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.

Cross-sectional data come from the Washington Heights-Inwood Columbia Aging Project (N = 778, 41% Hispanic, 33% non-Hispanic Black, 25% non-Hispanic White; 64% women). Magnetic resonance imaging (MRI) markers of BH included cortical thickness in Alzheimer’s disease signature regions and hippocampal, gray matter, and white matter hyperintensity volumes. CR was residual variance in an episodic memory composite after partialing out MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender and included potential mediators.

Marital status was associated with CR, but not BH. Compared to married individuals, those who were previously married (i.e., divorced, widowed, and separated) had lower CR than their married counterparts in the full sample, among White and Hispanic subgroups, and among women. Never married women also had lower CR than married women. These findings were independent of age, education, physical health, and household income. Among never married individuals, living with others was negatively linked to BH.

Marriage may protect late-life cognition via CR. Findings also highlight differential effects across race and ethnicity and sex/gender. Marital status could be considered when assessing the risk of cognitive impairment during routine screenings.

Women have a greater lifetime risk of developing Alzheimer’s disease (AD) dementia than men, a sex/gender disparity that cannot be explained by female longevity alone. There is substantial evidence for sex differences in the effects of APOE £4 on risk for AD. While APOE e4 increases AD risk in both sexes, women who carry APOE e4 are disproportionately vulnerable to cognitive impairment and AD compared to their counterpart men. In contrast to APOE e4, APOE £2 is associated with slower cognitive decline and a lower risk of AD. Although a less robust literature, APOE e2 may also have sex-specific effects. Because APOE e2 is the rarest major APOE allele, well-powered studies are needed to examine sex-specific effects. The objective of the present study was to examine sex-specific associations of APOE e2 carriage with longitudinal cognitive decline in a large cohort of clinically unimpaired adults.

We used observational data from two sources: the National Alzheimer’s Coordinating Center (NACC) and the Rush Alzheimer’s Disease Center (ROS/MAP/MARS) studies. We included data from clinically unimpaired adults who were >50 years old at baseline who self-identified as non-Hispanic White (NHW) or non-Hispanic Black (NHB). Participants were categorized as APOE £2, £4, or £3/e3 carriers. APOE e2/e4 carriers were excluded. The same battery of neuropsychological tests was used to assess global cognition in participants from both data sources. Linear mixed models examined interactive associations of genotype (£2 or £4 vs. £3/£3), sex, and time on longitudinal cognition in NHW and NHB participants separately. Analyses were first performed in a pooled sample of NACC and ROS/MAP/MARS participants and if significant they were repeated separately in each data source.

Across both data sources, 9,766 NHW (mean (SD) age=73.0(9.00) years, mean (SD) education=16.3(2.83) years, n(%) women=6,344(65.0)) and 2,010 NHB participants (mean(SD) age=71.3(7.59) years, mean(SD) education=14.9(3.10) years, n(%) women=1,583(78.8)) met inclusion criteria. Sex modified the association between APOE £2 and cognitive decline in NHW (ß=0.097, 95% CI: 0.023-0.172, pint=.01) but not NHB participants (ß=-0.011, 95% CI: -0.153-0.131, pint=.9). In sex-stratified analyses of NHW participants, APOE £2 (vs. £3/£3) carriage was associated with attenuated cognitive decline in men (ß=0.096, 95% CI: 0.037-0.155, p=.001), but not women (ß=-0.001, 95% CI: -0.044-0.043, p=.97). In analyses comparing men and women APOE £2 carriers, men exhibited slower cognitive decline than women (ß=0.120, 95% CI: 0.051-0.190, p=.001). Analyses performed separately in NACC and ROS/MAP revealed the same pattern of male-specific APOE £2 protection in NHW participants in both data sources.

In light of the longstanding view that APOE £2 protects against AD and dementia, our results provide evidence that APOE £2 is associated with attenuated cognitive decline in men but not women among NHW adults. This male-specific protection may contribute to sex differences in AD-related cognitive decline. Our findings have important implications for understanding the biological drivers of sex differences in AD risk, which is crucial for developing sex-specific strategies to prevent and treat AD dementia.

Historically, assessment of financial decision making (FDM) has largely relied on self- or informant-reports, and paper-and-pencil tests. However, subjective report is prone to under/over-estimation biases, and most available tests probe increasingly outdated tasks such as writing checks and checkbook management. Advances in technology have made online methods one of the most common and preferred styles of managing money. There is thus a critical need to develop modern and objective methods to assess financial decision making that can be used in clinical settings. The current study aimed to develop and validate a novel, simulated online money management (OMM) credit card task mimicking a real-world task.

Development. The OMM task was conceptualized based on collaborations with a diverse team of experts spanning neuropsychology, geriatrics, computer science, and economics. Administration. The task involves several sub-tasks including logging into a simulated credit card account, navigating a few pages to download a statement for a specific month, answering questions about where certain pieces of information are in the statement, identifying erroneous transactions in the account activity section, and answering questions involving practical aspects of managing a credit card. Pilot phase. Using an iterative process, the task was refined and piloted in ten participants. Validation. Performance was examined in relation to an existing online automated teller machine (ATM) task. Design & Setting. Cross-sectional, community-based prospective study.

OMM task. The newly developed OMM credit card task consists of two broad areas, (i) online navigation and (ii) content-focused (simple literacy, complex literacy, monitoring, awareness). ATM task. This measure consists of sequential tasks such as checking the balance in one’s account, transferring money between accounts, and withdrawing cash. Both the OMM and ATM tasks were administered remotely by a neuropsychologist using Zoom and Team Viewer on a Dell laptop.

Thirty-five cognitively healthy older adults were included with mean age=70.06 years (SD=3.82) and mean education=21.89 (SD=1.76). 72% were women, the majority were White (77%) while 20% were Black and 3% belonged to other races; 91% were non-Hispanic.

Bivariate correlations between the OMM task, ATM task and demographic variables were examined. Time and steps/clicks to complete the OMM task were the primary outcome metrics.

