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Introduction: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field., Methods: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations., Results: Overall, the recommendations support the delivery of decentralized trials in dementia prevention provided adequate safety checks and balances are included. A total of 40 recommendations are presented, spanning aspects of decentralized clinical trials, including safety, dispensing, outcome assessment, and data collection., Discussion: These recommendations provide an accessible, pragmatic guide for the design and conduct of remote medication trials for dementia prevention., Highlights: Clinical trials of medication have begun adopting decentralized approaches. Researchers in the field lack guidance on what would be appropriate circumstances and frameworks for what would be appropriate circumstances and frameworks for the use of decentralized trial methods in dementia prevention. The present report provides consensus-based expert recommendations for decentralized clinical trials for dementia prevention., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Home- and community-based services (HCBS) users, on average, experience hospitalizations more frequently than nursing facility residents. However, little is known about state-level variation in such adverse events among these groups. Using 2018 Medicare and Medicaid claims for dual-eligible beneficiaries with Alzheimer's disease and related dementias, we described hospitalization and emergency department (ED) visit rates among HCBS users and nursing facility residents and observed substantial state-level variation. In addition, consistent with prior evidence, we found more frequent hospitalizations and ED visits among HCBS users than nursing facility residents. The magnitude of this difference varied considerably across states, and the degree of variation was greatest among beneficiaries with six or more comorbid conditions. Our findings represent a crucial initial exploration of the state-level variation in adverse events among HCBS users and nursing facility residents, paving the way for further investigations into factors that contribute to this variability., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Social isolation is a risk factor for cognitive decline and dementia. We conducted a randomized controlled clinical trial (RCT) of enhanced social interactions, hypothesizing that conversational interactions can stimulate brain functions among socially isolated older adults without dementia. We report topline results of this multisite RCT (Internet-based conversational engagement clinical trial [I-CONECT]; NCT02871921)., Research Design and Methods: The experimental group received cognitively stimulating semistructured conversations with trained interviewers via internet/webcam 4 times per week for 6 months (induction) and twice per week for an additional 6 months (maintenance). The experimental and control groups both received weekly 10 minutes telephone check-ins. Protocol modifications were required due to the coronavirus disease 2019 pandemic., Results: A total of 186 participants were randomized. After the induction period, the experimental group had higher global cognitive test scores (Montreal Cognitive Assessment [primary outcome]; 1.75 points [p = .03]) compared with the control group. After induction, experimental group participants with normal cognition had higher language-based executive function (semantic fluency test [secondary outcome]; 2.56 points [p = .03]). At the end of the maintenance period, the experimental group of mild cognitive impairment subjects had higher encoding function (Craft Story immediate recall test [secondary outcome]; 2.19 points [p = .04]). Measure of emotional well-being improved in both control and experimental groups. Resting-state functional magnetic resonance imaging showed that the experimental group had increased connectivity within the dorsal attention network relative to the control group (p = .02), but the sample size was limited., Discussion and Implications: Providing frequent stimulating conversational interactions via the internet could be an effective home-based dementia risk-reduction strategy against social isolation and cognitive decline., Clinical Trials Registration Number: NCT02871921., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

There is an urgent need for interventions that can prevent or delay cognitive decline and dementia. Decades of epidemiological research have identified potential pharmacological strategies for risk factor modification to prevent these serious conditions, but clinical trials have failed to confirm the potential efficacy for such interventions. Our multidisciplinary international group reviewed seven high-potential intervention strategies in an attempt to identify potential reasons for the mismatch between the observational and trial results. In considering our findings, we offer constructive recommendations for the next steps. Overall, we observed some differences in the observational evidence base for the seven strategies, but several common methodological themes that emerged. These themes included the appropriateness of trial populations and intervention strategies, including the timing of interventions and other aspects of trials methodology. To inform the design of future clinical trials, we provide recommendations for the next steps in finding strategies for effective dementia risk reduction., (© 2021 the Alzheimer's Association.)

Introduction: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results., Methods: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System., Results: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols., Discussion: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

In the past decade a large body of evidence has accumulated on risk factors for dementia, primarily from Europe and North America. Drawing on recent integrative reviews and a consensus workshop, the International Research Network on Dementia Prevention developed a consensus statement on priorities for future research. Significant gaps in geographical location, representativeness, diversity, duration, mechanisms, and research on combinations of risk factors were identified. Future research to inform dementia risk reduction should fill gaps in the evidence base, take a life-course, multi-domain approach, and inform population health approaches that improve the brain-health of whole communities.

Background: Incidence rates of dementia appear to be declining in high-income countries according to several large epidemiological studies. We aimed to describe declining incident dementia rates across successive birth cohorts in a U.S. population-based sample and to explore the influences of sex and education on these trends., Methods: We pooled data from two community-sampled prospective cohort studies with similar study aims and contiguous sampling regions: the Monongahela Valley Independent Elders Survey (1987-2001) and the Monongahela-Youghiogheny Healthy Aging Team (2006-Ongoing). We identified four decade-long birth cohorts spanning birth years 1902-1941. In an analysis sample of 3,010 participants (61% women, mean baseline age = 75.7 years, mean follow-up = 7.1 years), we identified 257 cases of incident dementia indicated by a Clinical Dementia Rating of 1.0 or higher. We used Poisson regression to model incident dementia rates by birth cohort, age, sex, education, and interactions of Sex × Cohort and Sex × Education. We further examined whether cohort effects varied by education, testing a Cohort × Education interaction and stratifying the models by education., Results: Compared to the earliest birth cohort (1902-1911), each subsequent cohort had a significantly lower incident dementia rate (1912-1921: incidence rate ratio [IRR] = 0.655, 95% confidence interval [95% CI] = 0.477-0.899; 1922-1931: IRR = 0.387, 95% CI = 0.265-0.564; 1932-1941: IRR = 0.233, 95% CI = 0.121-0.449). We observed no significant interactions of either sex or education with birth cohort., Conclusions: A decline in incident dementia rates was observed across successive birth cohorts independent of sex, education, and age., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cortical gray matter (GM) and white matter (WM) deterioration are signals of neurodegeneration and increased dementia risk; however, their specific etiologies in dementia-free aging is unclear., Objective: The objective of this study was to examine potentially modifiable risk factors of GM and WM degeneration in a well-characterized cohort of dementia-free elderly., Methods: 96 Okinawan elderly participants (age 83.6) from the Keys to Optimal Cognitive Aging Project (KOCOA) underwent MRI and cognitive evaluation. Serum markers of inflammation (interleukin-6 (IL-6), high sensitivity C-reactive protein), cerebrovascular disease (systolic blood pressure (SBP) 140+, hemoglobin A1C (HgbA1C), total cholesterol), and essential minerals (copper (Cu), magnesium, and calcium) were examined in relation to mean cortical thickness (MCT) and white matter hyperintensities (WMH), adjusting for age and gender. Voxel-based morphometry (VBM) analyses identified relationships between regional GM density and the above markers., Results: Decreased MCT was associated with SBP 140 + (p = 0.029) and increased serum IL-6 (p = 0.036), HgbA1C (p = 0.002), and Cu (p = 0.025). In VBM analyses, increased IL-6, HgbA1C, and Cu were associated with decreased GM density in temporal lobe regions. HgbA1C (p = 0.004) was associated with greater WMH volume., Conclusions: Peripheral markers of Cu, CVD risk, and inflammation are associated with MRI-markers of decreased brain health in dementia-free Okinawan elderly, with regional cortical thinning in areas involved in early accumulation of Alzheimer's disease pathology. Results identify potentially modifiable biomarkers as targets in the prevention of dementia in older individuals.

