Debra A. Fleischman

INTRODUCTION: Older Black adults are at risk of cerebral small vessel disease (CSVD), which contributes to dementia risk. Two subtypes of CSVD, arteriolosclerosis and ischemic lacunar infarcts, have been independently linked to lower cognition and higher dementia risk, but their combined effects on cognition in older Black adults are unclear.METHODS: Mixed models were used to examine the associations of in vivo measures of arteriolosclerosis (ARTS) and ischemic lacunar infarcts to cognitive level and change in 370 older Black adults without dementia. RESULTS: Modeled together, higher ARTS load accounted for lower levels of global cognition, episodic memory, semantic memory, and perceptual speed, whereas higher infarct load accounted for lower levels of working memory. There were no associations with rate of cognitive change.DISCUSSION: Both arteriolosclerosis and ischemic infarcts impact the cognitive health of older Black adults, but arteriolosclerosis affects cognition more broadly and offers promise as an in vivo biomarker of dementia risk.Highlights: Older Black adults are at risk of cerebral small vessel disease (CSVD) and dementia. Examined magnetic resonance imaging‐derived measure of arteriolosclerosis (ARTS), infarcts, and cognition. ARTS load was widely associated with lower cognition after adjusting for infarct load. Infarct load was specifically associated with lower complex attention. More within‐Black in vivo studies of CSVD subtypes and cognition are needed.

Background: Latinos are at higher risk of developing mild cognitive impairment (MCI) and Alzheimer’s disease than non-Latino Whites. Acculturation factors may influence this risk, yet there are few studies that have examined associations of acculturation, particularly in the context of socioenvironmental and familial factors, and brain health in older Latinos. Objective: To examine potential associations between acculturation in context and brain health in older Latinos. Methods: Using three previously established composites of acculturation-in-context, (acculturation-related: nativity status, language preference, acculturation scores; contextually-related socioenvironmental: perceived discrimination, loneliness/social isolation, social network size; and familism), and diffusion-tensor imaging (DTI), associations with white matter structural integrity were examined in 92 Latino adults without dementia participating in one of three epidemiological studies of aging. Linear regression models were used to test associations with DTI-derived metrics (fractional anisotropy, FA; trace) as separate outcomes and acculturation composite scores as individual predictors, while adjusting for age, sex, education, scanner, and white matter hyperintensities (voxelwise and total volumes normalized by intracranial volume). Results: Higher scores on the socioenvironmental composite were associated with lower FA in two clusters of left-hemisphere connections. Cluster 1 was dominated by both short association pathways connecting frontal regions and projection pathways connecting frontal regions with the thalamus. Cluster 2 was dominated by long association pathways connecting parietal, frontal, and temporal regions. Conclusions: This study of older Latino adults demonstrated an association between reduced brain white matter integrity and contextually related socioenvironmental experiences known to increase risk of MCI and Alzheimer’s disease.

Background: The COVID pandemic has brought death and dying to the forefront, contributing to the already high levels of physician burnout. Furthermore, there is a negative correlation between physician burnout and empathy. Due to time constraints of clinical rotations in traditional medical education, there are often shortcomings in students’ understanding of how to best manage and communicate with chronically or terminally ill patients. This study implements a distributive model of a virtual reality (VR)‐based curriculum, utilizing vignettes that portray a Latinx woman, Beatriz, with Alzheimer’s disease, and a veteran, Clay, with cancer transitioning to hospice from a first‐person perspective.Method: Medical and premedical students in Chicago were recruited (N = 12, 75% female, 58% White, 58% M2) and engaged in a self‐directed VR‐based curriculum, including Embodied Labs modules and corresponding lectures from expert physicians. Lecture content time was 2 hours 40 minutes and VR module time was 35 minutes, which students completed at their own pace prior to a Zoom group discussion. Participants completed a series of pre‐ and post‐surveys.Result: Preliminary qualitative analysis reveals participant‐perceived increased competencies in the following themes: medical knowledge and preparedness (100%), compassion and empathy (67%), communication and patience (50%), emotional connection and advocacy (50%), and family values and comfort (42%) after program completion. Moreover, 11/12 participant reflections either directly stated the value of this experience for their professional development or explicitly highlighted its utility within medical school curricula. Additional qualitative content analyses and quantitative statistics on the changes in pre‐ and post‐survey measures are forthcoming.Conclusion: Burnout and reduced patient‐centered‐care have been identified as barriers to empathic delivery of care in the COVID era. Utilizing VR to develop a medical curriculum fosters increased compassion and empathy in the context of dementia and end‐of‐life care. This multi‐dimensional curriculum can be scaled and implemented virtually to mitigate the impact of burnout on empathy in trainees caring for patients during the pandemic. Future aims include formally integrating this model into a medical curriculum, targeting students early in their career before they are overwhelmed with burnout, and broadening content to include trainees from diverse medical professional programs and institutions.