All participants were able to complete the OMM task. No significant associations were found between demographics (age, gender, education) and OMM metrics, and among OMM metrics (time and clicks). Significant associations in the expected direction were present between the OMM and ATM tasks. Time taken to answer the questions on the OMM task was associated with time required to complete the ATM task (r = 0.57, p < 0.001). Increased number of clicks on the OMM task was associated with increased number of errors (r = 0.54, p < 0.001) and increased time to complete the ATM task (r = 0.41, p = 0.01).

This is one of the first studies to develop and demonstrate the validity of a technologically based and practically relevant measure of financial decision making. Studies are ongoing to more comprehensively understand the psychometric properties of this novel task.

People whose parents had dementia or memory impairment are at higher risk for later-life cognitive impairment themselves. One goal of our research is to identify factors that either increase the risk of or protect against family history of dementia over the life course. External locus of control has been associated with lower cognitive function in middle-aged and older adults. Previous findings have shown that adults racialized as Black have relatively high levels of external locus of control due to inequity and racism. We hypothesized that lower parental memory would be associated with lower offspring memory among Non-Latinx Black and Non-Latinx White (hereafter Black and White, respectively) adults; and associations would be stronger among participants with higher levels of external locus of control.

Participants comprised 594 adults racialized as Black or White (60.3% Black; 62% women; aged 56.1 ± 10.4; 15.3 ± 2.7 years of education) from the Offspring Study who are the adult children of participants in the Washington Heights Inwood Columbia Aging Project (WHICAP). Parental memory was residualized for age (74.3 ± 6.0) and education (13.7 ± 3.1). Self-reported external locus of control was assessed using 8 items from the the perceived control questionnaire. Memory was assessed with the Selective Reminding Test, and a composite of total and delayed recall scores were computed. Linear regression quantified the interaction between parental memory and external locus of control on memory in models stratified by race, and adjusted for age, sex/gender, and number of chronic health diseases.

Among Black participants (n=358), there were no main effects of parental memory or locus of control on offspring memory. However, lower parental memory was associated with lower offspring memory among Black participants with high levels of external locus of control (standardized estimate=0.36, p=0.02, 95%CI [0.05, 0.67]). Associations were attenuated and non-significant at lower levels of control. Among White participants (n=236), there was a main effect of parental memory on offspring memory, and this association did not vary by levels of external locus of control.

Poor parental memory, which reflects risk for later-life cognitive impairment and dementia, was associated with lower memory performance among White middle-aged participants. Among Black participants, this association was observed among those with high levels of external locus of control only. Economic and social constraints shape levels of external locus of control and are disproportionately experienced by Black adults. In the face of greater external locus of control, a cascade of psychological and biological stress-related processes may be triggered and make Black adults’ memory function more vulnerable to the detrimental impact of parent-related dementia risk. Longitudinal analyses are needed to clarify temporal associations. Nonetheless, these findings suggest that reducing social and economic inequities disproportionately experienced by Black adults may dampen the effect of intergenerational transmission of dementia risk on cognition.

We assess the association between self-reported history of periodontal disease diagnosis with self-reported cognitive and functional decline at age ∼60. We also investigate (1) the roles of social background, demographic characteristics, education, and adolescent test scores in confounding that association and (2) the role of cardiovascular disease in mediating that association.

We use data from a nationally representative sample of 13,525 people who participated in the 2021 wave of the High School & Beyond (HSB) cohort study. HSB began in 1980 with a nationally-representative sample of American 10th and 12th grade students; these students have been followed up on six occasions since 1980, yielding extraordinary and prospectively-collected life course data on all key measures for a large, multicultural sample.

In 2021, HSB sample members were evaluated with neuropsychological tests that evaluated list learning and memory, semantic and letter fluency, and working memory. They were also asked to self-report memory and functional decline using the AD8, using a cutoff of 2 or more items for significant concerns. Mild Cognitive Impairment will be identified using an algorithm validated in a similar sample of middle aged participants.

Sample members were also asked in 2021 whether a medical professional had ever diagnosed them with periodontal disease; those responding affirmatively were then asked the years in which they started and stopped having periodontal disease.

Measures of social and economic background; demographic characteristics; and educational contexts, opportunities, and attainments were measured prospectively—and in great detail—in the surveys administered in the 1980s. Critically, almost all sample members completed a series of cognitive tasks during adolescence, allowing us to address a key set of confounders in the relationship between periodontal disease and MCI. Markers of cardiovascular disease were measured in both 2013 and 2021.

We estimate logistic regression models predicting significant cognitive and functional concerns as a function of periodontal disease history; we also estimate models that account for confounders, including social background, demographic characteristics, education, and cognitive skills during adolescence; finally, we estimate models that account for the mediating role of cardiovascular disease. All models account for the clustered sampling design of HSB and employ sampling weights to account for HSB’s complex sampling design and selective attrition from the panel.

About 15% of the cohort has been diagnosed with periodontal disease, and nearly one in five had significant cognitive and functional concerns.

People with a history of periodontal disease were more likely to report significant cognitive and functional concerns. This association remains substantive and statistically significant after adjusting for confounders. All else equal, the odds of people with a history of periodontal disease having an AD8 score of 2 or higher were about 60% greater than the odds of those not reporting periodontal disease. Very little of this association can be attributed to cardiovascular disease as a mediating pathway.

People with a history of periodontal disease are at greatly elevated risk of self-reported cognitive and functional concerns at age ∼60. This supports evidence— never before collected at this scale in a long-term, representative cohort study—that oral pathogens may contribute to cognitive well-being over the life course.

Socioeconomic disadvantage is a chronic stressor associated with several biological markers of health (e.g., inflammation) as well as early-onset cognitive aging. Studies examining socioeconomic status (SES) and its link with health outcomes exhibit no uniformity in the way in which SES is measured and defined. Also, studies have found that subjective socioeconomic status (SSES), defined by a subjective SES scale, was more consistently and strongly related to psychological functioning and health-related outcomes than objective socioeconomic status (OSES), defined by a composite score of education, household income, and occupation. The goal of the current study was to assess whether SSES mediates the relationship between OSES and neuropsychological test performance similarly across racial and ethnic groups.

