avenues to identify potential targets, with findings highlighting the need to reduce TBI through early intervention and prevention in both clinical care and policymaking.

Background and Purpose: The Mediterranean diet (MedDiet) has been associated with reduced dementia incidence in several studies. It is important to understand if diet is associated with brain health in midlife, when Alzheimer's disease and related dementias are known to begin., Methods: This study used data from the PREVENT dementia programme. Three MedDiet scores were created (the Pyramid, Mediterranean Diet Adherence Screener [MEDAS] and MEDAS continuous) from a self-reported food frequency questionnaire. Primary outcomes were hippocampal volume and cube-transformed white matter hyperintensity volume. Secondary outcomes included cornu ammonis 1 and subiculum hippocampal subfield volumes, cortical thickness and measures of cognition. Sex-stratified analyses were run to explore differential associations between diet and brain health by sex. An exploratory path analysis was conducted to study if any associations between diet and brain health were mediated by cardiovascular risk factors for dementia., Results: In all, 504 participants were included in this analysis, with a mean Pyramid score of 8.10 (SD 1.56). There were no significant associations between any MedDiet scoring method and any of the primary or secondary outcomes. There were no differences by sex in any analyses and no significant mediation between the Pyramid score and global cognition by cardiovascular risk factors., Conclusions: Overall, this study did not find evidence for an association between the MedDiet and either neuroimaging or cognition in a midlife population study. Future work should investigate associations between the MedDiet and Alzheimer's disease and related dementias biomarkers as well as functional neuroimaging in a midlife population., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Aims: The Mediterranean diet (MedDiet) has been associated with better cardiovascular health in a number of studies. This study aimed to explore cross-sectional associations between MedDiet adherence in the PREVENT Dementia (PREVENT) programme, stratified by sex., Methods and Results: Three MedDiet scores were calculated (MEDAS, MEDAS continuous and Pyramid) alongside a Western diet score. We used linear regression and linear mixed effects models to test for associations between the MEDAS score and cardiovascular health. Propensity scores were calculated to strengthen causality inferences from the data, and used as covariates along with total energy intake and Western diet scores. Exploratory analysis repeated the linear regression models for each individual food component. This study included 533 participants, with a mean age 51.25 (±5.40) years, and a majority of women (60.0%). Women had higher MedDiet scores across all three scoring methods, had a lower Western diet score and consumed fewer total calories. Higher MedDiet scores were associated with lower blood pressure, body mass index (BMI) and lower cardiovascular risk scores. When stratified by sex, women had significant positive associations between MedDiet scores and lower blood pressure, BMI and glycemia, whereas men only had a significant association with lower BMI., Conclusion: There were significant associations between higher MedDiet scores and a number of cardiovascular health outcome measures. These associations were seen more consistently for women compared to men, which may have implications for the development of personalised nutritional recommendations to improve cardiovascular health., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Motoric cognitive risk (MCR) is a syndrome characterised by measured slow gait speed and self-reported cognitive complaints. MCR is a high-risk state for adverse health outcomes in older adults, particularly cognitive impairment and dementia. Previous studies have identified risk factors for MCR, but the effect of socioeconomic status has, to date, been insufficiently examined. This study explored the association between MCR and socioeconomic status, as determined by occupational social class and years of education., Methods: Some 692 community-based adults of the Lothian Birth Cohort 1936 (LBC1936), aged 70 years at baseline, were followed up after 6 years and classified into non-MCR and MCR groups. We applied logistic regression analyses adjusting for demographic, lifestyle, and health covariates to investigate the association between MCR and years of education and occupational social class, categorised into manual versus non-manual occupations., Results: MCR prevalence at age 76 years was 5.6% (95% CI 4.0-7.6). After multivariate adjustment, participants of lower socioeconomic status (manual occupation) had a greater than three-fold increased likelihood of MCR (adjusted odds ratio 3.55, 95% CI 1.46-8.74; p = 0.005) compared with those of higher socioeconomic status (non-manual occupation)., Conclusions: Working in a manual job earlier in life triples the risk of MCR later in life, regardless of education. Unravelling this association will likely reveal important pathophysiological mechanisms underlying MCR and may unearth modifiable risk factors which could be targeted to reduce the incidence of MCR and, ultimately, dementia. Policy and healthcare practice addressing dementia risks such as MCR in their social context and early in the lifecourse could be effective strategies for reducing health inequalities in older age., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Research suggests that personality traits are associated with mild cognitive impairment (MCI), dementia, and mortality risk, but the timing of when traits are most important in the progression to dementia and the extent to which they are associated with years of cognitive health span are unclear. This project applied secondary data analysis to the Rush Memory and Aging Project ( N = 1954; baseline M age = 80 years; 74% female) over up to 23 annual assessments. Multistate survival modeling examined the extent to which conscientiousness, neuroticism, and extraversion, assessed using the NEO Five Factor Inventory, were associated with transitions between cognitive status categories and death. Additionally, multinomial regression models estimated cognitive health span and total survival based on standard deviation units of personality traits. Adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4, personality traits were most important in the transition from no cognitive impairment (NCI) to MCI. For instance, higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI, hazard ratio (HR) = 0.78, 95% CI [0.72, 0.85] and higher neuroticism was associated with an increased risk of transitioning from NCI to MCI, HR = 1.12, 95% CI [1.04, 1.21]. Additional significant and nonsignificant results are discussed in the context of the existing literature. While personality traits were not associated with total longevity, individuals higher in conscientiousness and extraversion, and lower in neuroticism, had more years of cognitive health span, particularly female participants. These findings provide novel understanding of the simultaneous associations between personality traits and transitions between cognitive status categories and death, as well as cognitive health span and total longevity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The potential for future prevention of Alzheimer's disease and related dementias (ADRD) through healthy lifestyle change is spurring a positive brain health movement. However, most ADRD research continues to focus on mid- and later life. We lack evidence regarding risk exposure and protective factors in young adulthood, i.e., 18-39 years. Brain capital is an emerging framework that represents the combination of education, knowledge, skills, and optimal brain health that people accumulate over their lives. Building on this framework, we present a new model that focuses on optimizing brain health in young adulthood; namely, young adult brain capital. Increasing focus on younger populations is critical for developing citizens who are emotionally intelligent, resilient and can anticipate and cope with rapid changes in the world. By understanding the values that are key drivers and motivators for young adults, we can empower the next generation to become active agents in optimizing their brain health and reducing their risk for future ADRD.

