Despite significant recent advances in test development in research settings, neuropsychological tests and normative data used in clinical settings have fallen behind in innovation in terms of empiricism and modality of administration (Bilder & Reise, 2019). Most widely-used test paradigms were initially developed 50-150 years ago with normative data that is often limited to White American-born monolingual English samples (Pugh et al., 2022; Rabin et al., 2016). Few digital tests have successfully translated into clinical use (Collins & Riley, 2016).

Mayo Test Development through Rapid Iteration, Validation, and Expansion (Mayo Test Drive) is a remote platform for neuropsychological test development and self-administration that is accessible through any web-based device (Stricker et al., 2022). To date, we have demonstrated rapid validation and clinical translation of the SLS in native English speaking older adults and are now beginning cultural/linguistic adaptation for further validation, and clinical translation for Spanish speakers. Mayo Test Drive’s web-based platform captures all item-level data to allow future item level analysis and application of machine learning techniques.

The broader aim of Mayo Test Drive is to provide infrastructure to include more tests, adaptations, and normative datasets to ultimately improve access and utility for diverse patient populations. Mayo Test Drive currently includes two measures: Stricker Learning Span (SLS), a novel learning and recognition memory test, and Symbols Test, an open access processing speed measure (Stricker et al., 2022; Wilks et al., 2022). The SLS was designed with consideration of learning principles from cognitive neuroscience to enhance detection of the early decline in learning observed in preclinical Alzheimer’s disease (AD). The SLS uses computer adaptive testing to adapt task difficulty trial-by-trial (e.g., increasing word span) and uses a sensitive 4-choice format to test recognition memory for each word. The SLS underwent initial piloting in older females to determine psychometric properties, test-retest reliability, convergent validity with traditional measures, and criterion validity (e.g., neuroanatomical associations).

Further validation and normative data development in the Mayo Clinic Study of Aging is ongoing, with additional criterion validation assessed by comparing brain PET (amyloid and tau) biomarker positive vs. negative groups. The SLS is equivalent to an inperson memory measure (AVLT), and the Mayo Test Drive composite including SLS and Symbols is superior to an in-person global screen (Short Test of Mental Status, like the MMSE) in distinguishing biomarker +/- older adults. To adapt the SLS for other languages/cultures, we have added community-based components to development (e.g., cognitive interviewing, additional piloting). We are beginning data-driven linguistic and remote cognitive interviewing approaches to develop an adaptation of the SLS for Spanish speakers. This study involves virtual focus groups with native Spanish speakers from different backgrounds (e.g., countries of origin, multilingualism) to examine the test paradigm, instructions, and items. Following piloting of the adaptations, next steps include normative data collection and clinical implementation. Future work involves in-person adaptation studies for lower/middle income countries including a collaboration with a Master’s level psychology graduate program in Grenada, West Indies to complete cognitive interviewing and pilot work with community members and stakeholders.

The dynamic transitions towards and away from digitizing mental health care services have put immense pressure on neuropsychology to develop a more technologically advanced approach to patient care. Consistent with this, neuropsychologists are faced with an increasing burden to rapidly learn novel techniques of administering digital and/or remote cognitive measures, which may not be sufficiently standardized and/or psychometrically validated.

The Hybrid Neuropsychology model, which aims to provide a framework for the integration of digital tools in neuropsychological assessment, has been incorporated routinely in our clinical practice, and among diverse clinical populations in inpatient and outpatient settings.

This talk aims to 1) provide a brief background on Hybrid Neuropsychology; 2) discuss preliminary findings from our ongoing studies implementing this approach in clinical populations; and 3) offer key insights gleaned from methodological, analytical, and practical perspectives.

Future work towards building a more integrative method of data collection and storage based on extant preliminary data will also be discussed.

The intricacies and difficulties in measuring forgetting rates, both in healthy participants and in clinical patients, have been intensively investigated since the 1970s. In recent years, there has been a revival of interest in ‘long-term’ forgetting rates, particularly in transient epileptic amnesia (TEA) and temporal lobe epilepsy (TLE), and some ‘old’ lessons have had to be re-learned.

Studies of long-term forgetting in patient groups will be reviewed, together with variables that influence different patterns of forgetting. In particular, I will report findings from two recent studies of TLE, as well as other related investigations.

