Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.

Loneliness, cerebrovascular and Alzheimer's disease pathology, and cognition.

Introduction: Loneliness has a rising public health impact, but research involving neuropathology and representative cohorts has been limited.

Methods: Inverse odds of selection weights were generalized from the autopsy sample of Rush Alzheimer's Disease Center cohorts (N = 680; 89 ± 9 years old; 25% dementia) to the US-representative Health and Retirement Study (N = 8469; 76 ± 7 years old; 5% dementia) to extend external validity. Regressions tested cross-sectional associations between loneliness and (1) Alzheimer's disease (AD) and cerebrovascular pathology; (2) five cognitive domains; and (3) relationships between pathology and cognition, adjusting for depression.

Sex, racial, and -ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

Introduction: The effects of sex, race, and Apolipoprotein E () - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized.

Methods: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.

Exercise: Just What the Doctor Ordered, But Why? Elucidating Mechanisms for Women's Increased High-Density Lipoprotein Benefit From Exercise and for the Health ABC Study.

High-density lipoprotein (HDL) is protective against cardiovascular disease. Exercise can increase HDL concentration, and some evidence suggests that this effect occurs more strongly in women than in men. Both HDL and exercise are associated with inflammation.

Promoting diverse perspectives: Addressing health disparities related to Alzheimer's and all dementias.

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups.

Small vessel cerebrovascular disease is associated with cognition in prospective Alzheimer's clinical trial participants.

Background: Secondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions.

Riding the merry-go-round of racial disparities in ADRD research.

Introduction: With the rapid expansion of the aging population, the burden of Alzheimer's disease related dementias (ADRD) is anticipated to increase in racialized and minoritized groups who are at disproportionately higher risk. To date, research emphasis has been on further characterizing the existence of racial disparities in ADRD through comparisons to groups racialized as White that are assumed to be normative. Much of the literature on this comparison insinuates that racialized and minoritized groups experience poorer outcomes due to genetics, culture, and/or health behaviors.

Representativeness of samples enrolled in Alzheimer's disease research centers.

Unlabelled: To generalize findings on the mechanisms and prognosis in Alzheimer's disease and related dementias (ADRD), it is critical for ADRD research to be representative of the population. Sociodemographic and health characteristics across ethnoracial groups included in the National Alzheimer's Coordinating Center sample (NACC) were compared to the nationally representative Health and Retirement Study (HRS). Baseline NACC data ( = 36,639) and the weighted 2010 HRS wave ( = 52,071,840) were included.

Subjective cognitive decline across ethnoracial groups in the A4 study.

Introduction: The associations between subjective cognitive decline (SCD), cognition, and amyloid were explored across diverse participants in the A4 study.

Methods: Five thousand one hundred and fifty-one non-Hispanic White, 262 non-Hispanic Black, 179 Hispanic-White, and 225 Asian participants completed the Preclinical Alzheimer Cognitive Composite (PACC), self- and study partner-reported Cognitive Function Index (CFI). A subsample underwent amyloid positron emission tomography ( F-florbetapir) (N = 4384).

A simple genetic stratification method for lower cost, more expedient clinical trials in early Alzheimer's disease: A preliminary study of tau PET and cognitive outcomes.

Introduction: Identifying individuals who are most likely to accumulate tau and exhibit cognitive decline is critical for Alzheimer's disease (AD) clinical trials.

Methods: Participants (N = 235) who were cognitively normal or with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative were stratified by a cutoff on the polygenic hazard score (PHS) at 65th percentile (above as high-risk group and below as low-risk group). We evaluated the associations between the PHS risk groups and tau positron emission tomography and cognitive decline, respectively.

Identification of Sex-Specific Genetic Variants Associated With Tau PET.

Background And Objectives: Important sex differences exist in tau pathology along the Alzheimer disease (AD) continuum, with women showing enhanced tau deposition compared with men, especially during the mild cognitive impairment (MCI) phase. This study aims to identify specific genetic variants associated with sex differences in regional tau aggregation, as measured with PET.

Methods: Four hundred ninety-three participants (women, n = 246; men, n = 247) who self-identified as White from the AD Neuroimaging Initiative study, with genotyping data and F-Flortaucipir tau PET data, were included irrespective of clinical diagnosis (cognitively normal [CN], MCI, and AD).

Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging.

Importance: Disrupted sleep is common in aging and is associated with cognition. Age-related changes to sleep are associated with multiple causes, including early Alzheimer disease pathology (amyloid β [Aβ]), depression, and cardiovascular disease.

Objective: To investigate the associations between self-reported sleep duration and brain Aβ burden as well as the demographic, cognitive, and lifestyle variables in adults with normal cognition.

KL∗VS heterozygosity reduces brain amyloid in asymptomatic at-risk APOE∗4 carriers.

KLOTHO∗VS heterozygosity (KL∗VS) was recently shown to be associated with reduced risk of Alzheimer's disease (AD) in APOE∗4 carriers. Additional studies suggest that KL∗VS protects against amyloid burden in cognitively normal older subjects, but sample sizes were too small to draw definitive conclusions. We performed a well-powered meta-analysis across 5 independent studies, comprising 3581 pre-clinical participants ages 60-80, to investigate whether KL∗VS reduces the risk of having an amyloid-positive positron emission tomography scan.

TOMM40-APOE haplotypes are associated with cognitive decline in non-demented Blacks.

Introduction: The goal was to investigate effects of APOE-TOMM40-'523 haplotypes on cognitive decline in non-demented non-Hispanic Blacks (NHB), and determine whether effects differ from non-Hispanic Whites (NHW).

Methods: The impact of zero to two copies of the '523-Short variant (S; poly-T alleles < 20) within apolipoprotein E (APOE) genotype on a composite measure of global cognition and five domains was examined.

Results: In NHB with ε3/ε3 (N = 294), '523-S/S was associated with faster decline in global cognition (β = -0.

Amyloid PET Imaging in Self-Identified Non-Hispanic Black Participants of the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) Study.

Objective: To examine whether amyloid PET in cognitively normal (CN) individuals screened for the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) study differed across self-identified non-Hispanic White and Black (NHW and NHB) groups.

Methods: We examined 3,689 NHW and 144 NHB participants who passed initial screening for the A4 study and underwent amyloid PET. The effect of race on amyloid PET was examined using logistic (dichotomous groups) and linear (continuous values) regression controlling for age, sex, and number of ε4 and ε2 alleles.

Education differentially contributes to cognitive reserve across racial/ethnic groups.

Introduction: We examined whether educational attainment differentially contributes to cognitive reserve (CR) across race/ethnicity.

Methods: A total of 1553 non-Hispanic Whites (Whites), non-Hispanic Blacks (Blacks), and Hispanics in the Washington Heights-Inwood Columbia Aging Project (WHICAP) completed structural magnetic resonance imaging. Mixture growth curve modeling was used to examine whether the effect of brain integrity indicators (hippocampal volume, cortical thickness, and white matter hyperintensity [WMH] volumes) on memory and language trajectories was modified by education across racial/ethnic groups.

Genome-wide association study of language performance in Alzheimer's disease.

Language impairment is common in prodromal stages of Alzheimer's disease (AD) and progresses over time. However, the genetic architecture underlying language performance is poorly understood. To identify novel genetic variants associated with language performance, we analyzed brain MRI and performed a genome-wide association study (GWAS) using a composite measure of language performance from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=1560).

Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease.

Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study.

Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis.

[(11)C]PiB PET in Gerstmann-Sträussler-Scheinker disease.

Gerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [(11)C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [(11)C]PiB PET scans using standard methods.

Cerebral hypometabolism and grey matter density in MAPT intron 10 +3 mutation carriers.

Multiple systems tauopathy with presenile dementia (MSTD), a form of frontotemporal dementia with parkinsonism-17 with tau inclusions (FTDP-17T), is a neurodegenerative disorder caused by an (a) to (g) transition at position +3 of intron 10 of the microtubule associated protein tau (MAPT) gene. The mutation causes overexpression of 4 repeat (4R) tau isoforms with increased 4R/3R ratio leading to neurodegeneration. Clinically, these patients primarily present with behavioral variant FTD (bvFTD) and show disinhibition, disordered social comportment, and impaired executive function, memory, and speech.