Participants were 1,912 middle-aged older adults (13% non-Hispanic white, 17% non-Hispanic Black, 69% Hispanic/Latinx) from the Offspring study. Participants are the adult children of participants in the Washington Heights Inwood Columbia Aging Project, a community-based cohort study of aging and dementia representing the ethnic/racial diversity of upper Manhattan. Participants on average were 56.5 years of age and 67% were women. Measures of verbal learning and memory (SRT immediate and delayed recall), verbal fluency (animal and letter fluency), and attention/working memory (digit span forward and backward) were administered. OSES was characterized by years of formal education completed. SSES was measured by the MacArthur Scale of Subjective Social Status. The scale measures perceptions of one’s social standing relative to others. We conducted separate stratified mediation analyses for each neuropsychological outcome across each racial and ethnic group. All models were adjusted for age.

Participants with higher OSES demonstrated higher neuropsychological test scores (effect size associations ranged from .29 to .45) and reported higher SSES (b=.109 95% CI: .08, .14). Lower SSES was associated with lower neuropsychological test scores (effect-size range .06 to .13). In stratified analyses, the relationship between OSES and SSES was strongest for White participants (b=.13 [.01, .24]) compared with Latinx (b=.06 [.02, .11]) and Black (b=.06 [-.03, .16]) participants. Associations between SSES and neuropsychological outcomes were only reliable for White participants on SRT Immediate and Delayed Recall and Animal Fluency and for Black participants on Digit Span Forward. In mediation analyses, SSES mediated the relationship between OSES and Immediate Recall (indirect effect b=.18 [.001, .45]; 39% mediated), Delayed Recall (indirect effect b=.05 [.004, .09]; 44% mediated), and Animal Fluency (indirect effect b=.09 [.01, .20]; 22% mediated) for White participants. There was no evidence of mediation in Black or Latinx participants.

The relationship between OSES and SSES was strongest for White participants compared to Black and Latinx participants. Even though perception of social status predicted lower cognitive test scores among Black and Latinx adults, it is only a part of the indirect pathway linking OSES to cognitive function among White adults. It is likely that mechanisms related to tangible resources that benefit health (as opposed to perceived inequity) are in the pathway linking education to cognition among Black and Latinx, and thus intervening on systems of inequality throughout the life course has the most promise for improving brain health in those communities.

The AD8 is a validated screening instrument for functional changes that may be caused by cognitive decline and dementia. It is frequently used in clinics and research studies because it is short and easy to administer, with a cut off score of 2 out of 8 items recommended to maximize sensitivity and specificity. This cutoff assumes that all 8 items provide equivalent “information” about everyday functioning. In this study, we used item response theory (IRT) to test this assumption. To determine the relevance of this measure of everyday functioning in men and women, and across race, ethnicity, and education, we conducted differential item functioning (DIF) analysis to test for item bias.

Data came from the 2021 follow up of the High School & Beyond cohort (N=8,690; mean age 57.5 ± 1.2; 55% women), a nationally representative, longitudinal study of Americans who were first surveyed in 1980 when they were in the 10th or 12th grade. Participants were asked AD8 questions about their own functioning via phone or internet survey. First, we estimated a one-parameter (i.e., differing difficulty, equal discrimination across items) and two-parameter IRT model (i.e., differing difficulty and differing discrimination across items). We compared model fit using a likelihood-ratio test. Second, we tested for uniform and non-uniform DIF on AD8 items by sex, race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), education level (high school or less, some college, BA degree or more), and survey mode (phone or internet). We examined DIF salience by comparing the difference between original and DIF-adjusted AD8 scores to the standard error of measurement of the original score.

The two-parameter IRT model fit the data significantly better than the one-parameter model, indicating that some items were more strongly related to underlying everyday functional ability than others. For example, the “problems with judgment” item had higher discrimination (more information) than the “less interest in hobbies/activities” item. There were significant differences in item endorsement by race/ethnicity, education, and survey mode. We found significant uniform and non-uniform DIF on several items across each of these groups. For example, for a given level of functional decline (theta) White participants were more likely to endorse “Daily problems with thinking/memory” than Black and Hispanic participants. The DIF was salient (i.e., caused AD8 scores to change by greater than the standard error of measurement for a large portion of respondents) for those with a college degree and phone respondents.

In a population representative sample of Americans ∼age 57, the items on the AD8 contributed differing levels of discrimination along the range of everyday functioning that is impacted by later life cognitive impairment. This suggests that a simple cut-off or summed score may not be appropriate since some items yield more information about the underlying construct than others. Furthermore, we observed significant and salient DIF on several items by education and survey mode, AD8 scores should not be compared across education groups and assessment modes without adjustment for this measurement bias.

Previous research established that white matter hyperintensities (WMH), a biomarker of small vessel cerebrovascular disease, are strong predictors of cognitive function in older adults and associated with clinical presentation of Alzheimer’s disease (AD), particularly when distributed in posterior brain regions. Secondary prevention clinical trials, such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, target amyloid accumulation in asymptomatic amyloid positive individuals, but it is unclear the extent to which small vessel cerebrovascular disease accounts for performance on the primary cognitive outcomes in these trials. The purpose of this study was to examine the relationship between regional WMH volume and performance on the Preclinical Alzheimer Cognitive Composite (PACC) among participants screened for participation in the A4 trial. We also determined whether the association between WMH and cognition is moderated by amyloid positivity status.

We assessed demographic, amyloid PET status, cognitive screening, and raw MRI data for participants in the A4 trial and quantitated regional (by cerebral lobe) WMH volumes from T2-weighted FLAIR in amyloid positive and amyloid negative participants at screening. Cognition was assessed using PACC scores, a z-score sum of four cognitive tests: The Mini-Mental State Examination (MMSE), the Free and Cued Selective Reminding Test, Logical Memory Test, and Digit Symbol Substitution Test. We included 1329 amyloid positive and 329 amyloid negative individuals (981 women; mean age=71.79 years; mean education=16.58 years) at the time of the analysis. The sample included Latinx (n=50; 3%), non-Latinx (n=1590; 95.9%), or unspecified ethnicity (n=18; 1.1%) individuals who identified as American Indian/Alaskan Native (n=7; 0.4%), Asian (n=38; 2.3%), Black/African American (n=41; 2.5%), White (n=1551 ; 93.5%), or unspecified (n=21; 1.3%) race. We first examined the associations of total and regional WMH volume and amyloid positivity on PACC scores (the primary cognitive outcome measure for A4) using separate general linear models and then determined whether amyloid positivity status and regional WMH statistically interacted for those WMH regions that showed significant main effects.