Objective: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI)., Methods: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States., Results: Mean follow-up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical diagnosis of MCI. In terms of non-AD pathologies, both primary age-related tauopathy (p < 0.05) and brain arteriolosclerosis pathology (p < 0.001) were more severe in MCI than cognitively intact controls. Among the group that remained MCI until death, mixed AD neuropathologic changes (ADNC; ≥1 comorbid pathology) were more frequent than "pure" ADNC pathology (55% vs 22%); suspected non-Alzheimer pathology comprised the remaining 22% of cases. A majority (74%) of subjects who died with MCI were without "high"-level ADNC, Lewy body disease, or hippocampal sclerosis pathologies; this group was enriched in cerebrovascular pathologies. Subjects who died with dementia and were without severe neurodegenerative pathologies tended to have cerebrovascular pathology and carry the MCI diagnosis for a longer interval., Interpretation: MCI diagnosis usually was associated with comorbid neuropathologies; less than one-quarter of MCI cases showed "pure" AD at autopsy. Ann Neurol 2017;81:549-559., (© 2017 American Neurological Association.)

Background: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders., Methods/design: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress., Discussion: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.

Importance: While brain volume changes are used as surrogate markers for Alzheimer disease neuropathology in clinical studies, the extent to which these changes are due to pathologic features of Alzheimer disease in the aging brain is not well established. This study aims to clarify the neuropathologic correlates of longitudinal brain atrophy., Objective: To examine the association between brain atrophy during life and neuropathology in an elderly population., Design: Autopsy study of a cohort of elderly individuals., Setting: Community-based population., Participants: Seventy-one healthy elderly individuals were selected from participants of the Oregon Brain Aging Study for having an autopsy, more than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging scan within 36 months of death., Main Outcomes and Measures: The associations between brain volume trajectories (ventricular, total brain, and hippocampal) and time interaction terms for neurofibrillary tangles, neuritic plaques, gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ε4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or dementia as time-varying covariates) were examined in mixed-effects models, adjusting for duration of follow-up and age at death., Results: Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ε4 allele presence, and dementia diagnosis. Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy., Conclusions and Relevance: Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (mild cognitive impairment and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment.

Objective: To track cognitive change over time in dementia-free older adults and to examine terminal cognitive decline., Methods: A total of 1,230 subjects who remained free from dementia over 14 years of follow-up were included in a population-based epidemiologic cohort study. First, we compared survivors and decedents on their trajectories of 5 cognitive functions (learning, memory, language, psychomotor speed, executive functions), dissociating practice effects which can mask clinically significant decline from age-associated cognitive decline. We used longitudinal mixed-effects models with penalized linear spline. Second, limiting the sample to 613 subjects who died during follow-up, we identified the inflection points at which the rate of cognitive decline accelerated, in relation to time of death, controlling for practice effects. We used mixed-effects model with a change point., Results: Age-associated cognitive trajectories were similar between decedents and survivors without dementia. However, substantial differences were observed between the trajectories of practice effects of survivors and decedents, resembling those usually observed between normal and mildly cognitively impaired elderly. Executive and language functions showed the earliest terminal declines, more than 9 years prior to death, independent of practice effects., Conclusions: Terminal cognitive decline in older adults without dementia may reflect presymptomatic disease which does not cross the clinical threshold during life. Alternatively, cognitive decline attributed to normal aging may itself represent underlying neurodegenerative or vascular pathology. Although we cannot conclude definitively from this study, the separation of practice effects from age-associated decline could help identify preclinical dementia.

Background: The Mini-mental State Examination (MMSE) is widely used in Japan and the U.S.A. for cognitive screening in the clinical setting and in epidemiological studies. A previous Japanese community study reported distributions of the MMSE total score very similar to that of the U.S.A., Methods: Data were obtained from the Monongahela Valley Independent Elder's Study (MoVIES), a representative sample of community-dwelling elderly people aged 65 and older living near Pittsburgh, U.S.A., and from the Tajiri Project, with similar aims in Tajiri, Japan. We examined item-by-item distributions of the MMSE between two cohorts, comparing (1) percentage of correct answers for each item within each cohort, and (2) relative difficulty of each item measured by Item Characteristic Curve analysis (ICC), which estimates log odds of obtaining a correct answer adjusted for the remaining MMSE items, demographic variables (age, gender, education) and interactions of demographic variables and cohort., Results: Median MMSE scores were very similar between the two samples within the same education groups. However, the relative difficulty of each item differed substantially between the two cohorts. Specifically, recall and auditory comprehension were easier for the Tajiri group, but reading comprehension and sentence construction were easier for the MoVIES group., Conclusions: Our results reaffirm the importance of validation and examination of thresholds in each cohort to be studied when a common instrument is used as a dementia screening tool or for defining cognitive impairment.