Studies indicate that an impairment in memory ‘acquisition’, rather than differences in ‘long-term’ forgetting, appear critical in amnesic disorders, sometimes associated with differences in ‘early’ forgetting on recall memory measures only. An exception may be the effect of seizures, whether in consequence of epilepsy or ECT, which sometimes, but not always, appears to accelerate forgetting rates. Another important finding has been the pronounced variability in forgetting rates, both between individuals within a patient group and within individuals tested on separate occasions, making inferences from single-case studies problematical.

Findings will be interpreted in the light of these observations.

Health providers frequently probe patients’ recall of current and/or remote news items to determine the extent of memory loss. Impaired memory for transient events (i.e., in the news for a circumscribed time) may provide information regarding the onset of cognitive impairment. We utilized the Transient News Events Test (TNET) to explore how memory changes over time in older adults with cognitive impairment (CI) and non-cognitively impaired (NCI) individuals. We hypothesized that CI individuals would demonstrate reduced memory for transient events. We investigated the role of semantic and episodic memory on TNET performance.

Participants completed the TNET as part a comprehensive neuropsychological evaluation. Analyses included t tests to evaluate group differences for TNET performance, and correlations between TNET and neuropsychological measures, including episodic and semantic memory tests.

NCI adults demonstrated better memory than CI participants for TNET items. The NCI and CI groups did not differ regarding memory for remote items; however, CI participants had worse memory for recent items. There was a significant association between TNET performance and capacity for episodic and semantic memory in people with CI. In the NCI group, the TNET was associated only with episodic memory.

Findings support the use of news events to assess remote memories in older adults. Novel remote memory measures broaden the scope of memory assessment far beyond what is feasible within traditional neuropsychological assessment and provide insight into the onset of memory changes. Results enhance understanding of memory decline in older adults with cognitive impairment.

Accelerated long-term forgetting (ALF) has been reported in healthy older individuals, and is a possible early marker for risk of developing Alzheimer’s disease (AD). The Verbal Associative Learning & Memory Test (VALMT; McGibbon & Jansari, 2013) addresses methodological weaknesses in existing clinical tests and has detected ALF in epilepsy within an hour. We used VALMT to investigate learning and forgetting in healthy older participants.

Older (60-69yrs) and Younger (19-31yrs) participants were compared. Using VALMT, unrelated word-pairs were learned to criterion, then cued-recall was tested at delays of 5, 30 and 55 minutes. Unique pairs were tested at each delay. Subjective memory complaints data were gathered, and the Wechsler Memory Scale Logical Memory test (WMS-LM; a standard clinical measure) was administered.

VALMT identified a significant difference in delayed recall between Younger and Older groups by 55 minutes (d = 1.32). While 'fast-learning’ Older participants scored similarly to Younger participants, 'slow-learning’ Older participants were impaired at all delays. Forgetting rates suggested degradation of memory starts during early synaptic consolidation rather than later system-level consolidation. Increased subjective memory complaints were associated with reduced VALMT scores. By contrast, WMS-LM failed to identify significant differences between any groups, and did not correlate with memory complaints.

We conclude VALMT may be better able than WMS-LM to identify subtle impairments in healthy older adults within a single clinical visit, and VALMT results better reflect subjective experience. Older slow-learners forget faster and report more subjective memory complaints, which may indicate a group at risk of developing AD.

Long-term forgetting rates may be more sensitive for detecting memory decrements compared to short-delay memory assessments (e.g., after 20-30 minutes). To date, much research has been performed on accelerated long-term forgetting (ALF) in epilepsy patients, but research in other patient groups is lacking. ALF may be promising in the field of cerebrovascular disease, as many of these patients experience cognitive complaints, yet do not show impaired performances on neuropsychological assessments.

Here, I will present empirical findings on ALF in individuals after a TIA/minor stroke (n=30) and after stroke (n=91) using short- (20-30 min) and long-delay (1-week) memory testing.

After TIA/minor stroke, short-delay (2030 min) memory testing was unimpaired, but 1-week delayed testing showed an impaired performance compared to stroke-free controls. In the stroke group, ALF was present in 17% of the patients, compared to stroke-free controls, but more prevalent than rapid forgetting after short-delay memory testing.

ALF is present in patients with cerebrovascular disease, despite normal acquisition rates. The relation with neuroimaging findings and the clinical relevance of these results will be discussed.

To present the Mobile Toolbox (MTB), comprised of an expandable library of cognitive and other tests, including adapted versions of NIH Toolbox® measures. The MTB provides a complete research platform for app creation, study management, data collection, and data management. We will describe the MTB project and MTB research platform and demonstrate examples of assessments.

