Explore the vast range of titles available.

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the “LIfestyle for BRAin health” (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta‐analyses with a two‐round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. Highlights An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re‐assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.

100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24·3 million people have dementia today, with 4·6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81·1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.

India, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder. The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) (N = 4,096) is a nationally representative cohort study in India using multistage area probability sampling methods. Using neuropsychological testing and informant reports, we defined DSM-5 mild and major neurocognitive disorder, reported its prevalence, and evaluated criterion and construct validity of the algorithm using clinician-adjudicated Clinical Dementia Ratings (CDR)®. The prevalence of mild and major neurocognitive disorder, weighted to the population, is 17.6% and 7.2%. Demographic gradients with respect to age and education conform to hypothesized patterns. Among N = 2,390 participants with a clinician-adjudicated CDR, CDR ratings and DSM-5 classification agreed for N = 2,139 (89.5%) participants. The prevalence of dementia in India is higher than previously recognized. These findings, coupled with a growing number of older adults in the coming decades in India, have important implications for society, public health, and families. We are aware of no previous Indian population-representative estimates of mild cognitive impairment, a group which will be increasingly important in coming years to identify for potential therapeutic treatment.

Background Blood-based biomarkers are gaining grounds for the detection of Alzheimer’s disease (AD) and related disorders (ADRDs). However, two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction. A novel proteomic method for pre-selected analytes, based on proximity extension technology, was recently introduced. Referred to as the NULISAseq CNS disease panel, the assay simultaneously measures ~ 120 analytes related to neurodegenerative diseases, including those linked to both core (i.e., tau and amyloid-beta (Aβ)) and non-core AD processes. This study aimed to evaluate the technical and clinical performance of this novel targeted proteomic panel. Methods The NULISAseq CNS disease panel was applied to 176 plasma samples from 113 individuals in the MYHAT-NI cohort of predominantly cognitively normal participants from an economically underserved region in southwestern Pennsylvania, USA. Classical AD biomarkers, including p-tau181, p-tau217, p-tau231, GFAP, NEFL, Aβ40, and Aβ42, were independently measured using Single Molecule Array (Simoa) and correlations and diagnostic performances compared. Aβ pathology, tau pathology, and neurodegeneration (AT(N) statuses) were evaluated with [ 11 C] PiB PET, [ 18 F]AV-1451 PET, and an MRI-based AD-signature composite cortical thickness index, respectively. Linear mixed models were used to examine cross-sectional and Wilcoxon rank sum tests for longitudinal associations between NULISA and neuroimaging-determined AT(N) biomarkers. Results NULISA concurrently measured 116 plasma biomarkers with good technical performance (97.2 ± 13.9% targets gave signals above assay limits of detection), and significant correlation with Simoa assays for the classical biomarkers. Cross-sectionally, p-tau217 was the top hit to identify Aβ pathology, with age, sex, and APOE genotype-adjusted AUC of 0.930 (95%CI: 0.878–0.983). Fourteen markers were significantly decreased in Aβ-PET + participants, including TIMP3, BDNF, MDH1, and several cytokines. Longitudinally, FGF2, IL4, and IL9 exhibited Aβ PET-dependent yearly increases in Aβ-PET + participants. Novel plasma biomarkers with tau PET-dependent longitudinal changes included proteins associated with neuroinflammation, synaptic function, and cerebrovascular integrity, such as CHIT1, CHI3L1, NPTX1, PGF, PDGFRB, and VEGFA; all previously linked to AD but only reliable when measured in cerebrospinal fluid. The autophagosome cargo protein SQSTM1 exhibited significant association with neurodegeneration after adjusting age, sex, and APOE ε4 genotype. Conclusions Together, our results demonstrate the feasibility and potential of immunoassay-based multiplexing to provide a comprehensive view of AD-associated proteomic changes, consistent with the recently revised biological and diagnostic framework. Further validation of the identified inflammation, synaptic, and vascular markers will be important for establishing disease state markers in asymptomatic AD.

To estimate and compare the frequency and prevalence of mild cognitive impairment (MCI) and related entities using different classification approaches at the population level. Cross-sectional epidemiologic study of population-based cohort recruited by age-stratified random sampling from electoral rolls. Small-town communities in western Pennsylvania. Of 2,036 individuals aged 65 years and older, 1,982 participants with normal or mildly impaired cognition (age-education-corrected Mini-Mental State scores ≥21). Demographics, neuropsychological assessment expressed as cognitive domains, functional ability, and subjective reports of cognitive difficulties; based on these measurements, operational criteria for the Clinical Dementia Rating (CDR) scale, the 1999 criteria for amnestic MCI, the 2004 Expanded criteria for MCI, and new, purely cognitive criteria for MCI. A CDR rating of 0.5 (uncertain/very mild dementia) was obtained by 27.6% of participants, whereas 1.2% had CDR ≥1 (mild or moderate dementia). Among those with CDR <1, 2.27% had amnestic MCI and 17.66% had expanded MCI, whereas 35.17% had MCI by purely cognitive classification. Isolated executive function impairment was the least common, whereas impairment in multiple domains including executive function was the most common. Prevalence estimates weighted against the U.S. Census are also provided. The manner in which criteria for MCI are operationalized determines the proportion of individuals who are thus classified and the degree of overlap with other criteria. Prospective follow-up is needed to determine progression from MCI to dementia and thus empirically develop improved MCI criteria with good predictive value.