Both increased WMH, in the frontal and parietal lobes particularly, and amyloid positivity were independently associated with poorer performance on the PACC, with similar magnitude. In subsequent models, WMH volume did not interact with amyloid positivity status on PACC scores.

Regionally distributed WMH are independently associated with cognitive functioning in typical participants enrolled in a secondary prevention clinical trial for AD. These effects are of similar magnitude to the effects of amyloid positivity on cognition, highlighting the extent to which small vessel cerebrovascular disease potentially drives AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered explicitly when evaluating outcomes in trials, both as potential effect modifiers and as possible targets for intervention or prevention. The findings from this study cannot be generalized widely, as the participants are not representative of the overall population.

Neuropsychiatric symptoms concerning mood are common in Alzheimer's disease (AD), but it is unclear if they are etiologically related to AD pathophysiology or due to factors considered to be non-pathogenic, such as small vessel cerebrovascular disease. New generation clinical trials for AD often enroll participants with evidence of AD pathophysiology, indexed by amyloid PET scanning, but who are cognitively asymptomatic. We used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study to examine the extent to which depressive symptoms are associated with amyloid pathophysiology and small vessel cerebrovascular disease, in the form of white matter hyperintensities (WMH).

The A4 study randomizes cognitively healthy older adults with evidence of amyloid pathophysiology on PET scanning. We used screening data, which included amyloid status (positive, negative) by visual read, amyloid PET standard uptake value ratio (SUVR) in cortical regions, and MRI data acquired in a subset (n=1,197, mean age 71.6 +/- 4.8 years, 57% women) to quantitate total WMH volume. Depressive symptoms were evaluated with the 15-item Geriatric Depression Scale, which we used both as a continuous variable and to define 'depressed' and 'non-depressed' groups, based on a cut score of > 5. We examined whether 1) depressive symptoms and proportion of depressed individuals differed between amyloid positive and negative groups, 2) there is a relationship between amyloid SUVR and depressive symptoms that differs as a function of amyloid positivity status, and 3) there is a relationship between WMH volume and depressive symptoms that differs as a function of amyloid positivity status.

Although depressive symptom severity did not differ between groups (t=0.14, p=0.88), a greater proportion of individuals were classified as depressed in the amyloid negative group than the amyloid positive group (3.5% vs. 1.9%, X2=4.60, p=0.032). Increased amyloid SUVR was associated with increased GDS scores among amyloid positive individuals (r=0.117, p=0.002) but not among amyloid negative individuals (r=0.006, p=0.68, Positivity Status x SUVR interaction on GDS: ß=0.817, p=0.029). Increased WMH was associated with higher GDS scores (ß=0.105, p=0.017) but not differentially in amyloid positive and negative participants (Positivity Status x WMH interaction on GDS: ß=-0.010, p=0.243).

These analyses have several implications. First, individuals who are screened to participate in a clinical trial but do not have evidence of amyloidosis may be misattributing concerns about underlying AD pathophysiology to depressive symptoms. Second, the severity of AD pathophysiology, indexed by amyloid PET SUVR, may drive a small increase in depressive symptomatology among individuals over visual diagnostic thresholds. Third, small vessel cerebrovascular changes are additionally associated with depressive symptoms but in a manner that is independent of AD pathophysiology. Overall, depressive symptoms and depression are likely multiply determined among prospective clinical trial participants for preclinical AD.

Alzheimer’s disease (AD) pathophysiology, including β-amyloid (Aβ), can be appreciated with molecular PET imaging. Among older adults, the distribution of Aβ standard uptake value ratios (SUVR) is typically bimodal and a diagnostic cut is applied to define those who are amyloid ‘positive’ and ‘negative’. However, it is unclear whether the dynamic range of SUVRs in amyloid positive and negative individuals is meaningful and associated with cognition. Previous work by Insel and colleagues (2020) used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) trial to demonstrate subtle associations between a cortical summary SUVR and cognition, particularly on the Free and Cued Selective Reminding Test (FCSRT). We followed up this study to determine the extent to which regional SUVR is associated with performance on the FCSRT in amyloid positive and negative participants screened for participation in the A4 study.

We accessed regional Aβ SUVR, including anterior cingulate, posterior cingulate, parietal, precuneus, temporal, and medial/orbital frontal regions, along with FCSRT15 and demographic data from 4492 A4 participants at screening. Participants were coded as amyloid positive (n=1329; 30%) or amyloid negative (n=3169; 70%) based on a summary SUVR of greater than or equal to 1.15. We used separate general linear models to examine the association of total or regional SUVR, amyloid positivity status, and the interaction of SUVR and amyloid status with FCSRT scores. We compared model fits across regions with the Akaike Information Criterion (AIC). We ran post hoc correlational analyses examining the relationship between SUVR and FCSRT scores stratified by amyloid status in the case of significant interactions. Results were similar with and without demographic adjustment.

There was a significant interaction of summary and all regional SUVR with FCSRT scores in addition to main effects of amyloid positivity. In all models, there were small negative associations between SUVR and memory in amyloid positive individuals. For amyloid negative individuals, there was a significant and very small negative association between SUVR and FCSRT scores only in the parietal lobes and precuneus regions. Model fits were generally similar across the different analyses.

In this sample of individuals screened for a secondary prevention trial of AD, there were consistent associations between Aβ SUVR in all regions and memory for those considered amyloid positive. However, for individuals considered amyloid negative, there were only very small associations between SUVR and memory in parietal and precuneus regions. We conclude that the dynamic range of amyloid may be relevant among those with diagnostic evidence of amyloidosis, but that subtle Aβ accumulation in posterior regions may relate to declining memory in “subthreshold” states.