Objective: The objective of this study was to examine associations between discrepancies in health information provided to primary care providers and severity of impairment in older patients with and without dementia., Methods: This study included brief assessment and medical record review of 1,107 patients with a mean (standard deviation) age of 76.3 (6.6) years (range: 65-100 years) in seven small-town primary care practices. In 358 patients, detailed in-home assessment included demographics; dementia by Clinical Dementia Rating (CDR) scale; and frequencies of memory complaints, falls, and inadvertent medication nonadherence determined from medical records and standardized in-home research assessments. Main outcome variables were trends in discrepancies between chart reviews and research assessments. Main explanatory variable was CDR box total scores., Results: Proportions of patients reporting memory complaints and falls, and evidence of inadvertent nonadherence, in the charts and by research assessment increased with CDR. Discrepancies between medical record and research assessment, were also associated with CDR, showing linear trends for memory complaints and inadvertent nonadherence and a quadratic trend for falls., Conclusion: Memory complaints, falls, and inadvertent medication nonadherence increase with dementia severity. The levels of discrepancy between information patients provided to their physicians and information they provided in response to detailed, standardized assessments, also varied with dementia severity. Physicians should be alert to the possibility of receiving unreliable health information from even mildly demented patients, whether or not dementia has been detected.

Objectives: To identify characteristics of older primary care patients who were cognitively impaired and who underwent mental status testing by their physicians., Design: Cross-sectional and retrospective analysis., Setting: Seven small-town primary care practices., Participants: A total of 1,107 patients with a mean+/-standard deviation age of 76.3+/-6.6, screened using the Mini-Mental State Examination (MMSE); medical records reviewed., Measurements: Demographics, MMSE, medical record information. Odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, sex, and education., Results: Thirty-one percent of the sample had MMSE scores of less than 25. Among these patients, physicians documented memory loss in only 23% which was significantly more often than in the higher scoring group (OR=1.9, 95% CI=1.3-2.8), basic activity of daily living (ADL) impairment in 7.9% (OR=2.4, 95% CI=1.3-4.4), instrumental ADL (IADL) impairment in 6.7% (OR=2.2, 95% CI=1.1=4.2), dementia in 12.2% (OR=3.7, 95% CI=2.0-6.8), and prescription of cholinesterase inhibitors in 7.6% (OR=4.4, 95% CI=1.9-10.2). Physicians recorded mental status testing largely in patients with research MMSE scores of 24 to 28, significantly more often when they also documented memory loss (OR=3.8, 95% CI=2.5-5.6) or impaired IADLs (OR=2.7, 95% CI=1.4-5.2), diagnosed dementia (OR=4.9, 95% CI=2.8-8.6), referred to specialists (OR=6.3, 95% CI=2.5-16.2) or social services (OR=3.6, 95% CI=1.8-7.3), or prescribed cholinesterase inhibitors (OR=8.5, 95% CI=4.2-17.5)., Conclusion: Physicians noted impairment in a minority of impaired patients. They tested mental status in those with documented cognitive and functional difficulties, in very mildly impaired patients, and in those for whom they intervened.

Objectives: To compare the use of lipid-lowering drugs in community-dwelling older adults with and without dementia., Design: Comparison of lipid-lowering drug use by demented cases and nondemented controls based on secondary analysis of data from a longitudinal epidemiologic study., Setting: Longitudinal study of a largely rural, low- socioeconomic-status, community-based cohort of older persons residing in the mid-Monongahela Valley of South-west Pennsylvania (the Monongahela Valley Independent Elders Survey)., Participants: Eight hundred forty-five individuals of mean +/- standard deviation (SD) age of 80.5 +/- 4.6, participating in the fifth biennial wave of data collection., Measurements: Demographics; medical history; medication regimen (including examination of prescription bottle labels); self-report of most recent visit to primary care physician (PCP); and standardized clinical assessment to determine presence of dementia, including Clinical Dementia Rating (CDR)., Results: One hundred seventy participants (20.1% of total subject cohort) had dementia, with a CDR of 0.5 or greater. Mean ages of demented and nondemented individuals were 83.5 +/- 5.1 and 79.8 +/- 4.2, respectively. Similar proportions, 87.7% and 89.5%, of these groups reported PCP visits in the previous year. Of the total sample, 9.4% (3.5% of the demented and 10.8% of the nondemented) were taking lipid-lowering drugs. After adjustment for age, sex, education, visit with PCP within the past year, and potential confounding clinical and lifestyle variables (self-reported heart disease, stroke or transient ischemic attacks, hypertension, smoking, and alcohol consumption), dementia was associated with a lower likelihood of taking a lipid-lowering drug (odds ratio = 0.39, 95% confidence interval = 0.16-0.95). In post hoc subgroup analyses, similar results were found when restricting lipid-lowering drugs to statins alone but were not statistically significant. Drug use was not associated with severity of dementia (CDR = 0.5 vs CDR >or= 1)., Conclusions: Demented individuals were less likely than their nondemented counterparts to be taking lipid-lowering drugs. This finding could reflect different prescribing patterns by physicians for demented and nondemented patients or a possible protective effect of these drugs against dementia.

There is a shortage of adequate screening instruments for dementia in poorly educated populations and non-English-speaking groups. An epidemiological survey was conducted in a population-based, largely illiterate, sample of 5,126 individuals aged 55 and older in 28 villages in the rural community of Ballabgarh in northern India. All participants were administered a general mental status test, the Hindi Mental State Examination (HMSE), and a brief battery of neuropsychological tests. Their informants answered a questionnaire assessing functional ability, the Everyday Abilities Scale for India (EASI). Six hundred thirty-two participants underwent clinical diagnostic evaluation for dementia. We investigated whether the sensitivity, specificity, and predictive value for dementia of the mental status test could be improved by the addition of the brief neuropsychological test battery or the functional questionnaire, comparing the instruments alone and in combination. In participants who could be tested cognitively, the HMSE, the neuropsychological battery, and EASI had sensitivities of 81.3%, 81.3%, and 62.5%, respectively, with specificities of 60.2%, 74.5%, and 89.7%, respectively. The combination of all three was 93.8% sensitive and 41.8% specific. The sensitivity of the HMSE alone was nonsignificantly improved by the addition of either the EASI or the neuropsychological battery, whereas its specificity was significantly decreased by either addition. An advantage of the EASI was that it could also be administered to informants of subjects who were cognitively untestable. In this largely illiterate community, with a low prevalence of dementia, the combination of cognitive tests and a functional ability questionnaire had substantial value for population screening.