Background: It is of considerable public health importance to prevent or delay the progression of mild cognitive impairment (MCI) to more severely impaired cognitive states. This study examines the risk of progression from mild to severe cognitive impairment in relation to engagement in social activities while mildly impaired and the concurrence of subsequent change in engagement with MCI progression. Methods: Participants were 816 older adults with cognitively defined MCI (mean age 78.0 (standard deviation or SD = 7.4) years) from the Monongahela–Youghiogheny Healthy Aging Team (MYHAT) Study – a prospective cohort study of MCI in the community. Over three years of follow-up, 78 individuals progressed from MCI to severe cognitive impairment, while 738 did not progress. Risk of progression was estimated using discrete time survival analyses. The main predictors were standardized composite measures of the variety and frequency of engagement in social activities. Results: Lower risk of progression from mild to severe cognitive impairment was associated with both a greater level of frequency of engagement in social activities while mildly impaired (OR = 0.72, 95% CI: 0.55–0.93, p = 0.01) and also with a slower rate of decline in the variety of activities over time (OR = 0.01, 95% CI: <0.001–0.38, p = 0.02). Conclusions: Greater engagement in social activities may potentially be beneficial for preventing or delaying further cognitive decline among older adults with MCI. Alternatively, lesser engagement in social activities may be a marker of impending cognitive decline in MCI.

A key component of successful aging is the ability to independently perform instrumental activities of daily living (IADL). We examined the ability to perform multiple IADL tasks in relation to mild cognitive impairment (MCI) defined on purely neuropsychological grounds. Cross-sectional study. Population-based cohort in southwestern Pennsylvania. One thousand seven hundred thirty-seven community-dwelling adults age 65 years and older. Classification of MCI based on performance with reference to norms in the cognitive domains of memory, language, attention, executive, and visuospatial functions. The ability to perform seven IADL tasks (traveling, shopping, preparing meals, doing housework, taking medications, handling personal finances, and using the telephone) as assessed by the Older Americans Resources and Services scale. Those with cognitively defined MCI were more likely to be dependent in at least one IADL task, as well as in each individual IADL task, than cognitively normal participants. Better memory and executive functioning were associated with lower odds of IADL dependence in MCI. Across the subtypes of MCI, those with the multiple-domain amnestic subtype were most likely to be dependent in all IADL tasks, with better executive functioning associated with lower risk of dependence in select IADL tasks in this group. Mild impairment in cognition is associated with difficulty performing IADL tasks at the population level. Understanding these associations may help improve prediction of the outcomes of MCI. It may also allow appropriate targeting of cognitive interventions in MCI to potentially help preserve functional independence.

Introduction Using the ATN framework, we evaluated the potential of plasma biomarkers to identify abnormal brain amyloid-beta (Aβ) positron emission tomography (PET), tau-PET and neurodegeneration in a socioeconomically disadvantaged population-based cohort. Methods Community-dwelling dementia-free ( n  = 113, including 102 (91%) cognitively normal) participants underwent ATN neuroimaging and plasma biomarker assessments. Results Plasma Aβ42/Aβ40, p-tau181, and p-tau217 showed significant associations with Aβ-PET status, (adjusted odds ratio [AOR] of 1.74*10 –24 , 1.47, and 3.43*10 3 , respectively ( p -values < 0.05), with p-tau217 demonstrating the highest classification accuracy for Aβ-PET status (AUC = 0.94). Plasma p-tau181 and p-tau217 showed significant associations with tau-PET status (AOR: 1.50 and 22.24, respectively ( p -values < 0.05), with comparable classification accuracies for tau-PET status (AUC = 0.74 and 0.70, respectively). Only plasma NfL showed significant association with neurodegeneration based on cortical thickness (AOR = 1.09, p -value < 0.05). Conclusion Our findings highlight the potential of plasma p-tau217 as a biomarker for brain Aβ and tau pathophysiology, p-tau181 for tau abnormalities, and NfL for neurodegeneration in the community.

(Am J Geriatr Psychiatry 2011; 19:205–210)

Two papers recently published in IPG point toward decreasing rates of cognitive decline and dementia in high-income countries. (Dodge et al., 2016; Kosteniuk et al., 2016). These reports join the ranks of a growing body of literature on generational trends, or more, specifically, “cohort effects,” in aging, cognitive decline, and dementia.