White matter hyperintensities (WMH) are a radiological marker of small vessel cerebrovascular disease that are related to cognition and memory decline in aging and Alzheimer’s disease (AD). However, the mechanisms that link WMH to memory impairment and whether they interact with or act independently of AD pathophysiology are unclear. The transentorhinal cortex (BA35) is among the earliest anatomical regions to show tau deposition and subsequent atrophy, and baseline posterior WMH is related to longitudinal cortical thinning of the entorhinal cortex. However, it is unclear whether regional WMH are related to BA35 volume specifically, and whether this relationship is influenced by amyloid-β (Aβ) burden. We hypothesized that WMH in the vascular territory of the posterior cerebral artery (PCA), which perfuses both posterior and medial temporal lobe regions, would be associated with reduced BA35 volume and with lower memory in older adults independently of Aβ.

114 older adults without dementia, aged 60 to 98 years (mean (SD) = 78.31 (11.02), 71 (62.8%) women), were included. Regional WMH volumes were derived from T2-FLAIR images using ANTs, a vascular territory atlas and manual editing. Global Aβ was assessed with 18F-florbetapir PET, using SUVR of a cortical composite region (FBP mean SUVR) with a cerebellar reference region. Total transentorhinal (BA35) volume was derived using T1 and T2-weighted images using ASHS. To assess hippocampal pattern separation ability, an index of episodic memory, participants completed both object (MDT-O) and spatial (MDT-S) versions of a mnemonic discrimination task, with the lure discrimination index as the outcome. Using linear regressions, we first tested for associations among PCA-defined WMH, Aβ, BA35 volume, and MDT-S and MDT-O scores. We then tested whether the relationship between PCA-defined WMH and MDT-O performance was mediated by BA35 volume and whether this mediation was moderated by Aβ. All models adjusted for age, sex, and education.

PCA-defined WMH were related to higher FBP mean SUVR (b=0.287, p=0.042) and lower BA35 volume (b=-0.222, p=0.038). PCA-defined WMH were also negatively related to MDT-O performance (b=-0.229, p=0.044), but not to MDT-S (b=-0.171, p=0.118). FBP mean SUVR was not related to BA35 volume (b=-0.131, p=0.344) or MDT performance (MDT-S: b=-0.138, p=0.348; MDT-O: b=0.059, p=0.690). Furthermore, FBP mean SUVR did not interact with PCA-defined WMH to predict memory performance (interaction b=-0.039, p=0.973), nor BA35 volume (interaction b=-0.140, p=0.894). The association of PCA-defined WMH to MDT-O was fully mediated by BA35 volume (indirect effect b=-0.0005, 95% CI (-0.0014, -0.0003)). This mediation was not moderated by FBP mean SUVR (indirect effect b=-0.00001, 95% CI (-0.001, 0.001)).

We found that PCA-defined WMH were related to memory performance in older adults, and this association is fully mediated by transentorhinal volume. While PCA-defined WMH are related to higher global Aβ burden, there is no interaction between PCA-defined WMH and Aβ on BA35 volume. These findings point to an amyloid-independent vascular pathway towards memory decline in aging and AD. Future work should examine whether the pathway linking PCA-defined WMH to transentorhinal cortex atrophy and subsequent memory decline is mediated by regional tau pathology.

The current research framework recommends using biomarkers to further understand Alzheimer’s disease (AD) pathogenesis, including other contributing factors like cerebrovascular disease. In longitudinal studies of people with neuropathological examination after death, baseline loneliness was associated with lower cognition, faster cognitive decline, and future AD risk, independent of AD pathology. Examination of memory impairment along with AD and cerebrovascular biomarkers, could aid risk reduction efforts earlier in the lifecourse and among populations with more exposure to loneliness. We hypothesized that loneliness is associated with amyloid, vascular, and neurodegeneration biomarkers; with worse memory; and that loneliness increases the susceptibility to biomarker-related memory impairment.

A subset of cognitively unimpaired older adults with available amyloid PET, vascular MRI (white matter hyperintensity volume, WMH), structural MRI (cortical thickness in AD signature regions), neuropsychological testing (memory factor score), dichotomized loneliness data (one item from CES-D), and relevant medical data were drawn from the community-based Washington Heights-Inwood Columbia Aging Project (WHICAP; n=169; covariates included age=81±6 years; 63% women; 49/31/20% Non-Hispanic Black/Non-Hispanic White/Hispanic; education=13±4 years; 32% APOE-e4 carriers). General linear models in the overall sample and stratified by race and ethnicity tested the association between loneliness and AD and cerebrovascular biomarkers, loneliness and memory, and the interaction of loneliness and biomarkers on memory, adjusting for covariates.

Loneliness was endorsed in 18% of participants, marginally associated with older age (2.1 [-0.2, 4.4], p=0.08), was more likely in those with untreated diabetes (13/0.1% lonely/not lonely, p=0.001), associated with lower cortical thickness (-0.05 [-0.09, -0.02], p=0.01), and associated with lower memory (0.3 [-0.6, -0.001], p=0.05). In Non-Hispanic White participants, loneliness was associated with greater WMH volume (0.5 [0.07, 0.82], p=0.03), while in Hispanic participants, loneliness was associated with lower cortical thickness (-0.16 [-0.24, -0.08], p=0.0006). In Non-Hispanic Black participants, loneliness was associated with lower memory (-13 [-26, -0.5], p=0.05), and the association between lower cortical thickness and lower memory was stronger in those that endorse loneliness (5 [0.2, 10], p=0.05). In Hispanic participants, loneliness was associated with higher memory (13 [4, 22], p=0.009), but the association between higher amyloid burden and lower memory was stronger in those that endorse loneliness (-12 [-20, -4], p=0.006); further, loneliness was marginally associated with lower memory (-0.7 [-1.4, 0.1], p=0.09), independently of WMH.