MTB is the product of an NIH-funded, multi-institutional effort involving Northwestern University, Sage Bionetworks, Penn State, University of California San Francisco, University of California San Diego, Emory University, and Washington University. The MTB assessment library is a dynamic repository built upon Sage Bionetworks mobile health platform. All MTB measures are created or adapted for a mobile interface using iOS and Android smartphones. Guided by the principles of open science, many components are open source to allow researchers and developers to integrate externally developed tests, including supplemental scales (e.g., passively collected contextual factors) assessing variables such as mood and fatigue that might influence cognitive test performance.

The current MTB library includes eight core cognitive tests based on well-established neuropsychological measures: two language tasks (Spelling and Word Meaning), two executive functioning tasks (Arrow Matching and Shape-Color Sorting), an associative memory task (Faces and Names), an episodic memory task (Arranging Pictures), a working memory task (Sequences) and a processing speed task (Numbers and Symbols). Additional cognitive assessments from other popular test libraries including the International Cognitive Ability Resource (ICAR), Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) and Test My Brain are currently being implemented, as are non-cognitive measures from the NIH Toolbox Emotion Battery and the Patient-Reported Outcomes Measurement Information System (PROMIS). The MTB library includes measures suitable for use in research studies incorporating point-in-time and burst designs as well as ecological momentary assessment (EMA).

The MTB was created to address many of the scientific, practical, and technical challenges to cognitive assessment by capitalizing on advances in technology measurement and cognitive research. Initial psychometric evaluation of measures has been performed, and additional clinical validation is underway in studies with persons at risk for cognitive impairment or Alzheimer’s disease (AD), diagnosed with mild cognitive impairment (MCI) or AD, Parkinson’s disease, and HIV-associated Neurocognitive Disorders. Calculation of norms and reliable change indicators is in progress. The MTB is currently available to beta testers with public release planned for Summer, 2023. Clinical researchers will be able to use the MTB system to design smartphone-based test batteries, deploy and manage mobile data collection in their research studies, and aggregate and analyze results in the context of large-scale norming data.

To present validation evidence for the first eight cognitive measures available through Mobile Toolbox (MTB). These measures use a remote self-administered platform to assess language, working memory, episodic memory, executive function, and processing speed.

We used two separate samples, recruited as part of a larger study, to validate MTB measures. Sample I, comprised of 92 English-speaking adults ages 18-85, was used to assess internal consistency and construct validity. Participants were first administered “gold standard” cognitive measures (Wechsler Memory Scale-IV Verbal Paired Associates I and II; Wechsler Adult Intelligence Scale-IV Symbol Search, Digit Span, Coding, and Letter-Number Sequencing; Delis-Kaplan Executive Function System Color-Word Interference Test, Peabody Picture Vocabulary Test, Wechsler Individual Achievement Test-4 Spelling, and the Wisconsin Card Sorting Test), after which they completed MTB (pre-loaded on a study-provided smartphone) on their own. Internal consistency was evaluated using measure-appropriate indices (split-half reliability, Cronbach’s alpha or IRT-based indices). Pearson correlation coefficients between MTB tests and measures of similar constructs were used to evaluate concurrent validity. For two tests with timing-dependent scores, Arrow Matching and Shape-Color Sorting, separate analyses were performed for iOS and Android devices. Sample II, with 1,120 English-speaking participants ages 18-90, was used to evaluate age-related change. Participants completed MTB measures remotely on their own smartphones, in a preset order, within a 14-day period. Spearman correlation coefficients, corrected for education, were calculated to evaluate relationships between age and test scores.

Sample I participants were 67% female, 52% white, 99% non-Hispanic; average age=48 (SD= 17). Education was: < high school (1%); high school (55%); some college (21%); college (15%); graduate degree (8%). Internal consistency estimates ranged from 0.81 to 0.99. Pearson correlations between MTB and external measures ranged from 0.41 to 0.86 (all p < .01). Of the timed tests, only Shape-Color sorting showed significant score differences between Android and iOS devices. Sample II was 57% female, 13% Hispanic, 72% white, mean age = 45 (SD = 21). Education distribution was: < high school (2%); high school (34%); some college (34%), college (20%); graduate degree (11%). Measures of executive function (r = -0.50; r=-0.57) and processing speed (r= -0.61) showed the expected negative correlation with age (all p <0.001). Negative correlations, although weaker, were also seen on measures of working memory (r=-0.2) and episodic memory (r=-0.2, r=-0.37; p.<.001). Vocabulary performance improved with age (r=0.4; p<.001), while spelling scores remained stable (r=0.09).