We aimed to refine the hypothesis that motoric cognitive risk (MCR), a syndrome combining measured slow gait speed and self-reported cognitive complaints, is prognostic of incident dementia and other major causes of morbidity in older age. We propose mechanisms on the relationship between motor and cognitive function and describe a roadmap to validate these hypotheses. We systematically searched major electronic databases from inception to August 2021 for original longitudinal cohort studies of adults aged ≥60 years that compared an MCR group to a non-MCR group with any health outcome. Fifteen cohorts were combined by meta-analysis. Participants with MCR were at an increased risk of cognitive impairment (adjusted hazard ratio [aHR] 1.76, 95% CI 1.49-2.08; I 2  = 24.9%), dementia (aHR 2.12, 1.85-2.42; 33.1%), falls (adjusted Relative Risk 1.38, 1.15-1.66; 62.1%), and mortality (aHR 1.49, 1.16-1.91; 79.2%). The prognostic value of MCR is considerable and mechanisms underlying the syndrome are proposed., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: Motoric Cognitive Risk (MCR) is a gait-based predementia syndrome that is easy to measure and prognostic of dementia and falls. We aimed to examine the prevalence and risk factors for MCR, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults without dementia., Methods: In this longitudinal prospective study, we classified 690 participants (mean [SD] age 76.3 [0.8] years; wave 3) of the Lothian Birth Cohort 1936 (LBC1936) into non-MCR or MCR groups. We examined their baseline (age 69.5 [0.8] years; wave 1) risk factors for MCR at waves 3, 4, and 5 (6, 9, and 12 years later respectively)., Results: MCR prevalence rate ranged from 5.3% to 5.7% across the three waves. The presence of MCR was associated with older baseline age (6 and 9 years later), lower occupational socioeconomic status (6 years later), and worse scores in a range of tests of executive function (6, 9 and 12 years later). Approximately 46% of the MCR group also had Mild Cognitive Impairment, and almost everyone in the MCR group had either Prefrailty or Frailty., Conclusions: The prevalence of MCR in this Scottish cohort is lower than the pooled global average, possibly reflecting the general good health of the LBC cohort. However, it is higher than the prevalence in two neighbouring countries' cohorts, which may reflect the younger average ages of those cohorts. Future LBC1936 research should assess the risk factors associated with MCR to validate previous findings and analyse novel predictive factors, particularly socioeconomic status., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Considerable overlap exists between the risk factors of dementia and cerebral small vessel disease (SVD). However, studies remain limited to older cohorts wherein pathologies of both dementia (e.g. amyloid) and SVD (e.g. white matter hyperintensities) already co-exist. In younger asymptomatic adults, we investigated differential associations and interactions of modifiable and non-modifiable inherited risk factors of (future) late-life dementia to (present-day) mid-life SVD., Methods: Cognitively healthy middle-aged adults (aged 40-59; mean 51.2 years) underwent 3T MRI (n = 630) as part of the PREVENT-Dementia study. To assess SVD, we quantified white matter hyperintensities, enlarged perivascular spaces, microbleeds, lacunes, and computed composite scores of SVD burden and subtypes of hypertensive arteriopathy and cerebral amyloid angiopathy (CAA). Non-modifiable (inherited) risk factors were APOE4 status and parental family history of dementia. Modifiable risk factors were derived from the 2020 Lancet Commission on dementia prevention (early/midlife: education, hypertension, obesity, alcohol, hearing impairment, head injuries). Confirmatory factor analysis (CFA) was used to evaluate the latent variables of SVD and risk factors. Structural equation modelling (SEM) of the full structural assessed associations of SVD with risk factors and APOE4*risk interaction., Results: In SEM, the latent variable of global SVD related to the latent variable of modifiable midlife risk SVD (β = 0.80, p = .009) but not non-modifiable inherited risk factors of APOE4 or family history of dementia. Interaction analysis demonstrated that the effect of modifiable risk on SVD was amplified in APOE4 non-carriers (β = - 0.31, p = .009), rather than carriers. These associations and interaction effects were observed in relation to the SVD subtype of hypertensive arteriopathy, rather than CAA. Sensitivity analyses using separate general linear models validated SEM results., Conclusions: Established modifiable risk factors of future (late-life) dementia related to present-day (mid-life) SVD, suggesting that early lifestyle modifications could potentially reduce rates of vascular cognitive impairment attributed to SVD, a major 'silent' contributor to global dementia cases. This association was amplified in APOE4 non-carriers, suggesting that lifestyle modifications could be effective even in those with genetic predisposition to dementia., (© 2022. The Author(s).)

Background: Cognitive dispersion, or inconsistencies in performance across cognitive domains, has been posited as a cost-effective tool to predict conversion to dementia in older adults. However, there is a dearth of studies exploring cognitive dispersion in the oldest-old (>80 years) and its relationship to dementia incidence., Objective: The main aim of this study was to examine whether higher cognitive dispersion at baseline was associated with dementia incidence within an 8-year follow-up of very old adults, while controlling for established risk factors and suggested protective factors for dementia., Methods: Participants (n = 468) were from the Origins of Variance in the Old-Old: Octogenarian Twins study, based on the Swedish Twin Registry. Cox regression analyses were performed to assess the association between baseline cognitive dispersion scores and dementia incidence, while controlling for sociodemographic variables, ApoEe4 carrier status, co-morbidities, zygosity and lifestyle engagement scores. An additional model included a composite of average cognitive performance., Results: Cognitive dispersion and ApoEe4 were significantly associated with dementia diagnosis. These variables remained statistically significant when global cognitive performance was entered into the model. Likelihood ratio tests revealed that cognitive dispersion and cognitive composite scores entered together in the same model was superior to either predictor alone in the full model., Conclusions: The study underscores the usefulness of cognitive dispersion metrics for dementia prediction in the oldest-old and highlights the influence of ApoEe4 on cognition in very late age. Our findings concur with others suggesting that health and lifestyle factors pose little impact upon cognition in very advanced age., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Cerebral small vessel disease (SVD) and inflammation are increasingly recognized as key contributors to Alzheimer's disease (AD), although the timing, trajectory, and relation between them early in the disease process is unclear. Therefore, to investigate very early-stage changes, we compared 158 healthy midlife adults with and without inherited AD predisposition (APOE4 carriership (38% positive), parental family history (FH) of dementia (54% positive)) on markers of SVD (white matter hyperintensities (WMH), cerebral microbleeds), and inflammation (C-reactive protein (CRP), fibrinogen), cross-sectionally and longitudinally over two years. While WMH severity was comparable between groups at baseline, longitudinal progression of WMH was greater in at-risk groups (APOE4+ and FH+). Topographically, APOE4 was associated exclusively with deep, but not periventricular, WMH progression after adjusting for FH. Conversely, APOE4 carriers displayed lower CRP levels than noncarriers, but not fibrinogen. Furthermore, interaction analysis showed that FH moderated the effect of SVD and inflammation on reaction time, an early feature of SVD, but not episodic memory or executive function. Findings suggest that vascular and inflammatory changes could occur decades before dementia onset, and may be of relevance in predicting incipient clinical progression., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Whether in the context of monitoring disease progression or in assessing the effects of interventions, a major challenge in dementia research is determining when an individual has undergone meaningful change in symptoms and other relevant outcomes such as cognitive test performance. The challenge lies in differentiating genuine improvement or deterioration from change in scores due to random and systematic error. BODY: In this review, we discuss the advantages and limitations of available methods for assessing individual-level change in the context of key challenges, including imperfect and differential reliability of scores, and practice effects. We discuss indices of reliable change and the use of composite and item response theory (IRT) scores., Conclusion: We conclude that IRT-based approaches hold particular promise because they have the flexibility to accommodate solutions to a wide range of issues that influence the accuracy of judgements of meaningful change. We close by discussing the practical implications of adopting IRT-based approaches.