Associations between loneliness and biomarkers may relate to health seeking behavior, reported as treatment status for diabetes, for cerebrovascular burden and general neurodegeneration, but might be more complex for amyloid. The degree to which loneliness increased the susceptibility to amyloid and neurodegeneration-related, but not cerebrovascular-related, memory impairment, specifically, may suggest that domains beyond memory should be considered. Future work should be longitudinal to disentangle the effects of loneliness from related constructs like depression and anxiety, incorporate other AD biomarkers such as hyperphosphorylated tau, and incorporate biological mechanisms (e.g., stress, inflammation) into models of loneliness and AD pathogenesis. Older adults from all backgrounds may be more susceptible to loneliness, which was associated with lower memory; culturally-humble, social support-based interventions may reduce the risk of cognitive impairment.

Non-Hispanic Black older adults experience a disproportionate burden of Alzheimer’s Disease and related dementias (ADRD) risk compared to non-Hispanic White older adults. It is necessary to identify mechanisms that may be contributing to inequities in cognitive aging. Psychosocial stressors that disproportionately affect Black adults (e.g., discrimination) have the potential to impact brain health through stress pathways. The brain’s white matter, which appears to be particularly important for ADRD risk among Black older adults, may be uniquely vulnerable to stress-related physiological dysfunction. To further understand whether and how discrimination can affect ADRD risk, this study aimed to examine associations between multiple forms of racial discrimination and white matter integrity, operationalized through diffusion tensor imaging.

Cross-sectional data were obtained from 190 non-Hispanic Black residents aged 65+ without dementia in northern Manhattan. Racial discrimination was self-reported using the Everyday Discrimination and Major Experiences of Lifetime Discrimination scales. Example items from the Everyday Discrimination Scale include: “You are treated with less respect than other people”; “You are called names or insulted.” Example items from the Major Experiences of Lifetime Discrimination Scale include: “At any time in your life, have you ever been unfairly fired from a job?”; “Have you ever been unfairly denied a bank loan?” Racial discrimination was operationalized as experiences attributed to “race” or “skin color.” White matter integrity was assessed using fractional anisotropy (FA) via diffusion tensor imaging. Multivariable regression models evaluated the unique effects of everyday and major experiences of lifetime racial discrimination on mean FA in the whole brain and specific regions. Initial models controlled for age, sex/gender, intracranial volume, and white matter hyperintensities. Subsequent models additionally controlled for socioeconomic and health factors to consider potential confounders or mediators of the relationship between discrimination and white matter integrity.

Major experiences of lifetime discrimination were negatively associated with mean FA within the left cingulum cingulate gyrus and the right inferior fronto-occipital fasciculus. These associations persisted when controlling for additional covariates (i.e., education, depression, and cardiovascular diseases). In contrast, major experiences of lifetime discrimination were positively associated with mean FA within the right superior longitudinal fasciculus (temporal part). This association was attenuated when controlling for additional covariates. Everyday racial discrimination was not associated with mean FA in any regions.

These results extend prior work linking racial discrimination to brain health and provide evidence for both risk and resilience among Black older adults. Major experiences of lifetime racial discrimination, a proxy for institutional racism, may have a stronger effect on white matter integrity than everyday racial discrimination, a proxy for interpersonal racism. Educational opportunities and cardiovascular risk factors may represent mediators between racial discrimination and white matter integrity. White matter integrity within specific brain regions may be a mechanism through which racially patterned social stressors contribute to racial disparities in ADRD. Future research should characterize within-group heterogeneity in order to identify factors that promote resilience among Black older adults.

We ask about the degree to which the association between (1) the quantity and quality of people’s education and (2) midlife self-reported concerns about cognition and daily function is mediated by occupational complexity. The overarching hypothesis is that amount and quality of education provides people with access to better jobs, including jobs that are more cognitively complex. Occupational complexity, in turn, may be protective against cognitive impairment. If true, this means that part of the poorly-understood connection between education and cognitive impairment can be attributed to occupational complexity.

We use data from a nationally representative sample of 13,525 people who participated in the 2021 wave of the High School & Beyond (HSB) cohort study. HSB began in 1980 with a nationally-representative sample of American 10th and 12th grade students; these students have been followed up on six occasions since 1980, yielding extraordinary and prospectively-collected life course data on all key measures for a large, multicultural sample.

In 2021, HSB sample members were evaluated with neuropsychological tests that evaluated list learning and memory, semantic and letter fluency, and working memory. They were also asked to self-report memory and functional decline using the AD8, using a cutoff of 2 or more items for significant concerns. Mild Cognitive Impairment will be identified using an algorithm validated in a similar sample of middle aged participants.

HSB surveys gathered information about sample members’ labor force activities in every survey between 1980 and 2021, including information sufficient to code verbatim reports of occupations to the standards of the 2010 Standard Occupational Classification. We have linked these codes for sample members’ 2013 and 2021 occupations to the O*Net database, which includes extensive information about the cognitive complexity (and other attributes) of every occupation.

Measures of key confounders—including social and economic background; demographic characteristics; educational contexts, opportunities, and attainments that are associated with labor force outcomes; adolescent achievement test scores; and aspects of midlife occupations besides complexity (e.g., how well they pay)—were measured prospectively and in great detail in the surveys administered between the 1980s and 2021.

We estimate logistic regression models predicting significant cognitive and functional concerns as a function of educational contexts, opportunities, and outcomes; we also estimate models that account for the confounders listed above. Our main focus is on coefficients for education in models that do and do not include occupational complexity as a mediator. All models account for the clustered sampling design of HSB and use sampling weights to account for HSB’s complex sampling design and selective attrition from the panel.

Nearly one in five cohort members had significant cognitive and functional concerns; rates are lower for non-Latinx Whites and for better educated people. Associations between educational contexts, opportunities, and outcomes (including attainment) are robust, even after adjusting for confounders.

Between one quarter and one third of the conditional association between education and self-reported cognitive and functional concerns can be attributed to occupational complexity.

Occupational complexity is an important pathway through which more and better education protects people from concerns about cognitive and functional decline at about age 60.

