Episodic memory performance in a multi-ethnic longitudinal study of 13,037 elderly

Age-related changes in memory are not uniform, even in the absence of dementia. Characterization of non-disease associated cognitive changes is crucial to gain a more complete understanding of brain aging. Episodic memory was investigated in 13,037 ethnically diverse elderly (ages 72 to 85 years) with two to 15 years of follow-up, and with known dementia status, age, sex, education, and APOE genotypes. Adjusted trajectories of episodic memory performance over time were estimated using Latent Class Mixed Models. Analysis was conducted using two samples at baseline evaluation: i) non-cognitively impaired individuals, and ii) all individuals regardless of dementia status. We calculated the age-specific annual incidence rates of dementia in the non-demented elderly (n = 10,220). Two major episodic memory trajectories were estimated: 1) Stable—consisting of individuals exhibiting a constant or improved memory function, and 2) Decliner—consisting of individuals whose memory function declined. The majority of the study participants maintain their memory performance over time. Compared to those with Stable trajectory, individuals characterized as Decliners were more likely to have non-white ethnic background, fewer years of education, a higher frequency of ε4 allele at APOE gene and five times more likely to develop dementia. The steepest decline in episodic memory was observed in Caribbean-Hispanics compared to non-Hispanic whites (p = 4.3 x 10−15). The highest incident rates of dementia were observed in the oldest age group, among those of Caribbean-Hispanics ancestry and among Decliners who exhibited rates five times higher than those with Stable trajectories (11 per 100 person-years versus 3 per 100 person-years. Age, education, ethnic background and APOE genotype influence the maintenance of episodic memory. Declining memory is one of the strongest predictors of incident dementia

Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score

Background Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. Methods and findings Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer’s Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10−5 ). We then integrated these AD-associated SNPs into a Cox proportional hazard model using genotype data from a subset of 6,409 AD patients and 9,386 older controls from Phase 1 of the Alzheimer’s Disease Genetics Consortium (ADGC), providing a polygenic hazard score (PHS) for each participant. By combining population-based incidence rates and the genotype-derived PHS for each individual, we derived estimates of instantaneous risk for developing AD, based on genotype and age, and tested replication in multiple independent cohorts (ADGC Phase 2, National Institute on Aging Alzheimer’s Disease Center [NIA ADC], and Alzheimer’s Disease Neuroimaging Initiative [ADNI], total n = 20,680). Within the ADGC Phase 1 cohort, individuals in the highest PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE ε3/3 individuals, the PHS modified expected age of AD onset by more than 10 y between the lowest and highest deciles (hazard ratio 3.34, 95% CI 2.62–4.24, p = 1.0 × 10−22). In independent cohorts, the PHS strongly predicted empirical age of AD onset (ADGC Phase 2, r = 0.90, p = 1.1 × 10−26) and longitudinal progression from normal aging to AD (NIA ADC, Cochran–Armitage trend test, p = 1.5 × 10−10), and was associated with neuropathology (NIA ADC, Braak stage of neurofibrillary tangles, p = 3.9 × 10−6 , and Consortium to Establish a Registry for Alzheimer’s Disease score for neuritic plaques, p = 6.8 × 10−6 ) and in vivo markers of AD neurodegeneration (ADNI, volume loss within the entorhinal cortex, p = 6.3 × 10−6 , and hippocampus, p = 7.9 × 10−5 ). Additional prospective validation of these results in non-US, non-white, and prospective community-based cohorts is necessary before clinical use. Conclusions We have developed a PHS for quantifying individual differences in age-specific genetic risk for AD. Within the cohorts studied here, polygenic architecture plays an important role in modifying AD risk beyond APOE. With thorough validation, quantification of inherited genetic variation may prove useful for stratifying AD risk and as an enrichment strategy in therapeutic trials

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition

Perceived burden among caregivers of patients with frontotemporal degeneration in the United States

Frontotemporal degeneration (FTD) dementia often begins before age 60 and predominantly presents as four subtypes with prominent features of language, behavior, cognition, and motor symptoms. The early onset and unique symptoms place a distinct burden on caregivers of individuals with FTD versus other dementia types, such as Alzheimer's disease. This is the first known study to examine the domains of the FTD caregiver burden and the caregiver and patient characteristics associated with these domains. In 2017, 674 FTD caregivers in the United States (US) completed a web-based survey of caregiver and patient demographics, disease severity/symptoms, caregiver burden, and financial costs of caregiving. The major factors of caregiver burden (Zarit Burden Inventory) were determined using a principal axis factor analysis with varimax rotation. Multiple linear regression analyses examined caregiver and patient characteristics associated with overall burden and three major factors of burden: role strain, personal strain, and performance strain. Increased neuropsychiatric symptoms was associated with overall caregiver burden and greater role, personal, and performance strain. Younger caregivers experienced greater overall burden and performance strain, female caregivers experienced increased role strain, and male caregivers experienced greater performance strain. Financial costs of caregiving and experiencing a caregiving crisis in the past year were associated with higher overall burden and role strain. This study suggests that the severity and sources of burden differ for caregivers of FTD patients versus patients with other dementia types. Differing predictors for each burden domain suggest targeted interventions to address the unique FTD caregiving challenges

Neighborhood Green Land Cover and Neighborhood-Based Walking in US Older Adults

Introduction: Greenspace exposure has been associated with physical activity, but few studies have investigated its association with physical activity in the residential neighborhood. This study investigates whether greater amounts of neighborhood open space and forest are associated with neighborhood-based walking in older adults. Methods: In 2020, cross-sectional analyses were conducted on those aged >= 65 years from the 2017 National Household Travel Survey. Minutes of neighborhood walking per day were derived from travel diaries. Green land cover measures from the 2011 National Land Cover Dataset were linked to respondent data by the U.S. census tract. Adjusted linear regression models, using weights accounting for survey sampling, tested the associations between the percentage of green land cover in the neighborhood (open space, forest) and minutes of neighborhood walking per day. Adjusted models were stratified to examine whether the associations varied by an individual-and neighborhood-level SES, sex, and race/ethnicity. Results: Respondents (N=72,753) were aged 74 (SD=7) years on average. Greater percentage of open space was associated with more neighborhood walking in African Americans (estimate=0.069, 95% CI=0.005, 0.133). Greater percentage of forest was associated with more neighborhood walking in the overall sample (estimate=0.028, 95% CI=0.006, 0.050), women (estimate=0.025, 95% CI=0.005, 0.045), and Whites (estimate=0.034, 95% CI=0.004, 0.064). Conclusions: Type of neighborhood green land cover (open space versus forest) may be differentially associated with neighborhood walking depending on race/ethnicity. This study suggests a possible association between greater neighborhood open space and greater walking among African Americans that must be confirmed in future studies. Am J Prev Med 2021;61(1):e13-e20. (c) 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved