What does Juneteenth mean in STEMM?

Juneteenth commemorates the freeing of the last large group of enslaved people in 1865 at the end of the American Civil War. We asked several Black scientists what Juneteenth means to them in the context of science, technology, engineering, mathematics, and medicine (STEMM)? Their answers run the emotional gamut.

Empirically derived psychosocial-behavioral phenotypes in Black/African American and Hispanic/Latino older adults enrolled in HABS-HD: Associations with AD biomarkers and cognitive outcomes.

INTRODUCTION: Identification of psychosocial-behavioral phenotypes to understand within-group heterogeneity in risk and resiliency to Alzheimer's disease (AD) within Black/African American and Hispanic/Latino older adults is essential for the implementation of precision health approaches. METHODS: A cluster analysis was performed on baseline measures of socioeconomic resources (annual income, social support, occupational complexity) and psychiatric distress (chronic stress, depression, anxiety) for 1220 racially/ethnically minoritized adults enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD). Analyses of covariance adjusting for sociodemographic factors examined phenotype differences in cognition and plasma AD biomarkers. RESULTS: The cluster analysis identified (1) Low Resource/High Distress (n = 256); (2) High Resource/Low Distress (n = 485); and (3) Low Resource/Low Distress (n = 479) phenotypes. The Low Resource/High Distress phenotype displayed poorer cognition and higher plasma neurofilament light chain; differences between the High Resource/Low Distress and Low Resource/Low Distress phenotypes were minimal. DISCUSSION: The identification of psychosocial-behavioral phenotypes within racially/ethnically minoritized older adults is crucial to the development of targeted AD prevention and intervention efforts.

Lower Body Mass Index at Baseline Is Related to Steeper Cognitive Decline in the Alzheimer's Disease Neuroimaging Initiative Cohort.

OBJECTIVE: Midlife obesity is a risk factor for dementia, whereas obesity in older age may be protective of cognition, a phenomenon known as the "obesity paradox." The mechanisms underlying this phenomenon and the relationship between body mass index (BMI) and cognitive function over time remain unclear. METHODS: In 1399 adults with and without mild cognitive impairment (median age 73.6 years) from the Alzheimer's Disease Neuroimaging Initiative, we modeled the effects of baseline BMI on within-person trajectories of cognitive decline using Latent Growth Curve Modeling. We also tested if the effects of BMI on cognitive decline are global or specific to memory, executive function, or language. RESULTS: Higher baseline BMI was associated with better memory ( ßBMI = 0.06, p < .05) and worse executive function ( ßBMI = -0.05, p < .05) and not associated with language. Independent of baseline diagnosis, higher baseline BMI was associated with slower rate of decline in executive function, memory, and language ( ßBMI = 0.13, 0.12, and 0.12, respectively; p < .01). Higher BMI was not associated with the intercept ( ßBMI = 0.04, p = .059) or change ( ßBMI = 0.04, p = .415) in a global cognitive factor. CONCLUSIONS: We found that higher baseline BMI was associated with slower cognitive decline in participants with and without mild cognitive impairment diagnosis. Higher BMI in this context seems to be protective of cognitive function for people at risk for dementia. Our findings also support domain-specific effects of obesity on various cognitive functions rather than a final common pathway.

Research Letter: TBI Severity Moderates the Association Between Subjective and Objective Attention in Older Veterans.

OBJECTIVE: This study examined the moderating effect of traumatic brain injury (TBI) history on subjective and objective cognition across multiple cognitive domains. SETTING, PARTICIPANTS, AND DESIGN: Participants included 242 Vietnam-era veterans with a history of no TBI (n = 86), mild TBI (n = 74), or moderate-to-severe TBI (n = 82) from the observational Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DoD-ADNI) study. MAIN MEASURES: Objective cognition was the outcome and was measured using neuropsychological measures in the domains of memory, attention/executive functioning, and language. Subjective cognition was measured using the memory, divided attention, and language subscales from the Everyday Cognition (ECog) measure. TBI severity status was the moderating variable. RESULTS: Veterans with a history of moderate-to-severe TBI had a stronger negative association between subjective and objective attention relative to participants without a TBI (P = .002). Although this association did not differ between mild TBI and no TBI history groups (P = .100), the association between subjective and objective attention for the mild TBI group was intermediate to the no TBI and moderate-to-severe TBI history groups. TBI status did not moderate associations between subjective and objective memory or language. CONCLUSION: Results highlight the importance of assessing subjective and objective cognition in older veterans and the relevance of attention in the context of TBI history. More work is needed to better understand the intersection of TBI and aging and how these factors may be used to guide individualized assessment and treatment approaches for older veterans.