Background: Telephone and videoconference administration of cognitive tests introduce additional sources of variance compared to in-person testing. Reviews of test-retest reliability have included mixed neurocognitive and psychiatric populations with limited consideration of methodological and statistical contributions., Objective: We reviewed reliability estimates from comparison studies of older adults with and without dementia, considering test-retest analyses and study methods., Methods: Medline, Embase, PsycINFO, and Web of Science were systematically searched from 1 January 2000 to 9 June 2020 for original articles comparing telephone or videoconference administered cognitive instruments to in-person administration in older adults with and without dementia or mild cognitive impairment., Results: Of 4,125 articles, 23 were included: 11 telephone (N = 2 dementia cohorts) and 12 videoconference (N = 4 dementia cohorts). Telephone administered subtest scores trended in the same direction as in-person with comparable means. Person-level data were scarce. Data on dementia was only available for MMSE, with resulting subtle modality bias. MMSE, SMMSE, Letter Fluency, and HVLT-R in healthy to mild-moderate Alzheimer's disease were particularly reliable for videoconference administration. Other tests show promise but require more observations and comprehensive analyses. Most studies used high-speed stable videoconferencing hardware resulting in a lack of ecological validity for home administration., Conclusion: Remote administration is often consistent with in-person administration but variable and limited at the person/test level. Improved statistical design and inclusion of dementia related cohorts in telephone studies is recommended. Reliability evidence is stronger for videoconferencing but with limited applicability to home administration and severe dementia. Improved reporting of administrative procedures is recommended.

Background: To date, dementia prediction models have been exclusively developed and tested in high-income countries (HICs). However, most people with dementia live in low-income and middle-income countries (LMICs), where dementia risk prediction research is almost non-existent and the ability of current models to predict dementia is unknown. This study investigated whether dementia prediction models developed in HICs are applicable to LMICs., Methods: Data were from the 10/66 Study. Individuals aged 65 years or older and without dementia at baseline were selected from China, Cuba, the Dominican Republic, Mexico, Peru, Puerto Rico, and Venezuela. Dementia incidence was assessed over 3-5 years, with diagnosis according to the 10/66 Study diagnostic algorithm. Discrimination and calibration were tested for five models: the Cardiovascular Risk Factors, Aging and Dementia risk score (CAIDE); the Study on Aging, Cognition and Dementia (AgeCoDe) model; the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI); the Brief Dementia Screening Indicator (BDSI); and the Rotterdam Study Basic Dementia Risk Model (BDRM). Models were tested with use of Cox regression. The discriminative accuracy of each model was assessed using Harrell's concordance (c)-statistic, with a value of 0·70 or higher considered to indicate acceptable discriminative ability. Calibration (model fit) was assessed statistically using the Grønnesby and Borgan test., Findings: 11 143 individuals without baseline dementia and with available follow-up data were included in the analysis. During follow-up (mean 3·8 years [SD 1·3]), 1069 people progressed to dementia across all sites (incidence rate 24·9 cases per 1000 person-years). Performance of the models varied. Across countries, the discriminative ability of the CAIDE (0·52≤c≤0·63) and AgeCoDe (0·57≤c≤0·74) models was poor. By contrast, the ANU-ADRI (0·66≤c≤0·78), BDSI (0·62≤c≤0·78), and BDRM (0·66≤c≤0·78) models showed similar levels of discriminative ability to those of the development cohorts. All models showed good calibration, especially at low and intermediate levels of predicted risk. The models validated best in Peru and poorest in the Dominican Republic and China., Interpretation: Not all dementia prediction models developed in HICs can be simply extrapolated to LMICs. Further work defining what number and which combination of risk variables works best for predicting risk of dementia in LMICs is needed. However, models that transport well could be used immediately for dementia prevention research and targeted risk reduction in LMICs., Funding: National Institute for Health Research, Wellcome Trust, WHO, US Alzheimer's Association, and European Research Council., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To model trajectories of visuospatial reasoning measured using Kohs Block Design test under realistic missing data assumptions and evaluate their association with hazard of death., Methods: A joint longitudinal-survival model was used to estimate trajectories of visuospatial reasoning under a missing not at random assumption of participants from the Origins of Variance in the Old-Old: Octogenarian Twins study. Sensitivity analyses to missing data assumptions were conducted., Results: Visuospatial reasoning declined at constant rate. Baseline age, dementia status, education, and history of stroke were associated with visuospatial reasoning performance, but only dementia was associated with its rate of decline. Importantly, our results demonstrated an association between poorer visuospatial reasoning and increased hazard of death. Baseline age and sex were associated with risk of death., Discussion: We confirmed an association between visuospatial reasoning and death under plausible missing data assumptions.

Purpose of Review: To date, most research in dementia has focused either on the identification of dementia risk prediction or on understanding changes and predictors experienced by individuals before diagnosis. Despite little is known about how individuals change after dementia diagnosis, there is agreement that changes occur over different time scales and are multidomain. In this study, we present an overview of the literature regarding the longitudinal course of dementia., Recent Findings: Our review suggests the evidence is scarce and findings reported are often inconsistent. We identified large heterogeneity in dementia trajectories, risk factors considered and modelling approaches employed. The heterogeneity of dementia trajectories also varies across outcomes and domains investigated., Summary: It became clear that dementia progresses very differently, both between and within individuals. This implies an average trajectory is not informative to individual persons and this needs to be taken into account when communicating prognosis in clinical care. As persons with dementia change in many more ways during their patient journey, heterogeneous disease progressions are the result of disease and patient characteristics. Prognostic models would benefit from including variables across a number of domains. International coordination of replication and standardization of the research approach is recommended.