Initial studies support the validity and reliability of the first eight MTB cognitive measures in two diverse samples. MTB tests showed satisfactory construct validity, as demonstrated by the associations between MTB and well-established tests. Furthermore, most MTB measures correlated with age in the expected directions. Executive function, processing speed and memory typically decrease with age and this decrease was reflected in MTB test performance. In contrast, spelling and vocabulary, typically preserved as we age, did not decrease in our sample. Our results support the use of MTB in cognitive aging research.

A critical need in the neuropsychology field is development and validation of efficient, scalable assessments of cognition. The Mobile Toolbox (MTB), a novel suite of mobile device-compatible, app-based cognitive assessments, was developed to address this need. The goals of this study were (1) To collect longitudinal normative data for the MTB assessments in a large, ethnoculturally and educationally diverse cohort; (2) To assess the feasibility and usability of remote assessment using MTB.

Participants were recruited from the UCSF Brain Health Registry (BHR), an online cohort (N>100,000) that collects longitudinal cognitive, functional, behavioral, and health data using online neuropsychological tests and self- and study-partner report surveys. BHR participants who opted to learning about additional research opportunities were sent automated email invitations to enroll in the MTB study. Those who indicated study interest were provided instructions within the BHR online portal for downloading the MTB app. All participants had the opportunity to complete a single baseline administration of MTB (Word Meaning, Sequences, Spelling, Arranging Pictures, Arrow Matching, Faces and Names, Shape-Color Sorting, Number Match). Those who completed the baseline assessment within three days were invited to continue into the longitudinal study, where they complete MTB assessments at a single, short-term timepoint (day 7, 14, or 21; study arms sequentially assigned), and then at 6-month intervals. Enrollment across demographic groups was monitored, and study invitations were sent to specific demographic groups, with the goal of enrolling a sample of 800 participants in the longitudinal study: equal distribution across eight, 10-year age bands (ages 18-80+); 60% with <16 years of education; 10% non-Latinx Black, 15% Latinx, and 5% non-White other ethnocultural identity.

Between January-June 2022, 48,110 BHR participants were invited to the MTB study. Of those, 8294 (17%) expressed interest, 3401 (7%) completed the baseline assessment, 850 (1.8%) were assigned to the longitudinal study, and 782 (1.6%) completed a short-term longitudinal assessment. Study staff received 797 help tickets submitted by participants asking for email support to complete MTB. The baseline cohort had and average age of 64 years and an average of 16.6 years of education, 76.2% female, 2.1% non-Latinx Black, 7.1% Latinx, 86.8% non-Latinx White, and 4% from other ethnocultural groups. The longitudinal cohort had an average age of 62.3 years and an average of 16.1 years of education, 80% female, 2.8% non-Latinx Black, 8.5% Latinx, 83.5% non-Latinx White; and 5% other ethnocultural group. Compared to those invited to the study, those who enrolled in the longitudinal study were older, had higher educational attainment, and were more likely to be female and self-identify as non-Latinx White (p<0.05 for all).

Efficient enrollment and task completion of a large cohort in a novel, app-based mobile cognitive assessment is feasible in a completely remote setting. Most participants were able to complete MTB without individual support, indicating good usability. This approach can be scaled up to efficiently assess cognition in many research and healthcare settings. A remaining challenge is achieving robust ethnocultural and educational diversity.

To describe advantages and disadvantages of using digital assessments remotely and in-person to inform clinical and research practice.

As part of a larger study,1120 adults completed a battery of remotely administered tests (Mobile Toolbox) and a subset of this sample completed examiner administered in-person testing (NIH Toolbox® Cognition Battery). Attention was given to making the sample reflective of the US 2020 Census during participant recruitment. Of the 1120 participants, the majority of the sample were female (57%) and Caucasian (72%) and had a mean age of 45 (SD = 21). In terms of education, equal percentages had high school (34%) or some college (34%).

NIH Toolbox cognitive tests of processing speed, language, executive function, attention, and episodic memory were administered via a trained examiner and correlates of these tests were self-administered remotely via a smartphone. Using examples, we will show which aspects of cognitive assessment had the best correlations between remote self-administration and face-to-face examination and which had lower correlations.