Diffusion MRI tractography of the locus coeruleus-transentorhinal cortex connections using GO-ESP.

PURPOSE: The locus coeruleus (LC) is implicated as an early site of protein pathogenesis in Alzheimer's disease (AD). Tau pathology is hypothesized to propagate in a prion-like manner along the LC-transentorhinal cortex (TEC) white matter (WM) pathway, leading to atrophy of the entorhinal cortex and adjacent cortical regions in a progressive and stereotypical manner. However, WM damage along the LC-TEC pathway may be an earlier observable change that can improve detection of preclinical AD. THEORY AND METHODS: Diffusion-weighted MRI (dMRI) allows reconstruction of WM pathways in vivo, offering promising potential to examine this pathway and enhance our understanding of neural mechanisms underlying the preclinical phase of AD. However, standard dMRI analysis tools have generally been unable to reliably reconstruct this pathway. We apply a novel method, geometric-optics based entropy spectrum pathways (GO-ESP) and produce a new measure of connectivity: the equilibrium probability (EP). RESULTS: We demonstrated reliable reconstruction of LC-TEC pathways in 50 cognitively normal older adults and showed a negative association between LC-TEC EP and cerebrospinal fluid tau. Using Human Connectome Project data, we demonstrated replicability of the method across acquisition schemes and scanners. Finally, we compared our findings with the only other existing LC-TEC tractography template, and replicated their pathway as well as investigated the source of these discrepant findings. CONCLUSIONS: AD-related tau pathology may be detectable within GO-ESP-identified LC-TEC pathways. Furthermore, there may be multiple possible routes from LC to TEC, raising important questions for future research on the LC-TEC connectome and its role in AD pathogenesis.

Laterality of motor symptom onset and facial expressivity in Parkinson disease using face digitization.

The onset of motor symptoms in Parkinson disease (PD) is typically unilateral. Previous work has suggested that laterality of motor symptoms may also influence non-motor symptoms including cognition and emotion perception. In line with hemispheric differences in emotion processing, we tested whether left side/right brain motor onset was associated with worse expression of facial affect when compared to right side/left brain motor onset. We evaluated movement changes associated with facial affect in 30 patients with idiopathic PD (15 left-sided motor onset, 15 right-sided motor onset) and 20 healthy controls. Participants were videotaped while posing three facial expressions: fear, anger, and happiness. Expressions were digitized and analyzed using software that extracted three variables: two measures of dynamic movement change (total entropy and entropy percent change) and a measure of time to initiate facial expression (latency). The groups did not differ in overall amount of movement change or percentchange. However, left-sided onset PD patients were significantly slower in initiating anger and happiness facial expressions than were right-sided onset PD patients and controls. Our results indicated PD patients with left-sided symptom onset had greater latency in initiating two of three facial expressions, which may reflect laterality effects in intentional behaviour.

Elevated Intraindividual Variability in Executive Functions and Associations with White Matter Microstructure in Veterans with Mild Traumatic Brain Injury.

OBJECTIVE: We examined whether intraindividual variability (IIV) across tests of executive functions (EF-IIV) is elevated in Veterans with a history of mild traumatic brain injury (mTBI) relative to military controls (MCs) without a history of mTBI. We also explored relationships among EF-IIV, white matter microstructure, and posttraumatic stress disorder (PTSD) symptoms. METHOD: A total of 77 Veterans (mTBI = 43, MCs = 34) completed neuropsychological testing, diffusion tensor imaging (DTI), and PTSD symptom ratings. EF-IIV was calculated as the standard deviation across six tests of EF, along with an EF-Mean composite. DSI Studio connectometry analysis identified white matter tracts significantly associated with EF-IIV according to generalized fractional anisotropy (GFA). RESULTS: After adjusting for EF-Mean and PTSD symptoms, the mTBI group showed significantly higher EF-IIV than MCs. Groups did not differ on EF-Mean after adjusting for PTSD symptoms. Across groups, PTSD symptoms significantly negatively correlated with EF-Mean, but not with EF-IIV. EF-IIV significantly negatively correlated with GFA in multiple white matter pathways connecting frontal and more posterior regions. CONCLUSIONS: Veterans with mTBI demonstrated significantly greater IIV across EF tests compared to MCs, even after adjusting for mean group differences on those measures as well as PTSD severity. Findings suggest that, in contrast to analyses that explore effects of mean performance across tests, discrepancy analyses may capture unique variance in neuropsychological performance and more sensitively capture cognitive disruption in Veterans with mTBI histories. Importantly, findings show that EF-IIV is negatively associated with the microstructure of white matter pathways interconnecting cortical regions that mediate executive function and attentional processes.

