State Schooling Policies and Cognitive Performance Trajectories: A Natural Experiment in a National US Cohort of Black and White Adults.

Background: Education is strongly associated with cognitive outcomes at older ages, yet the extent to which these associations reflect causal effects remains uncertain due to potential confounding.

Methods: Leveraging changes in historical measures of state-level education policies as natural experiments, we estimated the effects of educational attainment on cognitive performance over 10 years in 20,248 non-Hispanic Black and non-Hispanic White participants, aged 45+ in the Reasons for Geographic and Racial Disparities in Stroke cohort (2003-2020) by (1) using state- and year-specific compulsory schooling laws, school-term length, attendance rate, and student-teacher ratio policies to predict educational attainment for US Census microsample data from 1980 and 1990, and (2) applying policy-predicted years of education (PPYEd) to predict memory, verbal fluency, and a cognitive composite. We estimated overall and race- and sex-specific effects of PPYEd on level and change in each cognitive outcome using random intercept and slope models, adjusting for age, year of first cognitive assessment, and indicators for state of residence at age 6.

Visual Impairment, Eye Conditions, and Diagnoses of Neurodegeneration and Dementia.

Importance: Vision and eye conditions are associated with increased risk for Alzheimer disease and related dementias (ADRDs), but the nature of the association and the underlying biological pathways remain unclear. If causal, vision would be an important modifiable risk factor with viable population-level interventions.

Objective: To evaluate potentially causal associations between visual acuity, eye conditions (specifically cataracts and myopia), neuroimaging outcomes, and ADRDs.

Snoring and risk of dementia: a prospective cohort and Mendelian randomization study.

Study Objectives: The association between snoring, a very common condition that increases with age, and dementia risk is controversial. We aimed to investigate the observational and causal relationship between snoring and dementia, and to elucidate the role of body mass index (BMI).

Methods: Using data from 451 250 participants who were dementia-free at baseline, we examined the association between self-reported snoring and incident dementia using Cox proportional-hazards models.

Dementia Risk Scores, , and risk of Alzheimer disease: one size does not fit all.

Introduction: Evaluating the generalizability of dementia risk scores, primarily developed in non-Latinx White (NLW) participants, and interactions with genetic risk factors in diverse populations is crucial for addressing health disparities.

Methods: We analyzed the association of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) and modified CAIDE (mCAIDE) scores with dementia risk using logistic regression models stratified by race/ethnicity in NACC and ADNI, and assessed their interaction with .

Results: Higher CAIDE scores were associated with an increased risk of dementia in Asian, Latinx, and NLW participants but not in Black participants.

Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants.

Introduction: We estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle-aged and older adults.

Methods: Among 45,616 dementia-free participants aged 45-80, linear regressions tested whether genetic risk score for AD (AD-GRS) had age-dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume.

Food Insecurity, Memory, and Dementia Among US Adults Aged 50 Years and Older.

Importance: Despite existing federal programs to increase access to food, food insecurity is common among US older adults. Food insecurity may affect Alzheimer disease and Alzheimer disease-related dementias via multiple mechanisms, yet there is almost no quantitative research evaluating this association.

Objective: To examine whether food insecurity in older adults is associated with later-life cognitive outcomes.

Snoring and risk of dementia: a prospective cohort and Mendelian randomization study.

Background: The association between snoring, a very common condition that increases with age, and dementia risk is controversial. Snoring is linked to obstructive sleep apnoea and cardiometabolic conditions, both of which are associated with an increased risk of dementia. However, snoring also increases with body mass index (BMI), which in late life is linked to lower dementia risk, possibly due to metabolic changes during prodromal dementia.

Olfactory Dysfunction and Depression Trajectories in Community-Dwelling Older Adults.

Background: We examined the relationship between baseline olfactory performance and incident significant depressive symptoms and longitudinal depression trajectories in well-functioning older adults. Inflammation and cognitive status were examined as potential mediators.

Methods: Older adults (n = 2 125, 71-82 years, 51% female, 37% Black) completed an odor identification task at Year 3 (our study baseline) of the Health, Aging, and Body Composition study.

Education, incident cancer, and rate of memory decline in a national sample of US adults in mid-to-later-life.

Introduction: Middle-aged and older adults who develop cancer experience memory loss following diagnosis, but memory decline in the years before and after cancer diagnosis is slower compared to their cancer-free counterparts. Educational attainment strongly predicts memory function during aging, but it is unclear whether education protects against memory loss related to cancer incidence or modifies long-term memory trajectories in middle-aged and older cancer survivors.

Materials And Methods: Data were from 14,449 adults (3,248 with incident cancer, excluding non-melanoma skin cancer) aged 50+ in the population-based US Health and Retirement Study from 1998 to 2016.

Alzheimer's Disease Genetic Risk, Cognition, and Brain Aging in Midlife.

We examined associations of an Alzheimer's disease (AD) Genetic Risk Score (AD-GRS) and midlife cognitive and neuroimaging outcomes in 1,252 middle-aged participants (311 with brain MRI). A higher AD-GRS based on 25 previously identified loci (excluding apolipoprotein E [APOE]) was associated with worse Montreal Cognitive Assessment (-0.14 standard deviation [SD] [95% confidence interval {CI}: -0.

Observational studies in Alzheimer disease: bridging preclinical studies and clinical trials.

Recent high-profile failures of Alzheimer disease treatments at the clinical trial stage have led to renewed efforts to identify and test novel interventions for Alzheimer disease and related dementias (ADRD). In this Perspective, we highlight the importance of including well-designed observational studies as part of these efforts. Observational research is an important cornerstone for gathering evidence on risk factors and causes of ADRD; this evidence can then be combined with data from preclinical studies and randomized controlled trials to inform the development of effective interventions.