Background: In a previous report, we used latent class analysis (LCA) to identify natural subgroups of older adults in the Einstein Aging Study (EAS) based on neuropsychological performance. These subgroups differed in demographics, genetic profile, and prognosis. Herein, we assess the generalizability of these findings to an independent sample, the Rush Memory and Aging Project (MAP), which used an overlapping, but distinct neuropsychological battery., Objective: Our aim was to identify the association of natural subgroups based on neuropsychological performance in the MAP cohort with incident dementia and compare them with the associations identified in the EAS., Methods: MAP is a community-dwelling cohort of older adults living in the northeastern Illinois, Chicago. Latent class models were applied to baseline scores of 10 neuropsychological measures across 1,662 dementia-free MAP participants. Results were compared to prior findings from the EAS., Results: LCA resulted in a 5-class model: Mixed-Domain Impairment (n = 71, 4.3%), Memory-specific-Impairment (n = 274, 16.5%), Average (n = 767, 46.1%), Frontal Impairment (n = 222, 13.4%), and a class of Superior Cognition (n = 328, 19.7%). Similar to the EAS, the Mixed-Domain Impairment, the Memory-Specific Impairment, and the Frontal Impairment classes had higher risk of incident Alzheimer's disease when compared to the Average class. By contrast, the Superior Cognition had a lower risk of Alzheimer's disease when compared to the Average class., Conclusions: Natural cognitive subgroups in MAP are similar to those identified in EAS. These similarities, despite study differences in geography, sampling strategy, and cognitive tests, suggest that LCA is capable of identifying classes that are not limited to a single sample or a set of cognitive tests.

Introduction: This study examines the role of educational attainment, an indicator of cognitive reserve, on transitions in later life between cognitive states (normal Mini-Mental State Examination (MMSE), mild MMSE impairment, and severe MMSE impairment) and death., Methods: Analysis of six international longitudinal studies was performed using a coordinated approach. Multistate survival models were used to estimate the transition patterns via different cognitive states. Life expectancies were estimated., Results: Across most studies, a higher level of education was associated with a lower risk of transitioning from normal MMSE to mild MMSE impairment but was not associated with other transitions. Those with higher levels of education and socioeconomic status had longer nonimpaired life expectancies., Discussion: This study highlights the importance of education in later life and that early life experiences can delay later compromised cognitive health. This study also demonstrates the feasibility and benefit in conducting coordinated analysis across multiple studies to validate findings., (Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Older adults who ultimately develop dementia experience accelerated cognitive decline long before diagnosis. A similar acceleration in cognitive decline occurs in the years before death as well. To evaluate preclinical and terminal cognitive decline, past researchers have incorporated change points in their analyses of longitudinal data, identifying point estimates of how many years prior to diagnosis or death that decline begins to accelerate. The current systematic review aimed to summarize the published literature on preclinical and terminal change points in relation to mild cognitive impairment (MCI), dementia, and death, identifying the order in which cognitive and neurological outcomes decline and factors that modify the onset and rate of decline. A systematic search protocol yielded 35 studies, describing 16 longitudinal cohorts, modeling change points for cognitive and neurological outcomes preceding MCI, dementia, or death. Change points for cognitive abilities ranged from 3-7 years prior to MCI diagnosis, 1-11 years prior to dementia diagnosis, and 3-15 years before death. No sequence of decline was observed preceding MCI or death, but the following sequence was tentatively accepted for Alzheimer's disease: verbal memory, visuospatial ability, executive functions and fluency, and last, verbal IQ. Some of the modifiers of the onset and rate of decline examined by previous researchers included gender, education, genetics, neuropathology, and personality. Change point analyses evidence accelerated decline preceding MCI, dementia, and death, but moderators of the onset and rate of decline remain ambiguous due to between-study modeling differences, and coordinated analyses may improve comparability across future studies. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objective: Cognitive performance shows a marked deterioration in close proximity to death, as postulated by the terminal decline hypothesis. The effect of education on the rate of terminal decline in the oldest people (i.e. persons 85+ years) has been controversial and not entirely understood. In the current study, we investigated the rate of decline prior to death with a special focus on the role of education and socioeconomic position, in two European longitudinal studies of ageing: the Origins of Variance in the Old-Old: Octogenarian Twins (OCTO-Twin) and the Newcastle 85+ study., Methods: A process-based approach was used in which individuals' cognitive scores were aligned according to distance to death. In a coordinated analysis, multilevel models were employed to examine associations between different markers of cognitive reserve (education and socioeconomic position) and terminal decline using the mini-mental state examination (MMSE), controlling for age at baseline, sex, dementia incidence and time to death from the study entry to the time of death within each cohort., Results: The current findings suggest that education was positively associated with higher MMSE scores prior to death in the OCTO-Twin, but not in the Newcastle 85+ study, independent of socioeconomic position and other factors such as baseline age, sex and time to death from the study entry. However, education was not associated with the rate of terminal decline in both of these studies., Conclusions: Our results offer only partial support to the cognitive reserve hypothesis and cognitive performance prior to death., (© 2015 The Authors International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.)

Purpose of Review: A key priority in dementia research is the development of tools to identify individuals at high risk of dementia. This is important to prevent or delay dementia onset and as we move towards personalized medicine., Recent Findings: Numerous models (n > 50) for predicting dementia have been developed. These vary in the number (0 to 20+) and type (e.g. demographics, health, neuropsychological, and genetic) of predictor variables used for risk calculation, follow-up length (1-20 years) and age at screening (mid vs laterlife). Evaluation of the models shows that most have moderate-to-poor predictive accuracy. Few have been externally validated, raising questions about their generalizability outside the cohorts from which they were developed. The results highlight that if additional models are proposed the field will be overwhelmed with many competing risk models, making it difficult to reach consensus on which is best., Summary: Numerous models for predicting dementia have been proposed but are limited by a lack of external validation and evaluation of economic impact. Innovative methods and data designs may be needed to improve derivation of dementia risk scores. Having a method for predicting dementia risk could transform medical research and allow for earlier testing of intervention strategies.

Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia. However, previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline. Herein, we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline. We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium. The Vantaa 85+ study examined 553 individuals (92% of those eligible) aged ≥85 years at baseline, 3, 5, 8 and 10 years. Brain autopsy was performed in 52%. Fixed and random-effects regression models were used to assess associations between (i) delirium and incident dementia and (ii) decline in Mini-Mental State Examination scores in the whole group. The relationship between dementia and common neuropathological markers (Alzheimer-type, infarcts and Lewy-body) was modelled, stratified by history of delirium. Delirium increased the risk of incident dementia (odds ratio 8.7, 95% confidence interval 2.1-35). Delirium was also associated with worsening dementia severity (odds ratio 3.1, 95% confidence interval 1.5-6.3) as well as deterioration in global function score (odds ratio 2.8, 95% confidence interval 1.4-5.5). In the whole study population, delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year (95% confidence interval 0.11-1.89) than those with no history of delirium. In individuals with dementia and no history of delirium (n = 232), all pathologies were significantly associated with dementia. However, in individuals with delirium and dementia (n = 58), no relationship between dementia and these markers was found. For example, higher Braak stage was associated with dementia when no history of delirium (odds ratio 2.0, 95% confidence interval 1.1-3.5, P = 0.02), but in those with a history of delirium, there was no significant relationship (odds ratio 1.2, 95% confidence interval 0.2-6.7, P = 0.85). This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid, apolipoprotein ε status, presence of infarcts, α-synucleinopathy and neuronal loss in substantia nigra. These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old. However, in this study, the relationship did not appear to be mediated by classical neuropathologies associated with dementia.