Purpose: We examined differential effects of cognitive impairment on each of the activities of daily living (ADL) and instrumental activities of daily living (IADL) tasks. Design and Methods: In a 3-year follow-up of community-dwelling elderly persons in Azuchi, Japan, we assessed cognition by using the Hasegawa Dementia Scale. We examined (a) the cross-sectional association between cognitive impairment and functional disability in each ADL-IADL item; (b) cognitive impairment as a risk factor for incident disability in each ADL-IADL item, through logistic regression models; and (c) probabilities of incident loss of ADL-IADL abilities or death in 3 years, using multinomial logistic regression models. We also calculated the population attributable risk (PAR%) of cognitive impairment on incident loss of task-specific ADL-IADL abilities. Results: Cross-sectionally, the severity of cognitive impairment was associated with disability in each ADL-IADL task, with larger effects shown for ADL items. Longitudinally, minimally or mildly cognitively impaired individuals had a significantly higher risk of losing functional abilities compared with those with intact cognition. The PAR% indicated that cognitive impairment accounts for 11% to 36% of incident disability in ADL-IADL tasks, with the highest PAR% shown for the ability to feed oneself. Implications: Cognitively impaired subjects are heterogeneous; the severity of cognitive impairment has a different impact on incident loss of task-specific ADL-IADL abilities, and comorbidities could affect disabilities differently. Consideration of these heterogeneities will enrich future studies on the impact of cognitive impairment on ADL-IADL abilities.Key Words: Hasegawa Dementia Scale, ADL, IADL, Population attributable risk, Caregiving needs

BackgroundConsensus guidance for the development and identification of high-quality Alzheimer's disease clinical trials is needed for protocol development and conduct of clinical trials.MethodsAn ad hoc consensus committee was convened in conjunction with the Alzheimer's Association to develop consensus recommendations.ResultsConsensus was readily reached for the need to provide scientific justification, registration of trials, institutional review board oversight, conflict of interest disclosure, funding source disclosure, defined trial population, recruitment resources, definition of the intervention, specification of trial duration, appropriate payment for participant engagement, risk-benefit disclosure as part of the consent process, and the requirement to disseminate and/or publish trial results even if the study is negative.ConclusionsThis consensus guidance should prove useful for the protocol development and conduct of clinical trials, and may further provide a platform for the development of education materials that may help guide appropriate clinical trial participation decisions for potential trial participants and the general public.

BackgroundConsensus guidance for the development and identification of high-quality Alzheimer's disease clinical trials is needed for protocol development and conduct of clinical trials.MethodsAn ad hoc consensus committee was convened in conjunction with the Alzheimer's Association to develop consensus recommendations.ResultsConsensus was readily reached for the need to provide scientific justification, registration of trials, institutional review board oversight, conflict of interest disclosure, funding source disclosure, defined trial population, recruitment resources, definition of the intervention, specification of trial duration, appropriate payment for participant engagement, risk-benefit disclosure as part of the consent process, and the requirement to disseminate and/or publish trial results even if the study is negative.ConclusionsThis consensus guidance should prove useful for the protocol development and conduct of clinical trials, and may further provide a platform for the development of education materials that may help guide appropriate clinical trial participation decisions for potential trial participants and the general public.

IntroductionFederally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.5, and 1.MethodsFirst, we matched participants receiving V2 tests (V2 cohort) and V3 tests (V3 cohort) in their cognitive functions using tests common to both versions. Then, we compared receiver-operating characteristic (ROC) area under the curve in differentiating CDRs for the remaining tests.ResultsSome V3 tests performed better than V2 tests in differentiating between CDR 0.5 and 0, but the improvement was limited to Caucasian participants.DiscussionFurther efforts to improve the ability for early identification of cognitive decline among diverse racial groups are required.

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

Biological and clinical heterogeneity is a major challenge in research for developing new treatments for Alzheimer's disease (AD). AD may be defined by its amyloid beta and tau pathologies, but we recognize that mixed pathologies are common, and that diverse genetics, central nervous system (CNS) and systemic pathophysiological processes, and environmental/experiential factors contribute to AD's diverse clinical and neuropathological features. All these factors are rational targets for therapeutic development; indeed, there are hundreds of candidate pharmacological, dietary, neurostimulation, and lifestyle interventions that show benefits in homogeneous laboratory models. Conventional clinical trial designs accommodate heterogeneity poorly, and this may be one reason that progress in translating candidate interventions has been so difficult. We review the challenges of AD's heterogeneity for the clinical trials enterprise. We then discuss how advances in repeatable biomarkers and digital phenotyping enable novel "single‐case" and adaptive trial designs to accelerate therapeutics development, moving us closer to personalized research and medicine for AD. Highlights: Alzheimer's disease is diverse in its clinical features, course, risks, and biology.Typical randomized controlled trials are exclusive and necessarily large to attain arm comparability with broad outcomes.Repeated blood biomarkers and digital tracking can improve outcome measure precision and sensitivity.This enables the use of novel "single‐case" and adaptive trial designs for inclusivity, rigor, and efficiency. [ABSTRACT FROM AUTHOR]

IntroductionThe neuropsychological battery of the Uniform Data Set (UDSNB) was implemented in 2005 by the National Institute on Aging (NIA) Alzheimer Disease Centers program to measure cognitive performance in dementia and mild cognitive impairment due to Alzheimer Disease. This paper describes a revision, the UDSNB 3.0.MethodsThe Neuropsychology Work Group of the NIA Clinical Task Force recommended revisions through a process of due diligence to address shortcomings of the original battery. The UDSNB 3.0 covers episodic memory, processing speed, executive function, language, and constructional ability. Data from 3602 cognitively normal participants in the National Alzheimer Coordinating Center database were analyzed.ResultsDescriptive statistics are presented. Multivariable linear regression analyses demonstrated score differences by age, sex, and education and were also used to create a normative calculator available online.DiscussionThe UDSNB 3.0 neuropsychological battery provides a valuable non proprietary resource for conducting research on cognitive aging and dementia.

