Early life exposure to structural sexism and late-life memory trajectories among black and white women and men in the United States.

Introduction: We investigated whether early life exposure to state-level structural sexism influenced late-life memory trajectories among United Staes (U.S.) -born women and men and determined whether associations differed between racialized groups.

Marital status, brain health, and cognitive reserve among diverse older adults.

Objective: Being married may protect late-life cognition. Less is known about living arrangement among unmarried adults and mechanisms such as brain health (BH) and cognitive reserve (CR) across race and ethnicity or sex/gender. The current study examines (1) associations between marital status, BH, and CR among diverse older adults and (2) whether one's living arrangement is linked to BH and CR among unmarried adults.

Metabolite signatures of chronological age, aging, survival, and longevity.

Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk.

Overweight as a Causal Factor Contributing to Better Survival at the Oldest Old Ages: A Mendelian Randomization Study.

Overweight, defined by a body mass index (BMI) between 25 and 30, has been associated with enhanced survival among older adults in some studies. However, whether being overweight is causally linked to longevity remains unclear. To investigate this, we conducted a Mendelian randomization (MR) study of lifespan 85+ years, using overweight as an exposure variable and data from the Health and Retirement Study and the Long Life Family Study.

A pathway linking pulse pressure to dementia in adults with Down syndrome.

Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy.

Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome.

Introduction: People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials.

Physical Activity Moderates the Relationship between Cardiovascular Disease Risk Burden and Cognition in Older Adults.

Introduction: Older individuals with a higher cardiovascular disease (CVD) burden have a higher risk for accelerated cognitive decline and dementia. Physical activity (PA) is an inexpensive and accessible preventive measure to CVD, cognitive impairment, and dementia. The current study examined (1) whether PA moderates the relationship between CVD burden and cognition and (2) whether the moderating effect of PA differs by race/ethnicity groups and by APOE-ɛ4 status.

Prodromal Alzheimer's disease can affect activities of daily living for adults with Down syndrome.

Introduction: Alzheimer's disease (AD) affecting adults with Down syndrome (DS-AD), like late-onset AD (LOAD) in the neurotypical population, has preclinical, prodromal, and more advanced stages. Only tasks placing high demands on cognition are expected to be affected during the prodromal stage, with activities of daily living (ADLs) typically being spared. However, cognitive demands of ADLs could be high for adults with DS and may be affected during prodromal DS-AD.

Systemic inflammation in relation to exceptional memory in the Long Life Family Study (LLFS).

Background And Objectives: We previously found a substantial familial aggregation of healthy aging phenotypes, including exceptional memory (EM) in long-lived persons. In the current study, we aim to assess whether long-lived families with EM and without EM (non-EM) differ in systemic inflammation status and trajectory.

Methods: The current study included 4333 participants of the multi-center Long Life Family Study (LLFS).

Pathways linking pulse pressure to dementia in adults with Down syndrome.

Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS.

Individualized estimated years from onset of Alzheimer's disease- related decline for adults with Down syndrome.

Introduction: Adults with Down syndrome (DS) are at increased risk for Alzheimer's disease (AD) and vary in their age of transition from AD preclinical to prodromal or more advanced clinical stages. An empirically based method is needed to determine individual "estimated years from symptom onset (EYO)," the same construct used in studies of autosomal dominant AD .

Methods: Archived data from a previous study of > 600 adults with DS were examined using survival analysis methods.

Semantic item-level metrics relate to future memory decline beyond existing cognitive tests in older adults without dementia.

In normal aging, the cognitive domain of semantic memory remains preserved, while the domain of episodic memory declines to some extent. In Alzheimer's disease dementia, both semantic and episodic memory become impaired early in the disease process. Given the need to develop sensitive and accessible cognitive markers for early detection of dementia, we investigated among older adults without dementia whether item-level metrics of semantic fluency related to episodic memory decline above and beyond existing neuropsychological measures and total fluency score.

Low Risk for Developing Diabetes Among the Offspring of Individuals With Exceptional Longevity and Their Spouses.

Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.

Rare genetic variants correlate with better processing speed.

We conducted a genome-wide association study of Digit Symbol Substitution Test scores administered in 4207 family members of the Long Life Family Study (LLFS). Genotype data were imputed to the HRC panel of 64,940 haplotypes resulting in ∼15M genetic variants with a quality score > 0.7.

Brain Aging Among Racially and Ethnically Diverse Middle-Aged and Older Adults.

Importance: Neuroimaging studies have documented racial and ethnic disparities in brain health in old age. It remains unclear whether these disparities are apparent in midlife.

Objective: To assess racial and ethnic disparities in magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration in midlife and late life.

APOE ɛ4 allele and TOMM40-APOC1 variants jointly contribute to survival to older ages.

Age-related diseases characteristic of post-reproductive life, aging, and life span are the examples of polygenic non-Mendelian traits with intricate genetic architectures. Polygenicity of these traits implies that multiple variants can impact their risks independently or jointly as combinations of specific variants. Here, we examined chances to live to older ages, 85 years and older, for carriers of compound genotypes comprised of combinations of genotypes of rs429358 (APOE ɛ4 encoding polymorphism), rs2075650 (TOMM40), and rs12721046 (APOC1) polymorphisms using data from four human studies.

A modified Cued Recall Test for detecting prodromal AD in adults with Down syndrome.

Introduction: The development of valid methods to diagnose prodromal Alzheimer's disease (AD) in adults with Down syndrome (DS) is one of the many goals of the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS).

Methods: The diagnostic utility of a modified Cued Recall Test (mCRT) was evaluated in 332 adults with DS ranging from 25 to 81 years of age. Total recall was selected a priori, as the primary indicator of performance.

Correction: Hom et al. Cognitive Function during the Prodromal Stage of Alzheimer's Disease in Down Syndrome: Comparing Models. 2021, , 1220.

We would like to submit the following correction to our recently published paper [...

Effects of Sex, APOE4, and Lifestyle Activities on Cognitive Reserve in Older Adults.

Background And Objectives: Lifestyle activities, such as physical activity and cognitive stimulation, may mitigate age-associated cognitive decline, delay dementia onset, and increase cognitive reserve. Whether the association between lifestyle activities and cognitive reserve differs by sex and APOE4 status is an understudied yet critical component for informing targeted prevention strategies. The current study examined interactions between sex and physical or cognitive activities on cognitive reserve for speed and memory in older adults.

Association between late maternal age and age-related endophenotypes in the Long Life Family Study.

Extended maternal age has been suggested as marker of delayed age-associated disabilities. We use the Long Life Family Study (LLFS) offspring generation to investigate the association between extended maternal age at last childbirth and healthy-aging endophenotypes. We hypothesize that women with extended maternal age at last childbirth will exhibit healthier endophenotype profiles compared to younger mothers.