Associations of dual sensory impairment with long-term depressive and anxiety symptoms in the United States.

Objective: We explored the associations of dual sensory impairment (DSI) with long-term depressive and anxiety symptoms as well as low perceived social support (LPSS) as a modifier of these associations.

Methods: Multinomial logistic regression models were used to examine the associations of DSI and single sensory impairment (hearing [pure-tone average > 25 dB] and vision [impaired visual acuity and/or contrast sensitivity]) with long-term depressive symptom (≥8 on the 10-item Center for Epidemiologic Studies-Depression Scale) and anxiety symptom (present on the Hopkins Symptom Checklist) latent classes from group-based trajectory models (rare/never; mild/moderate increasing; chronically high) among 2102 Health, Aging and Body Composition Study participants (mean age:74.0 ± 2.

Associations Between Handgrip Strength and Dementia Risk, Cognition, and Neuroimaging Outcomes in the UK Biobank Cohort Study.

Importance: The associations between muscle strength and cognitive outcomes have sparked interest in interventions that increase muscle strength for prevention of dementia, but the associations between muscle strength and cognitive aging are unclear, particularly among middle-aged adults.

Objective: To evaluate the association between handgrip strength (HGS) and dementia, reduced cognition, and poorer neuroimaging outcomes in a UK population of middle-aged adults.

Design, Setting, And Participants: This cohort study evaluated UK Biobank participants aged 39 to 73 years enrolled from 2006 to 2010 with measured HGS and prospectively followed up for dementia diagnosis.

Association of Genetic Variants Linked to Late-Onset Alzheimer Disease With Cognitive Test Performance by Midlife.

Importance: Identifying the youngest age when Alzheimer disease (AD) influences cognition and the earliest affected cognitive domains will improve understanding of the natural history of AD and approaches to early diagnosis.

Objective: To evaluate the age at which cognitive differences between individuals with higher compared with lower genetic risk of AD are first apparent and which cognitive assessments show the earliest difference.

Design, Setting, And Participants: This cross-sectional study used data from UK Biobank participants of European genetic ancestry, aged 40 years or older, who contributed genotypic and cognitive test data from January 1, 2006, to December 31, 2015.

Associations of dual sensory impairment with incident mobility and ADL difficulty.

Background: There is a dearth of studies examining the associations of objectively measured dual sensory impairment (DSI) with incident mobility and activities of daily life (ADL) difficulty longitudinally.

Methods: Cox proportional hazards models were used to examine the associations of DSI and single sensory impairment (hearing, vision) with incident mobility difficulty (many problems or inability to walk ¼ mile and/or climb 10 steps) and ADL difficulty up to six years of follow-up among 2020 participants of the Health, Aging, and Body Composition Study, a cohort of older adults aged 70-79 years from Pittsburgh, PA and Memphis, TN. Vision impairment (VI) was defined as impaired visual acuity (20/50 or worse on Bailey-Lovie distance test) and contrast sensitivity (<1.

Associations of Lower Extremity Peripheral Nerve Impairment and Risk of Dementia in Black and White Older Adults.

Background And Objectives: Peripheral nerve impairments and dementia are common among older adults and share risk factors. However, few studies have examined whether peripheral nerve function and dementia are associated. We evaluated whether lower extremity peripheral nerve impairments were associated with higher incidence of dementia and whether associations differed by comorbidity subgroups (diabetes, low vitamin B, and ε4 allele carriers).

Assessing bidirectional associations between cognitive impairment and late age-related macular degeneration in the Age-Related Eye Disease Study 2.

Introduction: We aimed to investigate bidirectional associations between cognitive impairment and late age-related macular degeneration (AMD).

Methods: Participants in the Age-Related Eye Disease Study 2 (AREDS2) received annual eye examinations and cognitive function testing (e.g.

Current Alzheimer disease research highlights: evidence for novel risk factors.

Alzheimer disease (AD) is the most common type of dementia characterized by the progressive cognitive and social decline. Clinical drug targets have heavily focused on the amyloid hypothesis, with amyloid beta (Aβ), and tau proteins as key pathophysiologic markers of AD. However, no effective treatment has been developed so far, which prompts researchers to focus on other aspects of AD beyond Aβ, and tau proteins.

Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline.

Background: Depressive symptoms may increase risk for dementia, but findings are controversial because late-life depression may be a prodromal dementia symptom. Life course data on depression and dementia risk may clarify this association; however, data is limited.

Objective: To impute adult depressive symptoms trajectories across adult life stages and estimate the association with cognitive impairment and decline.

Methods to Address Self-Selection and Reverse Causation in Studies of Neighborhood Environments and Brain Health.

Preliminary evidence suggests that neighborhood environments, such as socioeconomic disadvantage, pedestrian and physical activity infrastructure, and availability of neighborhood destinations (e.g., parks), may be associated with late-life cognitive functioning and risk of Alzheimer's disease and related disorders (ADRD).

Extension of Mendelian Randomization to Identify Earliest Manifestations of Alzheimer Disease: Association of Genetic Risk Score for Alzheimer Disease With Lower Body Mass Index by Age 50 Years.

Weight loss or lower body mass index (BMI) could be an early symptom of Alzheimer disease (AD), but when this begins to emerge is difficult to estimate with traditional observational data. In an extension of Mendelian randomization, we leveraged variation in genetic risk for late-onset AD risk to estimate the causal effect of AD on BMI and the earliest ages at which AD-related weight loss (or lower BMI as a proxy) occurs. We studied UK Biobank participants enrolled in 2006-2010, who were without dementia, aged 39-73, with European genetic ancestry.