IntroductionRacial and ethnic groups are under-represented among research subjects who assent to brain donation in Alzheimer disease research studies. There has been little research on this important topic. Although there are some studies that have investigated the barriers to brain donation among African American study volunteers, there is no known research on the factors that influence whether or not Asians or Latinos are willing to donate their brains for research.MethodsAfrican American, Caucasian, Asian, and Latino research volunteers were surveyed at 15 Alzheimer Disease Centers to identify predictors of willingness to assent to brain donation.ResultsPositive predictors included older age, Latino ethnicity, understanding of how the brain is used by researchers, and understanding of what participants need to do to ensure that their brain will be donated. Negative predictors included African/African American race, belief that the body should remain whole at burial, and concern that researchers might not be respectful of the body during autopsy.DiscussionThe predictive factors identified in this study may be useful for researchers seeking to increase participation of diverse ethnic groups in brain donation.

Introduction: Emotional functioning in older adults is influenced by normal aging and cognitive impairment, likely heterogeneous across positive versus negative aspects of emotional functioning. Little is known about positive emotional experiences at the early stages of cognitive impairment. Methods: We assessed different aspects of emotional functioning among 448 participants aged 65+ (Normal Control (NC) = 276, Mild Cognitive Impairment (MCI) = 103, and mild dementia of the Alzheimer type (mild DAT) = 69) and tested moderators. Results: Compared to NC, older adults with MCI and mild DAT have maintained many positive aspects of emotional functioning, despite higher levels of negative affect, sadness, and loneliness. Among the oldest-old, the mild DAT group experienced higher fear and lower self-efficacy. Discussion: Older adults at early stages of cognitive impairment can experience positive aspects of emotional functioning, such as positive affect, purpose, and life satisfaction, all of which are important buildable psychological resources for coping. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We developed demographically‐adjusted normative data for Spanish‐ and English‐speaking Latinos on the Version 3.0 of the National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS3‐NB). METHODS: Healthy Latino adults (N = 437) age 50–94 (191 Spanish‐ and 246 English‐speaking) enrolled in Alzheimer's Disease Research Centers completed the UDS3‐NB in their preferred language. Normative data were developed via multiple linear regression models on UDS3‐NB raw scores stratified by language group with terms for demographic characteristics (age, years of formal education, and sex). RESULTS: Younger age and more years of education were associated with better performance on most tests in both language groups, with education being particularly influential on raw scores among Spanish‐speakers. Sex effects varied across tests and language groups. DISCUSSION: These normative data are a crucial step toward improving diagnostic accuracy of the UDS3‐NB for neurocognitive disorders among Latinos in the United States and addressing disparities in Alzheimer's disease and related dementias. Highlights: We developed normative data on the UDS3‐NB for Latinos in the US ages 50–94.Younger age and more years of education were linked to better raw scores in several cognitive tests.Education was particularly influential on raw scores among Spanish‐speakers.Sex effects varied across tests and between English‐ and Spanish‐speaking Latinos.These normative data might improve diagnostic accuracy of the UDS3‐NB among Latinos. [ABSTRACT FROM AUTHOR]

Background: To respect people's preference for aging in place and control costs, many state Medicaid programs have enacted policies to expand home and community‐based services as an alternative to nursing facility care. However, little is known about the use of Medicaid long‐term services and supports (LTSS) at a national level, particularly among dual‐eligible beneficiaries with Alzheimer's disease and related dementias (ADRD). Methods: Using Medicare and Medicaid claims of 30 states from 2016, we focused on dual‐eligible beneficiaries 65 years or older with ADRD and described their use of any form of LTSS and sub‐types of LTSS (home‐based, community‐based, and nursing facility services) across states. Results: We found that 80.5% of dual‐eligible beneficiaries with ADRD received some form of Medicaid LTSS in 2016. The most common LTSS setting was nursing facility (46.7%), followed by home (31.5%) and community (12.2%). There was sizeable state variation in the percentage of dual‐eligible beneficiaries with ADRD who used any form of LTSS (ranging from 61% in Maine to 96% in Montana). The type of LTSS used also varied widely across states. For example, home‐based service use ranged from 9% in Maine, Arizona, and South Dakota to 62% in Oregon. Nursing facility services were the most common type of LTSS in most states. However, home‐based service use exceeded nursing facility use in Oregon, Alaska, and California. Conclusions: Our findings suggest substantially different use of LTSS across states among dual‐eligible beneficiaries with ADRD. Given the importance of LTSS for this population and their families, a deeper understanding of state LTSS policies and other factors that contribute to wide state variation in LTSS use will be necessary to improve access to LTSS across states. [ABSTRACT FROM AUTHOR]

Introduction: Early detection of cognitive decline in older adults is a public health priority. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA), a multisite study, is validating cognition, emotion, motor, and sensory modules of the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in the aging spectrum from cognitively normal to dementia of the Alzheimer's type (DAT). Methods: Participants 65 to 85 years old, in demographic groups racially proportional to the general US population, are recruited in one of three groups to validate the NIHTB: cognitively normal, amnestic mild cognitive impairment (aMCI), or mild DAT. Additional special emphasis cohorts include (1) Blacks in the three clinical groups; (2) Spanish‐speakers in the three clinical groups; (3) cognitively normal, population‐proportional, over age 85. Discussion: Longitudinal study will determine whether NIHTB can predict cognitive decline and is associated with Alzheimer's disease biomarkers. Here, we detail the methods for the ARMADA study. [ABSTRACT FROM AUTHOR]