Introduction: Older Black adults experience a high burden of depressive symptoms and cerebrovascular disease but the specific neurobiological substrates underlying the association between late-life depressive symptoms and brain integrity are understudied, particularly in within-group designs.Methods: Using the Center for Epidemiologic Studies Depression Scale and diffusion-tensor imaging, within-Black variation in the association between late-life depressive symptoms and white matter structural integrity was examined in 297 older Black participants without dementia that were enrolled across three epidemiological studies of aging and dementia. Linear regression models were used to test associations with DTI metrics (fractional anisotropy, trace of the diffusion tensor) as the outcomes and depressive symptoms as the predictor, while adjusting for age, sex, education, scanner, serotonin-reuptake inhibitor use, total volume of white-matter hyperintensities normalized by intracranial volume, and presence of white-matter hyperintensities at the voxel level.Results: Higher level of self-reported late-life depressive symptoms was associated with greater diffusion-tensor trace (reduced white matter integrity) in connections between commissural pathways and contralateral prefrontal regions (superior and middle frontal/dorsolateral prefrontal cortex), association pathways connecting dorsolateral prefrontal cortex with insular, striatal and thalamic regions, and association pathways connecting the parietal, temporal and occipital lobes and the thalamus.Discussion: This study demonstrated a discernable pattern of compromised white matter structural integrity underlying late-life depressive symptoms within older Black adults.

Background: We previously outlined the importance of considering acculturation within the context of older Latino adults' lived experience (ie, acculturation in context) to better capture contributors to cognitive aging. We now examine this conceptual framework as related to level of and change in cardiovascular health, and whether cardiovascular health modifies previously documented associations of acculturation in context with cognition. Methods and Results: Acculturation in context data from 192 Latino participants without dementia at baseline (age ~70 years) were compiled into 3 separate composite scores: acculturation‐related (nativity, language‐, and social‐based preferences), contextually related socioenvironmental (experiences of discrimination, social isolation, social networks), and familism‐related (Latino‐centric family ethos). A modified American Heart Association's Life's Simple 7 (mLS7; ie, smoking, physical activity, body mass index, blood pressure, total cholesterol, blood glucose) was used to measure cardiovascular health. Mixed effects regressions simultaneously tested the association of all 3 composite scores with total mLS7 adjusting for confounders. Separate models tested whether mLS7 modified associations of the 3 composite scores and cognition. The contextually related socioenvironmental composite score reflecting higher discrimination, higher social isolation, and smaller social networks (estimate=0.22, SE=0.10, P =0.02) and the familism score (estimate=0.16, SE=0.07, P =0.02) both significantly associated with change in total mLS7. The acculturation‐related composite was not significantly associated with change in mLS7. No composite was significantly associated with level of mLS7. Total mLS7, however, significantly modified associations between the acculturation‐related composite and change in working memory (estimate=−0.02, SE=0.01, P =0.043). Conclusions: Acculturation within the context of older Latino adults' lived experience is important for maintaining cardiovascular health, relationships that also affect domain‐specific cognitive decline.

Objective HIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults. Methods Cross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1β, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined. Results No inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition. Conclusion Immune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.

BACKGROUND AND PURPOSE: The entorhinal cortex, a critical gateway between the neocortex and hippocampus, is one of the earliest regions affected by Alzheimer disease–associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging–based measure of the entorhinal cortex, whether antemortem entorhinal cortex thickness is associated with postmortem tangle burden within the entorhinal cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of entorhinal cortex thickness and postmortem neuropathological measures. MATERIALS AND METHODS: We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the entorhinal cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between entorhinal cortex thickness and tangles and amyloid-β load within the entorhinal cortex and medial temporal and neocortical regions. RESULTS: We found a significant relationship between antemortem entorhinal cortex thickness and entorhinal cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between entorhinal cortex thickness and entorhinal cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between entorhinal cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and entorhinal cortex (P = .31) and medial temporal lobe tangles (P = .051). CONCLUSIONS: Our findings indicate that entorhinal cortex–associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.