Objectives: Investigate the impact of the changes in eligibility within England and Wales (E&W) for prescription within the UK National Health Service for treatment of Alzheimer's disease (AD)., Methods: A population-based study in England and Wales with 13,004 individuals measured with MMSE at baseline was used to examine the distributions of individuals within eligibility criteria. Information obtained from informants enabled classification of the study defined dementia cases to ICD10 diagnosis of subtype (AD, dementia with vascular risk, both or other)., Results: Fifty six per cent of dementia patients (representing 323,000 individuals in E&W) fall into the new MMSE criteria band. A further 120,000, 20% of dementia patients, are estimated to have disease that is considered too mild for treatment. Further examination of type of dementia showed that those with mixed AD and vascular dementia had similar proportions of dementia cases within the treatable MMSE group as the subgroup with AD alone, though with mixed disease individuals more often score below the lower threshold. There is substantial instability in the eligibility groupings over a short time period., Conclusions: The population impact of new NICE criteria of excluding high MMSE scores is to exclude one in five individuals with AD and a further one in ten of those with a mixed disease. Changing the guidance has almost balanced the loss of treatment for the high MMSE group (13%) with the introduction of treatment for those scoring 10/11 (11%)., ((c) 2009 John Wiley & Sons, Ltd.)

BackgroundThe existing literature suggests that impaired olfaction may be an early marker for cognitive decline. Tracking the earliest stages of the progression to dementia is paramount, and yet the importance of olfactory ability throughout cognitive states and death remains unclear.MethodsDrawing data from the Rush Memory and Aging Project (N = 1 501; 74% female), olfactory ability was assessed using the Brief Smell Identification Test (range = 0-16), while cognitive states (unimpaired, mild cognitive impairment [MCI], and dementia) were determined using a 3-step neuropsychological diagnostic protocol at up to 15 annual occasions. Multistate survival models simultaneously estimated the association of olfactory ability on transitions through cognitive states and death, while multinomial regression models estimated cognitively unimpaired and total life expectancies.ResultsHigher olfactory scores were associated with a reduced risk of transitioning from unimpaired cognition to MCI (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.82-0.88) and from MCI to dementia (HR = 0.89, 95% CI = 0.86-0.93), indicating that 1-unit increase in olfactory scores was associated with an approximate 14% and 11% reduction in risk, respectively. Additionally, higher olfactory scores were associated with a greater likelihood of transitioning backward from MCI to unimpaired cognition (HR = 1.07, 95% CI = 1.02-1.12). Furthermore, higher baseline olfactory scores were associated with more years of longevity without cognitive impairment. However, olfaction was not associated with the transition to death when accounting for transitions through cognitive states.ConclusionsFindings suggest that higher olfactory identification scores are associated with a decreased risk of transitioning to impaired cognitive states and that associations between olfaction and mortality may occur primarily through the pathway of neurodegeneration.

BackgroundGiven increasing incidence of cognitive impairment and dementia, further understanding of modifiable factors contributing to increased healthspan is crucial. Extensive literature provides evidence that physical activity (PA) delays the onset of cognitive impairment; however, it is unclear whether engaging in PA in older adulthood is sufficient to influence progression through cognitive status categories.MethodApplying a coordinated analysis approach, this project independently analyzed 14 longitudinal studies (NTotal = 52 039; mean baseline age across studies = 69.9-81.73) from North America and Europe using multistate survival models to estimate the impact of engaging in PA on cognitive status transitions (nonimpaired, mildly impaired, severely impaired) and death. Multinomial regression models were fit to estimate life expectancy (LE) based on American PA recommendations. Meta-analyses provided the pooled effect sizes for the role of PA on each transition and estimated LEs.ResultsControlling for baseline age, sex, education, and chronic conditions, analyses revealed that more PA is significantly associated with decreased risk of transitioning from nonimpaired to mildly impaired cognitive functioning and death, as well as substantially longer LE. Results also provided evidence for a protective effect of PA after onset of cognitive impairment (eg, decreased risk of transitioning from mild-to-severe cognitive impairment; increased likelihood of transitioning backward from severe-to-mild cognitive impairment), though between-study heterogeneity suggests a less robust association.ConclusionsThese results yield evidence for the importance of engaging in PA in older adulthood for cognitive health, and a rationale for motivating older adults to engage consistently in PA.

Objectives: To investigate the availability of Alzheimer's Centers (ACs) in US hospitals. Methods: Utilizing the American Hospital Association Annual Survey, Area Health Resource File, and US Census (n = 3251), we employed multivariable logistic regression to examine hospital, county, and regional predictors of AC availability. Results: Large hospitals (>399 beds) had approximately 14 times higher odds of having an AC than small hospitals (<50 beds; OR = 14.0; 95% CI = 6.44 – 30.46). Counties with a higher proportion of Latino residents, relative to non-Latino Whites, had lower odds of having an AC (OR =.05; 95% CI =.01 –.41). Northeastern (OR = 1.92; 95% CI = 1.15 – 3.22) and Midwestern (OR = 2.12; 95% CI = 1.34 – 3.37) hospitals had higher odds of having an AC than Southern hospitals. Discussion: To address dementia needs and disparities, investment in a national infrastructure is critical. [ABSTRACT FROM AUTHOR]

We aimed to refine the hypothesis that motoric cognitive risk (MCR), a syndrome combining measured slow gait speed and self‐reported cognitive complaints, is prognostic of incident dementia and other major causes of morbidity in older age. We propose mechanisms on the relationship between motor and cognitive function and describe a roadmap to validate these hypotheses. We systematically searched major electronic databases from inception to August 2021 for original longitudinal cohort studies of adults aged ≥60 years that compared an MCR group to a non‐MCR group with any health outcome. Fifteen cohorts were combined by meta‐analysis. Participants with MCR were at an increased risk of cognitive impairment (adjusted hazard ratio [aHR] 1.76, 95% CI 1.49–2.08; I2 = 24.9%), dementia (aHR 2.12, 1.85–2.42; 33.1%), falls (adjusted Relative Risk 1.38, 1.15–1.66; 62.1%), and mortality (aHR 1.49, 1.16–1.91; 79.2%). The prognostic value of MCR is considerable and mechanisms underlying the syndrome are proposed. [ABSTRACT FROM AUTHOR]