There is an urgent need for interventions that can prevent or delay cognitive decline and dementia. Decades of epidemiological research have identified potential pharmacological strategies for risk factor modification to prevent these serious conditions, but clinical trials have failed to confirm the potential efficacy for such interventions. Our multidisciplinary international group reviewed seven high‐potential intervention strategies in an attempt to identify potential reasons for the mismatch between the observational and trial results. In considering our findings, we offer constructive recommendations for the next steps. Overall, we observed some differences in the observational evidence base for the seven strategies, but several common methodological themes that emerged. These themes included the appropriateness of trial populations and intervention strategies, including the timing of interventions and other aspects of trials methodology. To inform the design of future clinical trials, we provide recommendations for the next steps in finding strategies for effective dementia risk reduction. [ABSTRACT FROM AUTHOR]

Aims: We aim to establish the feasibility and acceptability of the Tele‐STELLA (Support via Telehealth: Living and Learning with Advancing Alzheimer's Disease and Related Dementias) intervention. We will also assess the efficacy of the intervention in reducing the frequency of behavioural symptoms of dementia as well as family Care Partner reactivity to the symptoms. Design: This is a multi‐component, quasi‐experimental study that focuses on facilitating effective management of behavioural symptoms that occur in the later stages of dementia. Methods: Family Care Partners (n = 124) for persons with Alzheimer's disease will participate in two 8‐week videoconferencing components that address behavioural symptoms—in both the persons with Alzheimer's disease and their Care Partners. In the first component ('Nova'), Care Partners work with one nurse for an hour/week for 4 weeks, then they join a small group for another 4 weeks. In the second component ('Constellation'), Care Partners work in a larger group to hone skills and knit supportive relationships. Behavioural symptom frequency and Care Partner reactivity to the behaviours will be measured prior to, during and after the intervention. The study is funded by the United States National Institute on Aging (R01AG067546); funding was initiated as on February, 2021. Discussion: Tele‐STELLA fills a gap in current videoconference‐based psychoeducational interventions in that it offers real‐time interaction with nurses and peers. The intervention was designed with feedback by pilot participants. This study will assess Tele‐STELLA in its current, novel format; thus, preparing it for a larger, future randomized controlled trial. Impact: Tele‐STELLA addresses symptoms that occur in the later stages of dementia, providing families with tools to facilitate effective behavioural management. Because Tele‐STELLA is implemented via videoconferencing, it targets Care Partners who face barriers to support, such as cost and transportation. Trial Registration: This trial is registered with ClinicalTrials.gov (#NCT04627662). [ABSTRACT FROM AUTHOR]

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega‐3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non‐steroidal anti‐inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti‐hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data. [ABSTRACT FROM AUTHOR]

The search for early biomarkers of mild cognitive impairment (MCI) has been central to the Alzheimer's Disease (AD) and dementia research community in recent years. To identify MCI status at the earliest possible point, recent studies have shown that linguistic markers such as word choice, utterance and sentence structures can potentially serve as preclinical behavioral markers. Here we present an adaptive dialogue algorithm (an AI-enabled dialogue agent) to identify sequences of questions (a dialogue policy) that distinguish MCI from normal (NL) cognitive status. Our AI agent adapts its questioning strategy based on the user's previous responses to reach an individualized conversational strategy per user. Because the AI agent is adaptive and scales favorably with additional data, our method provides a potential avenue for large-scale preclinical screening of neurocognitive decline as a new digital biomarker, as well as longitudinal tracking of aging patterns in the outpatient setting. [ABSTRACT FROM AUTHOR]

Background: While being obese in mid-life is associated with an increased risk of dementia and cognitive decline in late-life, being obese in late-life is shown to be associated with a lower risk of these outcomes in some studies. This phenomenon is known as the "obesity paradox", but the underlying reasons and potential sex difference have not been well understood.Objective: To investigate the association between cognition and waist circumference (WC), an alternative measure of body fat which can be measured easier than body mass index (BMI), among older adults in each generation of late-life for men and women separately.Methods: Three hundred thirty-five participants were used in the current study who were identified by random sampling of residents aged 65-74, 75-84, and 85 + years in Takashima County, Shiga Prefecture, Japan during 2005-2006. Associations between WC and domain-specific cognitive functions measured by 12 neuropsychological tests were examined using multivariable linear regression models with covariates: age, education, and hypertension.Results: Larger WC was associated with better attention/working memory among 65-74-year old women and with better learning/acquisition among 65-74-year-old men, while larger WC was associated with worse learning/acquisition, memory, attention/working memory, and language/fluency among 75-84-year old men.Conclusion: We found age and sex differences in the association between WC and domain-specific cognitive functions. Among older old men (age 75-84), larger WC had negative effects on various domains including memory, attention, language, and executive functions, while we did not find any negative effects of larger WC on cognition among women in any age groups. [ABSTRACT FROM AUTHOR]

T1-weighted MRI has been extensively used to extract imaging biomarkers and build classification models for differentiating Alzheimer's disease (AD) patients from healthy controls, but only recently have brain connectome networks derived from diffusion-weighted MRI been used to model AD progression and various stages of disease such as mild cognitive impairment (MCI). MCI, as a possible prodromal stage of AD, has gained intense interest recently, since it may be used to assess risk factors for AD. Little work has been done to combine information from both white matter and gray matter, and it is unknown how much classification power the diffusion-weighted MRI-derived structural connectome could provide beyond information available from T1-weighted MRI. In this paper, we focused on investigating whether diffusion-weighted MRI-derived structural connectome can improve differentiating healthy controls subjects from those with MCI. Specifically, we proposed a novel feature-ranking method to build classification models using the most highly ranked feature variables to classify MCI with healthy controls. We verified our method on two independent cohorts including the second stage of Alzheimer's Disease Neuroimaging Initiative (ADNI2) database and the National Alzheimer's Coordinating Center (NACC) database. Our results indicated that 1) diffusion-weighted MRI-derived structural connectome can complement T1-weighted MRI in the classification task; 2) the feature-rank method is effective because of the identified consistent T1-weighted MRI and network feature variables on ADNI2 and NACC. Furthermore, by comparing the top-ranked feature variables from ADNI2, NACC, and combined dataset, we concluded that cross-validation using independent cohorts is necessary and highly recommended. [ABSTRACT FROM AUTHOR]

