Sex Differences in Longitudinal Tau-PET in Preclinical Alzheimer Disease: A Meta-Analysis.

Importance: Alzheimer disease (AD) predominates in females at almost twice the rate relative to males. Mounting evidence in adults without AD indicates that females exhibit higher tau deposition than age-matched males, particularly in the setting of elevated β-amyloid (Aβ), but the evidence for sex differences in tau accumulation rates is inconclusive.

Objective: To examine whether female sex is associated with faster tau accumulation in the setting of high Aβ (as measured with positron emission tomography [PET]) and the moderating influence of sex on the association between APOEε4 carrier status and tau accumulation.

Amyloid is associated with accelerated atrophy in cognitively unimpaired individuals.

Introduction: This study examined the association of longitudinal atrophy with baseline cerebrospinal fluid (CSF) amyloid beta (Aβ, A) and phosphorylated tau (p-tau, T) biomarkers (Aβ42/40, p-tau181) in 406 cognitively unimpaired (CU) individuals (6.670 years of follow-up on average, up to 13 imaging visits) to assess whether A+ is associated with Alzheimer's disease-like atrophy and whether this depends on p-tau181 levels.

Methods: An A-T- CU group free from abnormal neurodegeneration (N) was identified using a robust normative approach and used to model normal age-related atrophy via -scoring.

F-MK-6240 tau PET in patients at-risk for chronic traumatic encephalopathy.

Background: Molecular biomarkers of chronic traumatic encephalopathy (CTE) are lacking. We evaluated F-MK-6240 tau PET as a biomarker for CTE. Two studies were done: (1) H-MK-6240 autoradiography and an in-vitro brain homogenate binding studies on postmortem CTE tissue, (2) an in-vivo F-MK-6240 tau PET study in former American football players.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Cerebral Microbleeds and Amyloid Pathology Estimates From the Amyloid Biomarker Study.

Importance: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels.

Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age.

Design, Setting, And Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]).

Evaluating the association of genotype and cognitive resilience in SuperAgers.

Importance: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary memory are underexplored in large, racially diverse cohorts.

Objective: To determine the frequency of genotypes in non-Hispanic Black and non-Hispanic White SuperAgers compared to middle-aged (ages 50-64), old (ages 65-79), and oldest-old (ages 80+) controls and Alzheimer's disease (AD) dementia cases.

Comparison of sample characteristics of Wisconsin Alzheimer's Disease Research Center participants with the Wisconsin state population-An evaluation of the recruitment effort.

Introduction: Understanding how a research sample compares to the population from which it is drawn can help inform future recruitment planning. We compared the Wisconsin Alzheimer's Disease Research Center (WADRC) participant sample to the Wisconsin state population (WI-pop) on key demographic, social exposome, and vascular risk measures.

Methods: The WADRC sample included 930 participants.

BDNF expression mediates verbal learning and memory in women in a cohort enriched with risk for Alzheimer's disease.

Introduction: This study examined whether sex differences in verbal learning and memory (VLM) are mediated by plasma brain-derived neurotrophic factor (BDNF) expression.

Methods: In a sample of  = 201 participants (63.81 ± 6.

Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults.

Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.

Menopausal hormone therapy is associated with worse levels of Alzheimer's disease biomarkers in APOE ε4-carrying women: An observational study.

Introduction: Menopausal hormone therapy (MHT), along with the apolipoprotein E (APOE) ε4 allele, has been suggested as a possible risk factor for Alzheimer's disease (AD). However, the relationship between MHT and cerebrospinal fluid (CSF) biomarkers is unknown: we investigated this association, and whether APOE ε4 carrier status moderates it.

Methods: In an observational study of 136 cognitively unimpaired female participants (M = 66.

Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer's disease identifies cognitive status.

Introduction: Whole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimer's disease (AD) but has not been tested in persons with mild cognitive impairment (MCI).

Methods: We used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU).

Results: WGMS identified 9756 differentially methylated positions (DMPs) in persons with MCI, including 1743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport.

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.

Targeted Proteomic Biomarker Profiling Using NULISA in a cohort enriched with risk for Alzheimer's Disease and Related Dementias.

Introduction: Targeted proteomic assays may be useful for diagnosing and staging Alzheimer's disease and related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning the AD spectrum.

Methods: Cross-sectional plasma samples (n=252) were analyzed using Alamar's NULISAseq CNS panel.

Lower neurovascular coupling response despite higher cerebral blood flow at rest in apolipoprotein ɛ4 positive adults.

Cerebral blood flow at rest declines with age. However, age-related changes in functional measures of cerebrovascular health including cerebrovascular reactivity and neurovascular coupling are not well understood. Additionally, the effect of apolipoprotein E (APOE) ε4, a strong genetic risk factor for Alzheimer's disease, on cerebral blood flow and cerebrovascular function remains unclear.

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI).

The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap.

Visual read of [F-18]florquinitau PET that includes and extends beyond the mesial temporal lobe is associated with increased plasma pTau217 and cognitive decline in a cohort that is enriched with risk for Alzheimer's disease.

Introduction: Patterns of signal from tau positron emission tomography (tau-PET) confined to the medial temporal lobe (MTL) or extended into the neocortex may be relevant for Alzheimer's disease (AD) research if they are linked to differential biomarker levels and cognitive decline.

Methods: Visual assessment of Tau-PET [F-18]florquinitau (FQT) exams from 728 initially non-demented older adults yielded four uptake groups: tau-negative (T-), MTL-only (T+), neocortex-only (T+), or both (T+). Mixed effects models assessed group differences in retrospective cognitive and plasma pTau217 trajectories.

Amyloid-β positivity is less prevalent in cognitively unimpaired KL-VS heterozygotes.

Background: Klotho, encoded by the gene, is an anti-aging and neuroprotective protein. KL-VS heterozygosity (KL-VS) is hypothesized to be protective against the accumulation of Alzheimer's disease (AD) neuropathological hallmarks (amyloid-β (Aβ) and tau).

Objective: We examine whether being positive for Aβ (A+) or tau (T+), or A/T joint status [positive for Aβ (A + T-), tau (A-T+), both (A + T+) or neither (A-T-)] vary by KL-VS and whether serum klotho protein levels vary based on A+, T+, or A/T status in a cohort enriched for AD risk.

Telomere length and cognitive function among middle-aged and older participants from communities underrepresented in aging research: A preliminary study.

Objective: Accelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities, but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults.

Methods: This study included data on telomere length and cognitive test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA.

Misfolded alpha synuclein co-occurrence with Alzheimer's disease proteinopathy.

Introduction: Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded -synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD).

Methods: Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.

Alzheimer's disease genetic risk and changes in brain atrophy and white matter hyperintensities in cognitively unimpaired adults.

Reduced brain volumes and more prominent white matter hyperintensities on MRI scans are commonly observed among older adults without cognitive impairment. However, it remains unclear whether rates of change in these measures among cognitively normal adults differ as a function of genetic risk for late-onset Alzheimer's disease, including -ɛ4, -ɛ2 and Alzheimer's disease polygenic risk scores (AD-PRS), and whether these relationships are influenced by other variables. This longitudinal study examined the trajectories of regional brain volumes and white matter hyperintensities in relationship to genotypes ( = 1541) and AD-PRS ( = 1093) in a harmonized dataset of middle-aged and older individuals with normal cognition at baseline (mean baseline age = 66 years, SD = 9.