A biomarker associated with cognition in neurodegenerative dementias would aid in the early detection of disease progression, complement clinical staging and act as a surrogate endpoint in clinical trials. The current systematic review evaluates the association between cerebrospinal fluid protein markers of synapse loss and neuronal injury and cognition. We performed a systematic search which revealed 67 studies reporting an association between cerebrospinal fluid markers of interest and neuropsychological performance. Despite the substantial heterogeneity between studies, we found some evidence for an association between neurofilament‐light and worse cognition in Alzheimer's diseases, frontotemporal dementia and typical cognitive ageing. Moreover, there was an association between cerebrospinal fluid neurogranin and cognition in those with an Alzheimer's‐like cerebrospinal fluid biomarker profile. Some evidence was found for cerebrospinal fluid neuronal pentraxin‐2 as a correlate of cognition across dementia syndromes. Due to the substantial heterogeneity of the field, no firm conclusions can be drawn from this review. Future research should focus on improving standardization and reporting as well as establishing the importance of novel markers such as neuronal pentraxin‐2 and whether such markers can predict longitudinal cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Previous studies on the relationship between anticholinergic drugs and dementia have reported heterogeneous results. This variability could be due to different anticholinergic scales and differential effects of distinct classes of drugs. Methods: Using Cox proportional hazards models, we computed the association between annual anticholinergic burden (AChB) and the risk of dementia inUK Biobank with linked general practitioner prescription records between the years 2000 and 2015 (n = 171,775). Results:AChB according to most anticholinergic scales (standardized odds ratio range: 1.027-1.125) and the slope of the AChB trajectory (hazard ratio = 1.094; 95% confidence interval: 1.068-1.119) were predictive of dementia. However, the association between AChB and dementia held only for some classes of drugs, especially antidepressants, antiepileptics, and antidiuretics. Discussion: The heterogeneity in previous findings may partially be due to different effects for different classes of drugs. Future studies should establish differences in more detail and further examine the practicality of a general measure of AChB relating to the risk of dementia. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests vascular dysregulation in preclinical Alzheimer's disease. In this study, cerebral hemodynamics and their coupling with cognition in middle-aged apolipoprotein ε4 carriers (APOEε4+) were investigated. Longitudinal 3 T T1-weighted and arterial spin labelling MRI data from 158 participants (40–59 years old) in the PREVENT-Dementia study were analysed (125 two-year follow-up). Cognition was evaluated using the COGNITO battery. Cerebral blood flow (CBF) and cerebrovascular resistance index (CVRi) were quantified for the flow territories of the anterior, middle and posterior cerebral arteries. CBF was corrected for underlying atrophy and individual hematocrit. Hemodynamic measures were the dependent variables in linear regression models, with age, sex, years of education and APOEε4 carriership as predictors. Further analyses were conducted with cognitive outcomes as dependent variables, using the same model as before with additional APOEε4 × hemodynamics interactions. At baseline, APOEε4+ showed increased CBF and decreased CVRi compared to non-carriers in the anterior and middle cerebral arteries, suggestive of potential vasodilation. Hemodynamic changes were similar between groups. Interaction analysis revealed positive associations between CBF changes and performance changes in delayed recall (for APOEε4 non-carriers) and verbal fluency (for APOEε4 carriers) cognitive tests. These observations are consistent with neurovascular dysregulation in middle-aged APOEε4+. [ABSTRACT FROM AUTHOR]

Background and Objectives Grip strength is a reliable marker of biological vitality and it typically demonstrates an expected decline in older adults. According to the common-cause hypothesis, there is also a significant association between cognitive and physical function in older adults. Some specific cognitive functions have been shown to be associated with grip strength trajectories with most research solely focused on cutoff points or mean cognitive performance. In the present study, we examine whether a measure of cognitive dispersion might be more informative. We therefore used an index that quantifies dispersion in cognitive scores across multiple cognitive tests, shown to be associated with detrimental outcomes in older adults. Research Design and Methods Using repeated grip strength measures from men and women aged 80 and older, free of dementia in the OCTO-Twin study, we estimated aging-related grip strength trajectories. We examined the association of cognitive dispersion and mean cognitive function with grip strength level and aging-related rate of change, accounting for known risk factors. Results Cognitive dispersion was associated with grip strength trajectories in men and the association varied by mean cognitive performance, whereas we found no association in women. Discussion and Implications Our results provide evidence of a sex-specific vitality association between cognitive dispersion and aging-related trajectories of grip strength. Our results support the call for integration of sex and gender in health promotion and intervention research. [ABSTRACT FROM AUTHOR]

Background: The genetic variant rs9923231 (VKORC1) is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has been linked in a gene-based test to dementia/Alzheimer's disease in the parents of participants, with suggestive evidence for an association for rs9923231 (p = 1.8×10-7), which was included in the genome-wide significant KAT8 locus.Objective: Our study aimed to investigate whether the relationship between rs9923231 and dementia persists only for certain dementia sub-types, and if those taking warfarin are at greater risk.Methods: We used logistic regression and data from 238,195 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use.Results: Parental history of dementia, APOE variant, atrial fibrillation, diabetes, hypertension, and hypercholesterolemia all had strong associations with vascular dementia (p < 4.6×10-6). The T-allele in rs9923231 was linked to a lower warfarin dose (βperT - allele = -0.29, p < 2×10-16) and risk of vascular dementia (OR = 1.17, p = 0.010), but not other dementia sub-types. However, the risk of vascular dementia was not affected by warfarin use in carriers of the T-allele.Conclusion: Our study reports for the first time an association between rs9923231 and vascular dementia, but further research is warranted to explore potential mechanisms and specify the relationship between rs9923231 and features of vascular dementia. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) describes a borderland between healthy cognition and dementia. Progression to and reversion from MCI is relatively common but more research is required to understand the factors affecting this fluidity and improve clinical care interventions.Objective: We explore these transitions in MCI status and their predictive factors over a six-year period in a highly-phenotyped longitudinal study, the Lothian Birth Cohort 1936.Methods: MCI status was derived in the LBC1936 at ages 76 (n = 567) and 82 years (n = 341) using NIA-AA diagnostic guidelines. Progressions and reversions between healthy cognition and MCI over the follow-up period were assessed. Multinomial logistic regression assessed the effect of various predictors on the likelihood of progressing, reverting, or maintaining cognitive status.Results: Of the 292 participants who completed both time points, 41 (14%) participants had MCI at T1 and 56 (19%) at T2. Over the follow-up period, 74%remained cognitively healthy, 12%transitioned to MCI, 7%reverted to healthy cognition, and 7%maintained their baseline MCI status. Findings indicated that membership of these transition groups was affected by age, cardiovascular disease, and number of depressive symptoms.Conclusion: Findings that higher baseline depressive symptoms increase the likelihood of reverting from MCI to healthy cognition indicate that there may be an important role for the treatment of depression for those with MCI. However, further research is required to identify prevention strategies for those at high risk of MCI and inform effective interventions that increase the likelihood of reversion to, and maintenance of healthy cognition. [ABSTRACT FROM AUTHOR]