Digital remote assessments can help overcome barriers by enabling repeated testing in naturalistic conditions, reducing participant burden and expense, and increasing research accessibility for populations currently under-represented. Moreover, the ubiquity of internet-connected devices vastly increases opportunities to remotely monitor other dimensions relevant to cognition using smartphone apps and wearable sensors. In addition to improving access to testing, digitally administered assessments dramatically improve some individual’s tolerance to testing with shorter tests that can be administered via computer adaptive testing (CAT). Despite these benefits, some aspects of the cognitive assessment cannot be adequately replicated remotely and thus yield lower correlations to their examiner-administered alternatives. Clinical and research implications are discussed.

Social determinants of health (SDoH) are structural elements of our living and working environments that fundamentally shape health risks and outcomes. The Healthy People 2030 campaign delineated SDoH into five distinct categories that include: economic stability, education access/quality, healthcare access, neighborhood and built environment, and social and community contexts. Recent research has demonstrated that minoritized individuals have greater disadvantage across SDoH domains, which has been linked to poorer cognitive performance in older adulthood. However, the independent effects of SDoH on everyday functioning across and within racial groups remains less clear. The current project explored the association between SDoH factors and 10-year change in everyday functioning in a large sample of community-dwelling Black and White older adults.

Data from 2,505 participants without dementia enrolled in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (age M=73.5; 76% women; 28% Black/African American). Sociodemographic, census, and industry classification data were reduced into five SDoH factors: economic stability, education access and quality, healthcare access and quality, neighborhood and built environment, and social and community contexts. The Observed Tasks of Daily Living, a performance-based measure of everyday functioning with tasks involving medication management, finances, and telephone use, was administered at baseline, 1-, 2-, 3-, 5, and 10-year follow up visits. Mixed-effects models with age as the timescale tested (1) racial group differences in OTDL trajectories, (2) race x SDOH interactions on OTDL trajectories, and (3) associations between SDoH and OTDL trajectories stratified within Black and White older adults. Covariates included sex/gender, vocabulary score, Mini-Mental Status Examination, depressive symptoms, visual acuity, general health, training group status, booster status, testing site, and recruitment wave.

Black older adults had a steeper decline of OTDL performance compared to Whites (linear: b = -.25, quadratic b=-.009, ps < .001). There was a significant race x social and community context interaction on linear OTDL trajectories (b =.06, p=.01), but no other significant race x SDoH interactions were observed (bs =-.007-.05, ps=.73-.11). Stratified analyses revealed lower levels of social and community context were associated with steeper age-related linear declines in OTDL performance in Black (b = .08, p=.001), but not White older adults (b =.004, p=.64). Additionally, lower levels of economic stability were associated with steeper age-related linear declines in OTDL performance in Black (b =.07, p=.04), but not White older adults (b =.01, p=.35). Finally, no significant associations between other SDoH and OTDL trajectories were observed in Black (bs = -.04-.01, ps =.09-.80) or White (bs = -.02-.003, ps=.07-.96) older adults.

SDoH, which measure aspects of structural racism, play an important role in accelerating age-related declines in everyday functioning. Lower levels of economic and community-level social resources are two distinct SDoH domains associated with declines in daily functioning that negatively impact Black, but not White, older adults. It is imperative that future efforts focus on both identifying and acting upon upstream drivers of SDoH-related inequities. Within the United States, this will require addressing more than a century of antiBlack sentiment, White supremacy, and unjust systems of power and policies designed to intentionally disadvantage minoritized groups.

Prior work with older adults has shown that participating in a range of physical, social, and cognitive activities provides great benefits, such as improved mood and cognitive functioning. These activities can protect against common cognitive problems associated with aging (e.g., poor working memory and processing speed) and lower the risk of developing dementia, thus supporting the cognitive reserve hypothesis. Cognitive reserve refers to the preservation of an individual’s cognitive abilities over time despite changes in the brain that allows them to be resilient in performing daily and complex tasks (Stern, 2012). Historical factors such as education, life experiences, and occupational complexity, as well as current lifestyle behaviors such as cognitive and social activities may serve as proxies for cognitive reserve. It is not clear whether historical proxies of cognitive reserve (e.g., educational attainment) interact with more proximal lifestyle factors (e.g., recent cognitive stimulation) to impact cognitive functioning. In this study, we examined if education, recent cognitive activity, and their interaction predicted enhanced immediate memory and visual and verbal working memory in middle-aged to older adults.