Background: Clinical trials increasingly aim to retard disease progression during presymptomatic phases of Mild Cognitive Impairment (MCI) and thus recruiting study participants at high risk for developing MCI is critical for cost-effective prevention trials. However, accurately identifying those who are destined to develop MCI is difficult. Collecting biomarkers is often expensive. Methods: We used only noninvasive clinical variables collected in the National Alzheimer's Coordinating Center (NACC) Uniform Data Sets version 2.0 and applied machine learning techniques to build a low-cost and accurate Mild Cognitive Impairment (MCI) conversion prediction calculator. Cross-validation and bootstrap were used to select as few variables as possible accurately predicting MCI conversion within 4 years. Results: A total of 31,872 unique subjects, 748 clinical variables, and additional 128 derived variables in NACC data sets were used. About 15 noninvasive clinical variables are identified for predicting MCI/aMCI/naMCI converters, respectively. Over 75% Receiver Operating Characteristic Area Under the Curves (ROC AUC) was achieved. By bootstrap we created a simple spreadsheet calculator which estimates the probability of developing MCI within 4 years with a 95% confidence interval. Conclusions: We achieved reasonably high prediction accuracy using only clinical variables. The approach used here could be useful for study enrichment in preclinical trials where enrolling participants at risk of cognitive decline is critical for proving study effi- cacy, and also for developing a shorter assessment battery. [ABSTRACT FROM AUTHOR]

Introduction: The neuropsychological battery of the Uniform Data Set (UDSNB) was implemented in 2005 by the National Institute on Aging (NIA) Alzheimer Disease Centers program to measure cognitive performance in dementia and mild cognitive impairment due to Alzheimer Disease. This paper describes a revision, the UDSNB 3.0.Methods: The Neuropsychology Work Group of the NIA Clinical Task Force recommended revisions through a process of due diligence to address shortcomings of the original battery. The UDSNB 3.0 covers episodic memory, processing speed, executive function, language, and constructional ability. Data from 3602 cognitively normal participants in the National Alzheimer Coordinating Center database were analyzed.Results: Descriptive statistics are presented. Multivariable linear regression analyses demonstrated score differences by age, sex, and education and were also used to create a normative calculator available online.Discussion: The UDSNB 3.0 neuropsychological battery provides a valuable non proprietary resource for conducting research on cognitive aging and dementia. [ABSTRACT FROM AUTHOR]

Purpose of the Study: We evaluated the feasibility and reliability of commonly used clinical dementia assessments when administered via direct-to-home telemedicine videoconferencing. To date, few studies assessed the suitability of these measures when used in this setting. Design and Methods: Sixty-six participants (33 patients with Alzheimer's disease (AD) and their 33 caregivers) consented to assessment with a battery of tests in both the clinic setting and via telemedicine. We administered cognitive, behavior, and mood assessments to persons with mild, moderate, and severe AD both in the clinic setting and via direct-to-home telemedicine videoconferencing; test-retest reliability was assessed. We also explored how three caregiver measures performed when administered via telemedicine. Assessments were administered 2 weeks apart. Participant feedback about their experience was solicited. Results: Twenty-eight dyads completed the assessments. Reliability was found to be good to excellent in all measures when used with direct-to-home telemedicine. For the most part, participants and clinicians found telemedicine to be a feasible option for assessing cognitive function and caregiver coping. Implications: Findings indicate that these measures can be used to assess persons with AD, as well as their caregivers, across the telemedicine platform, directly to their homes. Use of this technology can expand access to care to the millions across the United States with AD and their caregivers. [ABSTRACT FROM AUTHOR]

Traditionally, assessment of functional and cognitive status of individuals with dementia occurs in brief clinic visits during which time clinicians extract a snapshot of recent changes in individuals' health. Conventionally, this is done using various clinical assessment tools applied at the point of care and relies on patients' and caregivers' ability to accurately recall daily activity and trends in personal health. These practices suffer from the infrequency and generally short durations of visits. Since 2004, researchers at the Oregon Center for Aging and Technology (ORCATECH) at the Oregon Health and Science University have been working on developing technologies to transform this model. ORCATECH researchers have developed a system of continuous in-home monitoring using pervasive computing technologies that make it possible to more accurately track activities and behaviors and measure relevant intra-individual changes. We have installed a system of strategically placed sensors in over 480 homes and have been collecting data for up to 8 years. Using this continuous in-home monitoring system, ORCATECH researchers have collected data on multiple behaviors such as gait and mobility, sleep and activity patterns, medication adherence, and computer use. Patterns of intra-individual variation detected in each of these areas are used to predict outcomes such as low mood, loneliness, and cognitive function. These methods have the potential to improve the quality of patient health data and in turn patient care especially related to cognitive decline. Furthermore, the continuous real-world nature of the data may improve the efficiency and ecological validity of clinical intervention studies. [ABSTRACT FROM AUTHOR]

Background. The age-specific prevalence and incidence of dementia and cognitive impairment in the United States have either remained stable or even slightly declined during the 1980s–1990s. A suggested but untested reason for this improvement in cognitive function over time is higher educational attainment among more recent cohorts. Methods. We used data from two large prospective population-based epidemiological dementia studies conducted in two adjacent regions during the period 1987–2012. We examined whether (i) cohort effects could be observed in age-associated trajectories of cognitive functions and (ii) the observed cohort effects could be explained by educational attainment. Trajectories of neuropsychological tests tapping three domains (psychomotor speed, executive function, and language) were compared among cohorts born between 1902 and 1911, 1912 and 1921, 1922 and 1931, and 1932 and 1943. We examined Age × Cohort interactions in mixed-effects models with/without controlling for education effects. Results. Cohort effects in age-associated trajectories were observed in all three domains, with consistent differences between the earliest born cohort and the most recent cohort. Executive functions showed the strongest and persistent differences between the most recent and other three cohorts. Education did not attenuate any of these associations. Conclusions. Cohort effects were observed in all examined cognitive domains and, surprisingly, remained significant after controlling for educational effects. Factors other than education are likely responsible for the cohort effects in cognitive decline. [ABSTRACT FROM PUBLISHER]