Background: Air pollution has been consistently linked with dementia and cognitive decline. However, it is unclear whether risk is accumulated through long-term exposure or whether there are sensitive/critical periods. A key barrier to clarifying this relationship is the dearth of historical air pollution data.Objective: To demonstrate the feasibility of modelling historical air pollution data and using them in epidemiologicalmodels.Methods: Using the EMEP4UK atmospheric chemistry transport model, we modelled historical fine particulate matter (PM2.5) concentrations for the years 1935, 1950, 1970, 1980, and 1990 and combined these with contemporary modelled data from 2001 to estimate life course exposure in 572 participants in the Lothian Birth Cohort 1936 with lifetime residential history recorded. Linear regression and latent growth models were constructed using cognitive ability (IQ) measured by the Moray House Test at the ages of 11, 70, 76, and 79 years to explore the effects of historical air pollution exposure. Covariates included sex, IQ at age 11 years, social class, and smoking.Results: Higher air pollution modelled for 1935 (when participants would have been in utero) was associated with worse change in IQ from age 11-70 years (β = -0.006, SE = 0.002, p = 0.03) but not cognitive trajectories from age 70-79 years (p > 0.05). There was no support for other critical/sensitive periods of exposure or an accumulation of risk (all p > 0.05).Conclusion: The life course paradigm is essential in understanding cognitive decline and this is the first study to examine life course air pollution exposure in relation to cognitive health. [ABSTRACT FROM AUTHOR]

Background: Conceptualizing cognitive aging as a step-sequential process is useful in identifying particular stages of cognitive function and impairment.Objective: We applied latent transition analysis (LTA) to determine 1) whether the underlying structure of cognitive profiles found at every measurement occasion are uniform across three waves of assessment, 2) whether class-instability is predictive of distal outcomes, and 3) whether class-reversions from impaired to non-impaired using latent modelling is lower than when using clinical criteria of mild cognitive impairment (MCI).Methods: A mover-stayer LTA model with dementia as a distal outcome was specified to model transitions of ten neuropsychological measures over three annual waves in the Rush Memory and Aging Project (n = 1,661). The predictive validity of the mover-stayer status for incident Alzheimer's disease (AD) was then assessed.Results: We identified a five-class model across the three time-points: Mixed-Domain Impairment, Memory-Specific Impairment, Frontal Impairment, Average, and Superior Cognition. None of the individuals in the Impairment classes reverted to the Average or Superior classes. Conventional MCI classification identified 26.4% and 14.1% at Times 1 and 2 as false-positive cases. "Movers" had 87% increased risk of developing dementia compared to those classified as "Stayers".Conclusion: Our findings support the use of latent variable modelling that incorporates comprehensive neuropsychological assessment to identify and classify cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods: We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results: A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95–0.99]), high education (OR = 1.64 [1.23–2.17]), male sex (OR = 1.56 [1.19–2.04]), and positive family history of dementia (OR = 1.66 [1.19–2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02–1.10]) and APOE ɛ4 allele carriership (OR = 2.99 [1.81–4.94]). These results were similar across prescreen settings. Conclusions: Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity (the co-occurrence of multiple chronic conditions) is increasingly common, especially among people with dementia. Few neuroimaging studies have explored amyloid biomarkers in people with multimorbidity.Objective: We aimed to conduct the first study of the association between multimorbidity and cerebrospinal fluid amyloid-β42 (CSF Aβ).Method: The European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study V500.0 dataset includes volunteers aged ≥50 years from 12 sites. Participants undergo detailed phenotyping, including CSF measures and a self-reported medical history. Using logistic and linear regression analyses, we explored the association between multimorbidity and continuous chronic condition count with CSF Aβ positivity (Aβ42 <1000pg/ml) and continuous CSF Aβ concentration. All models were adjusted for age, sex, APOE status, education, and family history of dementia.Results: Among 447 eligible participants without dementia, the mean (SD) age was 66.6 (6.6) years, 234 (52.3%) were women, and 157 (35.1%) were amyloid positive. With chronic conditions regarded as pseudo-continuous, each additional condition carried a decreased likelihood of amyloid positivity (OR = 0.82, 95% CI: 0.68-0.97; p = 0.026). With CSF Aβ as a continuous variable, each additional condition was associated with an increase of 54.2 pg/ml (95% CI: 9.9-98.5, p = 0.017). Having ≥2 conditions was inversely associated with amyloid positivity (OR 0.59, 95% CI: 0.37-0.95, p = 0.030) compared to one or none.Conclusion: Our findings suggest that the established association between multimorbidity and dementia may be due to a pathway other than amyloid. However, this cross-sectional study does not allow us to make causal inferences. Longitudinal work is required to confirm the inverse association found. [ABSTRACT FROM AUTHOR]

Background: In a previous report, we used latent class analysis (LCA) to identify natural subgroups of older adults in the Einstein Aging Study (EAS) based on neuropsychological performance. These subgroups differed in demographics, genetic profile, and prognosis. Herein, we assess the generalizability of these findings to an independent sample, the Rush Memory and Aging Project (MAP), which used an overlapping, but distinct neuropsychological battery.Objective: Our aim was to identify the association of natural subgroups based on neuropsychological performance in the MAP cohort with incident dementia and compare them with the associations identified in the EAS.Methods: MAP is a community-dwelling cohort of older adults living in the northeastern Illinois, Chicago. Latent class models were applied to baseline scores of 10 neuropsychological measures across 1,662 dementia-free MAP participants. Results were compared to prior findings from the EAS.Results: LCA resulted in a 5-class model: Mixed-Domain Impairment (n = 71, 4.3%), Memory-specific-Impairment (n = 274, 16.5%), Average (n = 767, 46.1%), Frontal Impairment (n = 222, 13.4%), and a class of Superior Cognition (n = 328, 19.7%). Similar to the EAS, the Mixed-Domain Impairment, the Memory-Specific Impairment, and the Frontal Impairment classes had higher risk of incident Alzheimer's disease when compared to the Average class. By contrast, the Superior Cognition had a lower risk of Alzheimer's disease when compared to the Average class.Conclusions: Natural cognitive subgroups in MAP are similar to those identified in EAS. These similarities, despite study differences in geography, sampling strategy, and cognitive tests, suggest that LCA is capable of identifying classes that are not limited to a single sample or a set of cognitive tests. [ABSTRACT FROM AUTHOR]