Participants were 62 middle-aged to older adults (age 45-93; mean age = 65.9 years; 80.6% female; 70.9% Black; ∼75.0% with high school education or higher) recruited from a Louisiana housing facility for seniors with low or fixed incomes and a local community center. Data collection included the CHAMPS Physical Activity Questionnaire for Older Adults, Wechsler Adult Intelligence Scale subtests (Digit Span Forward and Digit Span Backward), and the Size Judgment Span Task. Mixed-effects regression analyses were performed with education (less than high school, high school, college), the CHAMPS cognitive activity composite (Weaver & Jaeggi, 2021), and an education * cognitive activity interaction term as independent variables and cognitive test scores as the outcome variables. All models controlled for age and race/ethnicity.

Significant education by cognitive activity effects were observed for Digit Span Backward and Size Judgment Span, but not for Digit Span Forward. The interactions reflected a positive association between cognitive activity and cognitive functioning in people with at least a high school education, but not in people with less than a high school education.

Our results support previous findings that education level and engagement in cognitive activity may serve as protective factors against cognitive decline in later life. The finding that cognitive activity was not associated with better cognitive functioning at lower levels of education suggest that earlier life experiences may moderate the benefit of lifestyle interventions later in life. Future studies should examine whether other lifestyle interventions, such as exercise, are more beneficial for people with less cognitive reserve from earlier life experiences.

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.

Higher levels of inflammation are associated with risk factors for Alzheimer’s disease and related dementias (ADRD) in older Black adults including psychosocial stressors (e.g., discrimination and early life adversity) and white matter alterations. Yet, limited work has investigated these risk factors together in a longitudinal neuroimaging study, despite the well-known ADRD disparity in older Black adults. Using data from the Minority Aging Research Study and African American Clinical Core of the Rush Alzheimer’s Disease Center, we examined interactions of psychosocial stressors and change in inflammation on changes in white matter integrity as measured via diffusion tensor imaging (DTI).

Older Black adults (n=102) without known dementia at baseline (age=75.8±6.1 years; 87.3% female; education=15.4±2.7 years) completed blood draws at two time points (follow-up=2.4±0.7 years), neuroimaging at two or more time points (follow-up=3.7±1.8 years), and psychosocial questionnaires at one time point coinciding with the first blood draw/neuroimaging. Blood serum was assayed using highly-sensitive multiplexed sandwich ELISA for interleukin-6, c-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-a) and a change score was calculated for each inflammatory marker (T2 - T1). The Williams Everyday Discrimination Scale quantified experiences of discrimination in all participants and a 16-item questionnaire of emotional and physical trauma from age 0-18 assessed early life adversity in a participant subset (n=63). DTI-derived tract-based spatial statistics (TBSS) slope change measures for trace of the diffusion tensor, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were calculated, with the first two scans matched in time to blood assays. Linear regression models investigated interactions of each inflammatory marker change score (separately) and either discrimination or early life adversity (separately) on trace, FA, AD, and RD slopes as individual outcomes adjusting for age, sex, education, white matter hyperintensities (total volume and voxelwise), cardiovascular risk factors, statin and analgesic medications, thyroid conditions, and depression. Statistical significance was determined at p<0.05 using family wise error correction and threshold free cluster enhancement.

Discrimination moderated the relationship between TNF-a and AD whereby those with increasing TNF-a and higher levels of discrimination had increasing levels of AD over time in white matter tracts connecting the left and right cerebellum, the left pallidum and medulla, and the left superior frontal gyrus and left thalamus. Both discrimination and early life adversity moderated associations between CRP and AD, where increases in CRP and higher psychosocial stressors (of either type) resulted in decreasing AD over time in tracts involving cingulate, frontal, and parietal regions. Discrimination and early life adversity also moderated associations between CRP and RD, where increasing CRP combined with greater psychosocial stressors resulted in decreasing RD in right hemisphere association and projection tracts connecting frontal, parietal, central, and subcortical regions.

TNF-a and CRP interacted with measures of psychosocial stress to associate with DTI-derived TBSS slope change measures of AD and RD in differential, and at times, paradoxical ways. Findings suggest that both risk and resilience as related to brain connectivity may be co-occurring in the presence of psychosocial stressors for older Black adults.