Neighborhood Built Environment Characteristics and Cognition in Non-demented Older Adults

Research suggests that neighborhood built environment (BE) characteristics consistent with increasing urban density may be associated with better cognition in older adults; however, few of these studies have been conducted to date. Focusing on older adults, my study aimed to: 1) systematically review studies on neighborhood social and BE and cognition; 2) examine whether social/walking destination density, intersection density, residential/retail land use, distance to nearest bus/train stop, or population density is associated with cognition; and 3) investigate if BE-cognition associations vary by individual-level characteristics (education, race/ethnicity, sex, apolipoprotein e4 genotype [APOE; genetic risk factor for Alzheimer’s disease], or sedentary behavior). I used cross-sectional, Exam 5 data on 4,123 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal study of subclinical cardiovascular disease that began in 2000. MESA recruited from six US regions (New York, Baltimore, Chicago, Los Angeles, Minneapolis-St. Paul, and Winston Salem) and oversampled minorities (Chinese, African American, and Hispanic). The literature review suggested that BE features such as presence of a community center and transit stops, increased land use mix, and public spaces in better condition may be associated with better cognition. Additionally, the literature suggested that lower neighborhood socioeconomic status (SES) is associated with worse cognition, independent of individual-level SES. Aim 2 analyses suggested that increasing population and intersection density are associated with worse cognition, whereas increased land dedicated to retail uses is associated with better cognition. Aim 3 analyses suggested that BE-cognition associations vary significantly by an individual’s education, race/ethnicity, sex, APOE genotype, and sedentary behavior. BE characteristics consistent with increasing urban density were associated with worse cognition in Hispanics but not Whites and in APOE e4 carriers but not APOE e4 non-carriers. Although an increase in neighborhood retail destinations was associated with better cognition in the overall sample, these results suggest that increasing urban density may have a disproportionately negative effect on cognition in racial/ethnic minorities and those with genetic susceptibility for Alzheimer’s disease. Compact growth policies may not be beneficial to all, and thus, planners and public health researchers need to consider the BE’s positive and negative effects on cognition in vulnerable populations.Doctor of Philosoph

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

Outdoor green space exposure and brain health measures related to Alzheimer’s disease: a rapid review

Objectives Summarise studies of outdoor green space exposure and brain health measures related to Alzheimer’s disease and related disorders (ADRD), and determine scientific gaps for future research.Design Rapid review of primary research studies.Methods and outcomes PubMed, Embase and Web of Science Core Collection were searched for articles meeting the criteria published on/before 13 February 2020. The review excluded papers not in English, focused on transient states (eg, mental fatigue) or not using individual-level measures of brain health (eg, average school test scores). Brain health measures of interest included cognitive function, clinical diagnosis of cognitive impairment/dementia/ADRD and brain biomarkers such as those from MRI, measures typically associated with ADRD risk and disease progression.Results Twenty-two papers were published from 2012 to 2020, 36% on &lt;18 years old, 32% on 18–64 years old and 59% on ≥65 years old. Sixty-four per cent defined green space based on the Normalised Difference Vegetation Index (‘greenness’/healthy vegetation) and 68% focused on cognitive measures of brain health (eg, memory). Seventeen studies (77%) found green space-brain health associations (14 positive, 4 inverse). Greater greenness/green space was positively associated various cognitive domains in 10 studies and with MRI outcomes (regional brain volumes, cortical thickness, amygdala integrity) in three studies. Greater neighbourhood greenness was associated with lower odds/risk of cognitive impairment/ADRD in some studies but increased odds/risk in others (n=4 studies).Conclusions Published studies suggest positive green space-brain health associations across the life course, but the methods and cohorts were limited and heterogeneous. Future research using racially/ethnically and geographically diverse cohorts, life course methods and more specific green space and brain health measures (eg, time spent in green spaces, ADRD biomarkers) will strengthen evidence for causal associations