Research Letter: PTSD Symptom Severity and Multiple Traumatic Brain Injuries Are Associated With Elevated Memory Complaints in Veterans With Histories of Mild TBI.

OBJECTIVE: The evaluation of memory complaints in mild traumatic brain injury (mTBI) remains an important clinical consideration, especially in the context of comorbid psychiatric symptoms such as posttraumatic stress disorder (PTSD). We compared subjective memory complaints in veterans with and without a history of mTBI, examined ratings between those with single versus multiple mTBIs, and investigated associations between memory complaints and PTSD symptom severity. METHODS: 117 outpatient veterans (mTBI: n = 79 [single mTBI: n = 22, multiple mTBI: n = 57], military controls [MCs]: n = 38) completed a TBI history assessment, the Prospective-Retrospective Memory Questionnaire (PRMQ), and the PTSD Checklist-Military Version (PCL-M). RESULTS: Hierarchical multiple regression showed that greater PCL-M scores significantly predicted elevated PRMQ-Total scores, accounting for 38% of the variance explained (P < .001). mTBI status predicted an additional 5% of variance in memory complaints (P < .01). The multiple-mTBI group endorsed more memory complaints than either MCs (P < .01) or the single-mTBI group (P < .05), who did not differ from MCs (P > .50). CONCLUSIONS: Comorbid PTSD symptoms are an important factor when considering memory complaints in veterans with a reported history of mTBI. However, independent of comorbid PTSD symptoms, mTBI status-particularly in the context of repetitive neurotrauma-uniquely contributes to memory complaints. Findings suggest that veterans with a history of multiple mTBIs may be a particularly vulnerable group in need of specialized interventions and/or psychoeducation.

Elevated plasma neurofilament light predicts a faster rate of cognitive decline over 5 years in participants with objectively-defined subtle cognitive decline and MCI.

INTRODUCTION: Neurofilament light (NFL) reflects neuroaxonal damage and is implicated in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known about NFL in pre-MCI stages, such as in individuals with objectively-defined subtle cognitive decline (Obj-SCD). METHODS: Two hundred ninety-four participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent baseline blood draw and serial neuropsychological testing over 5 years of follow-up. RESULTS: Individuals with Obj-SCD and MCI showed elevated baseline plasma NFL relative to the cognitively normal (CN) group. Across the sample, elevated NFL predicted faster rate of cognitive and functional decline. Within the Obj-SCD and MCI groups, higher NFL levels predicted faster rate of decline in memory and preclinical AD composite score compared to the CN group. DISCUSSION: Findings demonstrate the utility of plasma NFL as a biomarker of early AD-related changes, and provide support for the use of Obj-SCD criteria in clinical research to better capture subtle cognitive changes.

Fatigue Is Associated With Global and Regional Thalamic Morphometry in Veterans With a History of Mild Traumatic Brain Injury.

OBJECTIVE: Fatigue is a complex, multidimensional phenomenon that commonly occurs following traumatic brain injury (TBI). The thalamus-a structure vulnerable to both primary and secondary injuries in TBI-is thought to play a pivotal role in the manifestation of fatigue. We explored how neuroimaging markers of local and global thalamic morphometry relate to the subjective experience of fatigue post-TBI. METHODS: Sixty-three Veterans with a history of mild TBI underwent structural magnetic resonance imaging and completed questionnaires related to fatigue and psychiatric symptoms. FMRIB's Software (FSL) was utilized to obtain whole brain and thalamic volume estimates, as well as to perform regional thalamic morphometry analyses. RESULTS: Independent of age, sex, intracranial volume, posttraumatic stress disorder, and depressive symptoms, greater levels of self-reported fatigue were significantly associated with decreased right (P = .026) and left (P = .046) thalamic volumes. Regional morphometry analyses revealed that fatigue was significantly associated with reductions in the anterior and dorsomedial aspects of the right thalamic body (P < .05). Similar trends were observed for the left thalamic body (P < .10). CONCLUSIONS: Both global and regional thalamic morphometric changes are associated with the subjective experience of fatigue in Veterans with a history of mild TBI. These findings support a theory in which disruption of thalamocorticostriatal circuitry may result in the manifestation of fatigue in individuals with a history of neurotrauma.