Background: The oldest-old (aged ≥85 years) are the fastest growing age group, with the highest risk of cognitive impairment and dementia. This study investigated whether cognitive reserve applies to the oldest-old. This has implications for cognitive interventions in this age group.Methods: Baseline and 5-year follow-up data from the Newcastle 85+ Study were used (N = 845, mean age = 85.5, 38% male). A Cognitive Reserve Index (CRI) was created, including: education, social class, marital status, engagement in mental activities, social participation, and physical activity. Global (Mini-Mental State Examination) and domain specific (Cognitive Drug Research Battery subtests assessing memory, attention, and speed) cognitive functions were assessed. Dementia diagnosis was determined by health records. Logistic regression analysis examined the association between CRI scores and incident dementia. Mixed effects models investigated baseline and longitudinal associations between the CRI scores and cognitive function. Analyses controlled for sex, age, depression, and cardiovascular disease history.Results: Higher reserve associated with better cognitive performance on all baseline measures, but not 5-year rate of change. The CRI associated with prevalent, but not incident dementia.Conclusions: In the oldest-old, higher reserve associated with better baseline global and domain-specific cognitive function and reduced risk of prevalent dementia; but not cognitive decline or incident dementia. Increasing reserve could promote cognitive function in the oldest-old. The results suggest there would be little impact on trajectories, but replication is needed. Development of preventative strategies would benefit from identifying the role of each factor in building reserve and why rate of change is not affected. [ABSTRACT FROM AUTHOR]

Importance: Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated.Objective: To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia.Design, Setting, and Participants: Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors.Exposures: Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed.Outcomes: Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death.Results: There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (-2.8 points; 95% CI, -4.5 to -1.0; P < .001). Cognitive decline attributable to delirium was -0.37 MMSE points per year (95% CI, -0.60 to -0.13; P < .001). Decline attributable to the pathologic processes of dementia was -0.39 MMSE points per year (95% CI, -0.57 to -0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional -0.16 MMSE points per year (95% CI, -0.29 to -0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level-matched controls.Conclusions and Relevance: Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia. [ABSTRACT FROM AUTHOR]

Background: criteria for mild cognitive impairment (MCI) capture an intermediate cognitive state between normal ageing and dementia, associated with increased dementia risk. Whether criteria for MCI are applicable in the context of stroke and can be used to predict dementia in stroke cases is not known.Objectives: to determine the prevalence of MCI in individuals with stroke and identify predictors of 2-year incident dementia in stroke cases.Methods: individuals were from the Medical Research Council Cognitive Function and Ageing Study. MCI prevalence in individuals with stroke was determined. Logistic regression, with receiver operating characteristic curve analysis, was used to identify variables associated with risk of dementia in stroke cases including MCI criteria, demographic, health and lifestyle variables.Findings: of 2,640 individuals seen at the first assessment, 199 reported stroke with no dementia. In individuals with stroke, criteria for MCI are not appropriate, with less than 1% of stroke cases being classified as having MCI. However, in individuals with stroke two components of the MCI definition, subjective memory complaint and cognitive function (memory and praxis scores) predicted 2-year incident dementia (area under the curve = 0.85, 95% CI: 0.77–0.94, n = 113).Conclusion: criteria for MCI do not appear to capture risk of dementia in the context of stroke in the population. In stroke cases, subjective and objective cognitive performance predicts dementia and these variables could possibly be incorporated into dementia risk models for stroke cases. Identifying individuals with stroke at greatest risk of dementia has important implications for treatment and intervention. [ABSTRACT FROM PUBLISHER]

Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia. However, previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline. Herein, we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline. We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium. The Vantaa 85+ study examined 553 individuals (92% of those eligible) aged &geq;85 years at baseline, 3, 5, 8 and 10 years. Brain autopsy was performed in 52%. Fixed and random-effects regression models were used to assess associations between (i) delirium and incident dementia and (ii) decline in Mini-Mental State Examination scores in the whole group. The relationship between dementia and common neuropathological markers (Alzheimer-type, infarcts and Lewy-body) was modelled, stratified by history of delirium. Delirium increased the risk of incident dementia (odds ratio 8.7, 95% confidence interval 2.1–35). Delirium was also associated with worsening dementia severity (odds ratio 3.1, 95% confidence interval 1.5–6.3) as well as deterioration in global function score (odds ratio 2.8, 95% confidence interval 1.4–5.5). In the whole study population, delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year (95% confidence interval 0.11–1.89) than those with no history of delirium. In individuals with dementia and no history of delirium (n = 232), all pathologies were significantly associated with dementia. However, in individuals with delirium and dementia (n = 58), no relationship between dementia and these markers was found. For example, higher Braak stage was associated with dementia when no history of delirium (odds ratio 2.0, 95% confidence interval 1.1–3.5, P = 0.02), but in those with a history of delirium, there was no significant relationship (odds ratio 1.2, 95% confidence interval 0.2–6.7, P = 0.85). This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid, apolipoprotein &varepsilon; status, presence of infarcts, α-synucleinopathy and neuronal loss in substantia nigra. These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old. However, in this study, the relationship did not appear to be mediated by classical neuropathologies associated with dementia. [ABSTRACT FROM AUTHOR]

The article discusses a study on the relationship between Vitamin D and cognitive decline or dementia using subjects from Italy. Adults 65 years or older were interviewed, underwent cognitive assessments and medical examinations and provided blood samples for the study. It was found that low levels of vitamin D were linked with substantial cognitive decline in older people during the period of study.

Background: Delirium is a heterogeneous syndrome with inattention as the core feature. There is considerable variation in the presence and degree of other symptom domains such as altered arousal, psychotic features and global cognitive dysfunction. Delirium is independently associated with increased mortality, but it is unclear whether individual symptom domains of delirium have prognostic importance. We conducted a systematic review and meta-analysis of studies in hospitalised adults in general settings to identify the relationship between symptom domains of delirium and outcomes. (PROSPERO: CRD42018093935).Methods: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, clinicaltrials.gov and the Cochrane Central Register of Controlled Trials from inception to November 2019. We included studies of hospitalised adults that reported associations between symptom domains of delirium and 30-day mortality (primary outcome), and other outcomes including mortality at other time points, length of stay, and dementia. Reviewer pairs independently screened articles, extracted data, and assessed risk of bias (Risk of Bias Assessment tool for Non-randomized Studies) and quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. We performed random-effects meta-analyses stratified by delirium domain where possible.Results: From 7092 citations we included 6 studies (6002 patients, 1112 with delirium). Higher mortality (ranging from in-hospital to follow-up beyond 12 months) was associated with altered arousal (pooled Odds Ratio (OR) 2.80, 95% Confidence Interval (CI) 2.33-3.37; moderate-quality evidence), inattention (pooled OR 2.57, 95% CI 1.74-3.80; low-quality evidence), and in single studies with disorientation, memory deficits and disorganised thoughts. Risk of bias varied across studies but was moderate-to-high overall, mainly due to selection bias, lack of blinding of assessments and unclear risk of selective outcome reporting. We found no studies on the association between psychotic features, visuospatial deficits or affective disturbances in delirium and outcomes, or studies reporting non-mortality outcomes.Conclusions: Few studies have related symptom domains of delirium to outcomes, but the available evidence suggests that altered arousal and inattention in delirium are associated with higher mortality than normal arousal and attention in people with or without delirium. Measurable symptom domains of delirium may have value in predicting survival and stratifying patients for treatment. We recommend that future delirium studies report outcomes by symptom domain. [ABSTRACT FROM AUTHOR]