We cross-sectionally examined which lipid profiles are associated with better cognitive function among those aged 80 and older, free of dementia (Clinical Dementia Rating ≤0.5), functionally independent, and community-dwelling. Our cohort consisted of 193 participants from the 'Keys to Optimal Cognitive Aging (KOCOA) Project', a prospective cohort study in Okinawa, Japan. Higher low-density lipoprotein cholesterol levels and lower triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratios were associated with higher scores in memory performance after controlling for confounders. Further research is required to clarify the associations among LDL-C levels, TG/HDL-C ratios, and healthy cognitive aging. [ABSTRACT FROM AUTHOR]

There is a paucity of data regarding trends in dementia and its subtype prevalence in Japan. Our aims in the current paper are to: (1) summarize epidemiological studies of dementia in Japan including relevant details of study protocol and diagnostic criteria, (2) compare the age-specific prevalence of all-cause dementia among studies, and (3) assess the trends in Alzheimer's disease (AD) versus vascular dementia (VaD) over time. We reviewed diagnostic criteria, all-cause dementia prevalence, and the AD/VaD ratio from 8 large population studies of dementia in Japan. Compared with the Okinawa 1992 study, studies conducted in 1994, 1998, 2005, and 2008 had a higher prevalence of all-cause dementia using Poisson regression models, after controlling for age and sex. In contrast to the US and some European countries, all-cause dementia prevalence is increasing in Japan. The prevalence of AD as opposed to VaD seems to be increasing over time, but large variability in diagnostic criteria, possible regional variability, and differences in prevalence of subtypes of dementia between men and women make it difficult to draw a conclusion about this trend at the national level. Further studies, for example, comparing the population attributable risk of vascular diseases to the prevalence and incidence of dementia could help to clarify the regional variations in etiological subtypes. [ABSTRACT FROM AUTHOR]

Aim: It is highly desirable to develop a neuropsychological screening test which is sensitive to the early stage of Alzheimer's disease (AD), and is easy to administer at the primary care physician's (PCP's) office. Methods: Participants were 128 AD patients and 54 healthy volunteers. Brief cognitive screening tests were administered to the participants including the Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Verbal Fluency Test (VFT), a Verbal Category Cued Memory test (CCMT) and the Scenery Picture Memory Test (SPMT). In the SPMT, a scenery picture of a living room containing 23 familiar objects was used. The administration of the SPMT comprised the first shallow memory session (Pict 1) and the second deep memory session (Pict 2). The area under the receiver–operator curve (AUC) was used to compare the efficacy of SPMT with other cognitive tests. Results: Pict 1, which requires less than 2 min to complete, had the same AUC as Pict 2, and showed significantly larger AUC than MMSE, CDT and VFT for all (MMSE 19–23) and very mild (MMSE ≥ 24) AD patients. When we conducted the similar analysis separately for those younger than 75 years and those aged 75 years or older, we obtained the same results as above among the older age group. Pict 1 showed larger AUC than CCMT in overall sample and also in the older age group, although the difference was not statistically significant. Conclusion: The SPMT could be useful for detection of mild and very mild AD in settings even where time is limited. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To compare, in a longitudinal cohort study, declines in specific cognitive domains on their ability to predict time to death, in the presence and absence of dementia, and to explore an explanatory role for vascular disease. DESIGN: Prospective population-based epidemiological study. SETTING: The mid-Monongahela valley of southwestern Pennsylvania from 1987 to 2002. PARTICIPANTS: Nine hundred eighty-nine community-dwelling adults aged 65 and older enrolled in the Monongahela Valley Independent Elders Survey. MEASUREMENTS: Biennial assessments of a range of cognitive domains for up to 12 years. Mortality was modeled as a function of decline in each domain, adjusting for vascular diseases and stratified according to age (≤75 (younger-old) and >75 (older-old)) using Cox proportional hazards modeling. RESULTS: Average annual declines in almost all cognitive domains were significant predictors of mortality in the cohort as a whole. However, after adjustment for dementia, only general cognition, processing speed, the language composite, and the executive function composite remained significant. Adjustment for vascular diseases did not alter the results. In the younger-old group, decline in memory (hazard ratio (HR)=21.4) and executive function (HR=25.5) remained strong predictors after adjustment for dementia and vascular disease. In the older-old group, decline in processing speed was a strong predictor of mortality before (HR=7.4) and after (HR=5.3) controlling for dementia and vascular diseases. CONCLUSION: Decline in most cognitive domains predicted mortality across the cohort, but declines in memory and learning were not independent of dementia. Different domains predicted mortality in the younger and older subgroups. [ABSTRACT FROM AUTHOR]

Background. Cognitive impairment in general is known to predict functional disability, but it is not clear whether performance on specific cognitive domains predicts future disability trends among nondemented elderly persons. Methods. In a representative elderly community-based cohort over up to 10 years of follow-up, we examined predictors of longitudinal trajectories in ability to perform Instrumental Activities of Daily Living (IADL) among nondemented elderly persons. We used trajectory analyses to identify homogeneous groups with respect to trends over time in the numbers of IADL disabilities and their association with baseline demographics, social engagement, depression, physical well-being, and general and domain-specific cognitive functions. We excluded from these analyses those individuals found to have dementia at baseline or at any time during follow-up. Results. Trajectory analysis revealed three homogeneous latent groups which we characterized as No Decline (no decline in abilities to perform IADL tasks over the course of study), Moderate Decline (some functional decline), and Sharp Decline (steep functional decline followed by death). Compared to the Sharp Decline group, the No Decline group was associated with higher baseline functions in all cognitive domains, and the Moderate Decline group was associated with higher baseline functions in all cognitive domains except psychomotor speed and naming. The Moderate and No Decline groups did not differ on any cognitive measure. Conclusion. Among community dwelling elderly persons who remained free from dementia throughout the study, poorer scores in all cognitive domains predicted sharp functional decline followed by death. [ABSTRACT FROM AUTHOR]