Predictors of cognitive and physical fatigue in post-acute mild-moderate traumatic brain injury.

Post-traumatic fatigue (PTF) is a common, disabling, and often chronic symptom following traumatic brain injury (TBI). Yet, the impact of chronic cognitive and physical fatigue and their associations with psychiatric, sleep, cognitive, and psychosocial sequelae in mild-moderate TBI remain poorly understood. Sixty Veterans with a history of mild-moderate TBI and 40 Veteran controls (VC) were administered the Modified Fatigue Impact Scale, a validated measure of TBI-related cognitive and physical fatigue as well as measures of neuropsychiatric, psychosocial, sleep, and objective cognitive functioning. Compared to VC, TBI Veterans endorsed significantly greater levels of cognitive and physical fatigue. In TBI, psychiatric symptoms, sleep disturbance, and post-traumatic amnesia (PTA) were associated with both cognitive and physical fatigue, while loss of consciousness (LOC) and poor attention/processing speed were related to elevations in cognitive fatigue only. In regression analyses, anxiety, sleep disturbance, and LOC significantly predicted cognitive fatigue, while only post-traumatic stress symptoms and PTA contributed to physical fatigue. Cognitive and physical fatigue are problematic symptoms following mild-moderate TBI that are differentially associated with specific injury and psychiatric sequelae. Findings provide potential symptom targets for interventions aimed at ameliorating fatigue, and further underscore the importance of assessing and treating fatigue as a multi-dimensional symptom following TBI.

Neuropsychiatric Predictors of Post-Injury Headache After Mild-Moderate Traumatic Brain Injury in Veterans.

OBJECTIVES: To determine differences in neuropsychiatric complaints between Veterans with mild to moderate traumatic brain injury (TBI), with and without headache, compared with Veteran controls, and to identify neuropsychiatric predictors of headache severity. BACKGROUND: Mild to moderate TBI is a common occurrence in Veterans, and is frequently associated with complaints of headache. Neuropsychiatric complaints are also common among individuals who have sustained head injury, although the relationship between these factors and headache after injury is unclear. Research is needed to comprehensively determine differences between individuals with mild to moderate traumatic brain injury who differ with respect to headache, and which injury, psychological, or sleep and fatigue factors predict headache severity. METHODS: A cross-sectional study compared 85 Veterans in three groups (positive for TBI and headache, positive for TBI without significant headache, and a control group) on a set of injury characteristics and neuropsychiatric variables. Correlates of headache severity were examined, and a regression model was used to identify significant independent predictors of headache severity. RESULTS: Individuals with mild to moderate TBI and headache endorsed significantly greater neuropsychiatric symptoms than participants in the other groups (η(p)2 = .23-.36) Neuropsychiatric complaints, as well as presence of posttraumatic amnesia, were correlated with headache in the subsample with TBI (rs = .44-.57). When entering all predictors into a regression model, only fatigue represented a significant independent predictor of headache severity (ß = .59, R2 = .35). CONCLUSIONS: Rather than being a global risk factor, mild to moderate TBI was associated with poorer mental health outcomes, particularly for those who endorse headache. Findings underscore the possibility that Veterans with history of TBI who present with complaints of headache may represent a particularly vulnerable subgroup. Additionally, our findings suggest that clinical outcomes may be improved in those with neurotrauma by incorporating a focus on fatigue in treatment.

White Matter Associations With Performance Validity Testing in Veterans With Mild Traumatic Brain Injury: The Utility of Biomarkers in Complicated Assessment.

OBJECTIVE: Failure on performance validity tests (PVTs) is common in Veterans with histories of mild traumatic brain injury (mTBI), leading to questionable validity of clinical presentations. PARTICIPANTS: Using diffusion tensor imaging, we investigated white matter (WM) integrity and cognition in 79 Veterans with history of mTBI who passed PVTs (n = 43; traumatic brain injury [TBI]-passed), history of mTBI who failed at least 1 PVT (n = 13; TBI-failed), and military controls (n = 23; MCs) with no history of TBI. RESULTS: The TBI-failed group demonstrated significantly lower cognitive scores relative to MCs and the TBI-passed group; however, no such differences were observed between MCs and the TBI-passed group. On a global measure of WM integrity (ie, WM burden), the TBI-failed group showed more overall WM abnormalities than the other groups. However, no differences were observed between the MCs and TBI-passed group on WM burden. Interestingly, regional WM analyses revealed abnormalities in the anterior internal capsule and cingulum of both TBI subgroups relative to MCs. Moreover, compared with the TBI-passed group, the TBI-failed group demonstrated significantly decreased WM integrity in the corpus callosum. CONCLUSIONS: Findings revealed that, within our sample, WM abnormalities are evident in those who fail PVTs. This study adds to the burgeoning PVT literature by suggesting that poor PVT performance does not negate the possibility of underlying WM abnormalities in military personnel with history of mTBI.