Code-switching is when bilingual individuals alternate between two languages in the same conversation. Some studies find that code-switching frequency is associated with executive functioning, while others do not. Individual attitudes towards bilingual language use and code-switching may explain the inconsistency in the literature. For instance, greater positive attitudes towards code-switching may be associated with more likelihood to engage in that practice and thus strengthen the cognitive benefit in executive function. Additionally, code-switching between English and Spanish has been stigmatized in the U.S., therefore it is unclear what sociocultural factors may predict positive attitudes. In this study, we assessed Latinx bilinguals’ attitudes on code-switching and investigated their relationship with code-switching frequency, sociodemographic and linguistic factors, and executive functioning.

Participants were 525 community-dwelling English-Spanish bilingual Latinx adults from the Offspring study (Mage= 55.38 (10.42); Meducation= 12.62 (3.34); 71% women; 41% tested in English, 75% immigrant). A language history questionnaire assessed for bilingualism and code-switching frequency. Participants completed 7 questions on code-switching attitudes on a 7-point Likert scale ranging from Strongly Disagree to Strongly Agree (e.g., “switching between languages in a conversation is an important part of my identity”), that were summed for a total score with higher scores indicating more positive attitudes. Executive functioning was assessed with the NIH Toolbox Cognition battery, verbal fluencies, and the digit span test. Sociodemographic and linguistic factors included age, sex, education, immigrant status, parental years of education, English and Spanish proficiency (average score on self-reported ratings on speaking, reading, writing, and understanding), and testing language. General linear models evaluated the association of code-switching attitudes on executive function, after adjusting for relevant covariates.

Positive code-switching attitudes were correlated with greater code-switching, r(499)=.33, p<.001. Younger age r(499)=-.11, being born in the US t(493)=-2.05, greater English proficiency r(497)=.15, and English dominance t(499)=2.22, were associated with more positive code-switching attitudes (all p’s <.05). Sex, education, parental years of education, and Spanish proficiency were not associated with code-switching attitudes. Overall models of attitudes with executive function indicated that positive code-switching attitudes were associated with worse visual working memory (b = -0.08, t(169) = -2.75, 95% CI [0.14, -0.02]) after adjusting for age, sex, education, immigration status, parental years of education and testing language. Code-switching attitudes were not significantly associated with other executive function measures.

Among a community-based sample of bilingual middle-aged Latinx adults, positive attitudes towards code-switching were associated with greater likelihood of code-switching in conversations, higher English proficiency, being US born, younger age, and English language dominance but negatively associated with visual working memory. These findings indicate that code-switching attitudes are influenced by sociodemographic and linguistic factors. Additionally, the negative association between code-switching attitudes and visual working memory provides support for previous studies showing code-switching as a disadvantage to cognition. Results of this study suggest that detailed characterization of sociocultural factors and aspects of bilingualism can provide further clarity in determining if there is a potential bilingual cognitive advantage. Future research should examine the relationship of code-switching with other aspects of bilingualism (e.g., age of acquisition).

Higher education is strongly associated with better cognitive function in older adults. Previous research has also showed that positive psychosocial factors, such as selfefficacy and emotional and instrumental support, are beneficial for late-life cognition. There is prior evidence of a buffering effect of self-efficacy on the relationship between educational disadvantage and poor cognition in older adults, however it is not known if other psychosocial factors modify the schooling-cognition relationship. We hypothesized that higher levels of emotional and instrumental support will diminish the association between lower education and lower cognitive test scores among older adults.

553 older adults without dementia (42.1% non-Latinx Black, 32.2% non-Latinx White, 25.7% Latinx; 63.2% women; average age 74.4 (SD 4.3)) from the Washington Heights-Inwood Columbia Aging Project. Neuropsychological tests assessed four cognitive domains (language, memory, psychomotor processing speed, and visuospatial function). Self-reported emotional and instrumental support were assessed with measures from NIH Toolbox. Linear regression estimated interactions between education and the two support measures on cognition in models stratified by cognitive domain and racial and ethnic group. Covariates included age, sex/gender, and chronic health conditions (e.g. heart disease, stroke, cancer, etc.).

Education was associated with cognition across racial and ethnic groups. For every one year of schooling, the processing speed z-score composite was 0.33 higher among Latinx participants, 0.10 among non-Latinx Black participants, and 0.03 higher among non-Latinx White participants. The education-cognition relationship was generally similar across cognitive domains with larger effects in non-Latinx Black and Latinx participants than in White participants. Low education was associated with slower processing speed among Black participants with low emotional support (B = 0.224, 95% CI [0.014, 0.096]), but there was no association between low education and processing speed among Black older adults with high levels of emotional support (beta for interaction = -.142, 95% CI [-0.061, -0.001]). A similar pattern of results was observed for instrumental support (beta for interaction = -.207, 95% CI [-0.064, 0.010]). There were no interactions between support and education on other cognitive domains or among Latinx and White participants.

We found that higher levels of emotional and instrumental support attenuate the detrimental effect of educational disadvantages on processing speed in older Black adults. This may occur via benefits of social capital, which provides access to health resources and knowledge, increased social interaction, an emotional outlet allowing the ability to better cope with stress. Longitudinal analyses are needed to examine temporal patterns of associations. In addition, improving equitable access to high quality schools will improve later-life cognitive outcomes for future generations of older adults. However, for the growing number of Black older adults who will not experience the benefits of structural improvements in the education system, emotional and instrumental support may represent a modifiable psychosocial factor to reduce their disproportionate burden of cognitive morbidity.

Neuropsychology is in a nascent stage of understanding the mechanisms that link social forces, psychosocial experiences, and brain health. Discrimination is associated with lower quality of life, higher stress, and worse physical health outcomes in Latinx, but contradictory findings in prior research complicate our understanding of its relationship to cognition. These contradictory results may be explained by heterogeneity within the broad category of Latinx, a cultural identity that requires more nuanced conceptualization. Immigration status is a primary social identifier for Latinx people that carries significant stigma. However, prior research found enculturation promotes better physical and mental health outcomes in immigrants compared to their US-born counterparts, which may protect immigrant Latinx from the cognitive costs of discrimination. The current study hypothesized that the effect of discrimination on cognition will be stronger in US-born Latinx compared to immigrant Latinx.

We partnered with 1,023 neurologically healthy, community dwelling Latinx adults (M age=56.1(±10.7); M education=12.5(±3.7); 69% women) in a prospective cohort study in NYC investigating risks factors for Alzheimer’s disease. Immigration status was determined by self-report of birthplace. Measures of attention, language, and memory were administered by bilingual examiners in the participants’ self-selected preferred language of English (n = 388) or Spanish (n=635). Discrimination, measured with the Everyday Discrimination Scale and Major Experiences of Discrimination Scale, was chronicity coded to weigh experiences of discrimination according to yearly chronicity. Linear regression models were employed for US-born and immigrant participants to assess the relationship between both discrimination measures and each cognitive measure.

Compared to US-born Latinx (n = 224), immigrant Latinx (n = 799; primarily from the Dominican Republic) were older, had fewer years of school, had lower income, and were much more likely to have chosen to be assessed in Spanish. Immigrants reported experiencing significantly fewer everyday and major experiences of discrimination than nonimmigrants. In unadjusted models, discrimination did not predict cognitive performance among US-born Latinx. Among immigrant Latinx, more major experiences of discrimination across the lifetime predicted better phonemic (F(2,362) = 4.167, p<0.05, R2=0.017) and semantic fluency (F(2,362) = 3.304, p<0.05, R2=0.013) but was not associated with measures of attention or memory.

Discrimination is an important life stressor for Latinx people living in the US, particularly when its impact is summed across intersectional identities. The current study is among the first to explore the potential cognitive impact of discrimination within a group of Latinx adults. The described relationship between discrimination and language performance in this cohort may be confounded by the language in which cognitive tests were administered. Future studies should consider how discrimination measures may be limited in their ability to accurately capture the experiences of US-born and immigrant Latinx groups and expand the measurement of cognition to additional domains.

Stress is a risk factor for numerous negative health outcomes, including cognitive impairment in late-life. The negative association between stress and cognition may be mediated by depressive symptoms, which separate studies have identified as both a consequence of perceived stress and a risk factor for cognitive decline. Pathways linking perceived stress, depressive symptoms, and cognition may be moderated by sociodemographics and psychosocial resources. The goal of this cross-sectional study was to identify modifying factors and enhance understanding of the mechanisms underlying the stress–cognition association in a racially and ethnically diverse sample of older adults.

A linear regression estimated the association between perceived stress and episodic memory in 578 older adults (Mage = 74.58) in the Washington Heights-Inwood Columbia Aging Project. Subsequent models tested whether depressive symptoms mediated the stress–memory relationship and whether sociodemographics (gender, race, and ethnicity) or perceived control moderated these pathways.

Independent of sociodemographics and chronic diseases, greater perceived stress was associated with worse episodic memory. This relationship was mediated by more depressive symptoms. Higher perceived control buffered the association between stress and depressive symptoms. There was no significant moderation by gender, race, or ethnicity.

Depressive symptoms may play a role in the negative association between perceived stress and cognition among older adults; however, longitudinal analyses and studies using experimental designs are needed. Perceived control is a modifiable psychological resource that may offset the negative impact of stress.

Previous cross-sectional studies have documented associations between positive psychosocial factors, such as self-efficacy and emotional support, and late-life cognition. Further, the magnitudes of concurrent associations may differ across racial and ethnic groups that differ in Alzheimer’s disease risk. The goals of this longitudinal study were to characterize prospective associations between positive psychosocial factors and cognitive decline and explicitly test for differential impact across race and ethnicity.

578 older adults (42% non-Hispanic Black, 31% non-Hispanic White, and 28% Hispanic) in the Washington Heights-Inwood Columbia Aging Project completed cognitive and psychosocial measures from the NIH Toolbox and standard neuropsychological tests over 2.4 years. Latent difference scores were used to model associations between positive psychosocial factors and cognitive decline controlling for baseline cognition, sociodemographics, depressive symptoms, physical health, and other positive psychosocial factors. Multiple-group modeling was used to test interactions between the positive psychosocial factors and race/ethnicity.

Higher NIH Toolbox Friendship scores predicted less episodic memory decline. One standard deviation increase in friendship corresponded to 6 fewer years of memory aging. This association did not significantly differ across racial/ethnic groups.

This longitudinal study provides support for the potential importance of friendships for subsequent episodic memory trajectories among older adults from three ethnic groups. Further study into culturally informed interventions is needed to investigate whether and how friend networks may be targeted to promote cognitive health in late life.

To determine the effect of three psycholinguistic variables—lexical frequency, age of acquisition (AoA), and neighborhood density (ND)—on lexical-semantic processing in individuals with non-fluent (nfvPPA), logopenic (lvPPA), and semantic primary progressive aphasia (svPPA). Identifying the scope and independence of these features can provide valuable information about the organization of words in our mind and brain.

We administered a lexical decision task—with words carefully selected to permit distinguishing lexical frequency, AoA, and orthographic ND effects—to 41 individuals with PPA (13 nfvPPA, 14 lvPPA, 14 svPPA) and 25 controls.

Of the psycholinguistic variables studied, lexical frequency had the largest influence on lexical-semantic processing, but AoA and ND also played an independent role. The results reflect a brain-language relationship with different proportional effects of frequency, AoA, and ND in the PPA variants, in a pattern that is consistent with the organization of the mental lexicon. Individuals with nfvPPA and lvPPA experienced an ND effect consistent with the role of inferior frontal and temporoparietal regions in lexical analysis and word form processing. By contrast, individuals with svPPA experienced an AoA effect consistent with the role of the anterior temporal lobe in semantic processing.

The findings are in line with a hierarchical mental lexicon structure with a conceptual (semantic) and a lexeme (word-form) level, such that a selective deficit at one of these levels of the mental lexicon manifests differently in lexical-semantic processing performance, consistent with the affected language-specific brain region in each PPA variant.