White Matter Microstructural Compromise Is Associated With Cognition But Not Posttraumatic Stress Disorder Symptoms in Military Veterans With Traumatic Brain Injury.

OBJECTIVE: To investigate white matter microstructure compromise in Veterans with a history of traumatic brain injury (TBI) and its possible contribution to posttraumatic stress disorder (PTSD) symptomatology and neuropsychological functioning via diffusion tensor imaging. PARTICIPANTS AND METHODS: Thirty-eight Veterans with mild (n = 33) and moderate (n = 5) TBI and 17 military control participants without TBI completed neuropsychological testing and psychiatric screening and underwent magnetic resonance imaging an average of 4 years following their TBI event(s). Fractional anisotropy (FA) and diffusivity measures were extracted from 9 white matter tracts. RESULTS: Compared with military control participants, TBI participants reported higher levels of PTSD symptoms and performed worse on measures of memory and psychomotor-processing speed. Traumatic brain injury was associated with lower FA in the genu of the corpus callosum and left cingulum bundle. Fractional anisotropy negatively correlated with processing speed and/or executive functions in 7 of the 8 tracts. Regional FA did not correlate with memory or PTSD symptom ratings. CONCLUSION: Results suggest that current PTSD symptoms are independent of TBI-related white matter alterations, as measured by diffusion tensor imaging. In addition, white matter microstructural compromise may contribute to reduced processing speed in our sample of participants with history of neurotrauma. Findings of the current study add insight into the factors associated with complicated recovery from mild to moderate TBI.

Deep white matter hyperintensities affect verbal memory independent of PTSD symptoms in veterans with mild traumatic brain injury.

OBJECTIVE: Although white matter hyperintensity (WMH) pathology has been observed in the context of traumatic brain injury (TBI), the contribution of this type of macrostructural damage to cognitive and/or post-concussive symptomatology (PCS) remains unclear. METHODS: Sixty-eight Veterans (mTBI = 46, Military Controls [MCs] = 22) with and without history of mild TBI (mTBI) underwent structural MRI and comprehensive cognitive and psychiatric assessment. WMH volume was identified as deep (DWMH) or periventricular (PVWMH) on fluid-attenuated inversion recovery (FLAIR) images. RESULTS: Group analyses revealed that mTBI history was not associated with increased WMH pathology (p's > 0.05). However, after controlling for post-traumatic stress disorder (PTSD) and intracranial volume, DWMH was associated with reduced short-and long-delayed memory performance within the mTBI group (p's < 0.05). Additionally, after adjusting for PTSD and time since injury, regression analyses revealed that WMH was not associated with self-reported ratings of PCS (p's > 0.05) in the mTBI group. CONCLUSIONS: The results demonstrate that, in relatively young Veterans with mTBI, DWMH differentially and negatively affects memory performance above and beyond the effects of PTSD symptoms. The findings may help to clarify prior mixed results as well as offer focused treatment implications for Veterans with history of neurotrauma and evidence of macrostructural white matter damage.

Age exacerbates the negative effect of depression on executive functioning in racial and ethnic minorities.

Age and depression may interact to produce a "double jeopardy" for cognitive impairment, and executive functioning, in cognitively unimpaired aging. Few studies have considered middle age or the ethnoracial diversity of subjects, despite evidence of more severe cognitive outcomes in historically minoritized people. In this pilot study, we investigated the impact of age on depression-related cognitive impairment and the underlying brain volumes in middle-aged non-Hispanic White adults (116), and Hispanic and Black adults (60), with a total number of 176 adults. The result shows a significant interaction between age and depression for executive functioning, specifically for middle-aged Hispanic and Black adults, but not non-Hispanic White adults. Prefrontal cortex volumes, which were reduced in the Black and Hispanic compared to the non-Hispanic White adults, partially mediated the relationship between depression level and executive functioning, across age and ethnoracial group. Collectively, these results suggest that the negative impact of depression on executive functioning and Prefrontal cortex volumes integrity may be exacerbated by age and that historically minoritized people may be particularly sensitive to this double jeopardy.

Exercise: Just What the Doctor Ordered, But Why? Elucidating Mechanisms for Women's Increased High-Density Lipoprotein Benefit From Exercise and for the Health ABC Study.

High-density lipoprotein (HDL) is protective against cardiovascular disease. Exercise can increase HDL concentration, and some evidence suggests that this effect occurs more strongly in women than in men. Both HDL and exercise are associated with inflammation. We hypothesized a sex-by-exercise interaction on HDL level, whereby women would benefit from exercise more strongly than men, and tumor necrosis factor alpha and serum soluble tumor necrosis factor receptor-2 would mediate this relationship. This study included 2,957 older adult participants (1,520 women; 41% Black, 59% White; 73.6-years-old) from the Health, Aging, and Body Composition study. Regression models revealed a positive exercise-HDL relationship in women only (sex-by-exercise interaction: ß = 0.09, p = .013; exercise on HDL in women: ß = 0.07, p = .015), mediated by TNFα (axb = 0.15; CI: 0.01, 0.30), suggesting that exercise may increase HDL levels in women through reduced inflammation. Given that vascular risk contributes to Alzheimer's disease risk, findings have implications for sex differences in AD risk factors.

Cognition and Amyloid-ß in Older Veterans: Characterization and Longitudinal Outcomes of Data-Derived Phenotypes.

Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer's disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition. Objective: This study aimed to derive subgroups based on objective cognition, subjective cognitive decline (SCD), and amyloid burden, and then compare subgroups on clinical characteristics, biomarkers, and longitudinal change in functioning and global cognition. Methods: Cluster analysis of neuropsychological measures, SCD, and amyloid PET was conducted on 228 predominately male Vietnam-Era Veterans from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. Cluster-derived subgroups were compared on baseline characteristics as well as 1-year changes in everyday functioning and global cognition. Results: The cluster analysis identified 3 groups. Group 1 (n = 128) had average-to-above average cognition with low amyloid burden. Group 2 (n = 72) had the lowest memory and language, highest SCD, and average amyloid burden; they also had the most severe PTSD, pain, and worst sleep quality. Group 3 (n = 28) had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst AD biomarkers, and the fastest rate of everyday functioning and cognitive decline. CONCLUSIONS: Psychiatric and health factors likely contributed to Group 2's low memory and language performance. Group 3 was most consistent with biological AD, yet attention/executive function was the lowest score. The complexity of older Veterans' co-morbid conditions may interact with AD pathology to show attention/executive dysfunction (rather than memory) as a prominent early symptom. These results could have important implications for the implementation of AD-modifying drugs in older Veterans.

Pulse pressure and APOE ε4 dose interact to affect cerebral blood flow in older adults without dementia.

This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP - diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE ɛ4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.

Bilingual neurocognitive resiliency, vulnerability, and Alzheimer's disease biomarker correlates in Latino older adults enrolled in the Health and Aging Brain Study - Health Disparities (HABS-HD).

INTRODUCTION: The effects of bilingualism on neuropsychological test performance in bilinguals with and without cognitive impairment are not well-understood and are relatively limited by small sample sizes of Latinos. METHODS: Using analysis of covariance (ANCOVA), we explored patterns of cognitive performance and impairment across a large sample of community-dwelling bilingual and monolingual Latino older adults with (n = 180) and without (n = 643) mild cognitive impairment (MCI) enrolled in HABS-HD. RESULTS: Bilinguals demonstrated cognitive resiliency in the form of significantly better performance on the Trail Making Test and Digit Symbol Substitution Test, observed across the cognitively unimpaired and MCI groups. In contrast, bilinguals demonstrated cognitive vulnerability in the form of significantly poorer performance and higher impairment rates on phonemic fluency in the MCI phase, only. Follow-up analyses revealed less balanced bilinguals demonstrated poorer performance and higher impairment rates on this measure, supported by lower levels of plasma Aß 42/40. DISCUSSION: Patterns of cognitive performance and impairment differ as a function of bilingualism. Bilingualism must be considered when evaluating cognitive and biomarker outcomes in Latino older adults. Highlights: Latino bilinguals perform better on measures of processing speed and coding.Latino bilinguals with MCI demonstrate cognitive vulnerability in verbal fluency.Less balanced bilinguals demonstrate greatest vulnerability anchored by Aß 42/40.