Consideration of sex and gender in Alzheimer's disease and related disorders from a global perspective.

Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. HIGHLIGHTS: The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.

Amplifying Their Voices: Advice, Guidance, and Perceived Value of Cancer Biobanking Research Among an Older, Diverse Cohort.

The use of biobanks may accelerate scientists' chances of developing cures and treatments that are tailored to individuals' biological makeup-a function of the precision medicine movement. However, given the underrepresentation of certain populations in biobanks, the benefits of these resources may not be equitable for all groups, including older, multi-ethnic populations. The objective of this study was to better understand older, multi-ethnic populations' (1) perceptions of the value of cancer biobanking research, (2) study design preferences, and (3) guidance on ways to promote and increase participation. This study was designed using a community-based participatory research (CBPR) approach and involved eight FGDs with 67 older (65-74 years old) black and white residents from Baltimore City and Prince George's County, MD. FGDs lasted between 90 and 120 min, and participants received a $25 Target gift card for their participation. Analysis involved an inductive approach in which we went through a series of open and axial coding techniques to generate themes and subthemes. Multiple themes emerged from the FGDs for the development of future cancer-related biobanking research including (1) expectations/anticipated benefits, (2) biobanking design preferences, and (3) ways to optimize participation. Overall, most participants were willing to provide biospecimens and favored cancer-related biobank. To increase participation of older, diverse participants in biobanking protocols, researchers need to engage older, diverse persons as consultants in order to better understand the value of biobanking research to individuals from the various populations. Scientists should also incorporate suggestions from the community on garnering trust and increasing comfort with study design.

Self-reported obstructive sleep apnea, amyloid and tau burden, and Alzheimer's disease time-dependent progression.

INTRODUCTION: Obstructive sleep apnea (OSA) is associated with Alzheimer's disease (AD) biomarkers in cognitively normal (CN) and mild cognitive impaired (MCI) participants. However, independent and combined effects of OSA, amyloid beta (Aß) and tau-accumulation on AD time-dependent progression risk is unclear. METHODS: Study participants grouped by biomarker profile, as described by the A/T/N scheme, where "A" refers to aggregated Aß, "T" aggregated tau, and "N" to neurodegeneration, included 258 CN (OSA-positive [OSA+] [A+TN+ n = 10, A+/TN- n = 6, A-/TN+ n = 10, A-/TN- n = 6 and OSA-negative [OSA-] [A+TN+ n = 84, A+/TN- n = 11, A-/TN+ n = 96, A-/TN- n = 36]) and 785 MCI (OSA+ [A+TN+ n = 35, A+/TN- n = 15, A-/TN+ n = 25, A-/TN- n = 16] and OSA- [A+TN+ n = 388, A+/TN- n = 28, A-/TN+ n = 164, A-/TN- n = 114]) older-adults from the Alzheimer's Disease Neuroimaging Initiative cohort. Cox proportional hazards regression models estimated the relative hazard of progression from CN-to-MCI and MCI-to-AD, among baseline OSA CN and MCI patients, respectively. Multi-level logistic mixed-effects models with random intercept and slope investigated the synergistic associations of self-reported OSA, Aß, and tau burden with prospective cognitive decline. RESULTS: Independent of TN-status (CN and MCI), OSA+/Aß+ participants were approximately two to four times more likely to progress to MCI/AD (P < .001) and progressed 6 to 18 months earlier (P < .001), compared to other participants combined (ie, OSA+/Aß-, OSA-/Aß+, and OSA-/Aß-). Notably, OSA+/Aß- versus OSA-/Aß- (CN and MCI) and OSA+/TN- versus OSA-/TN- (CN) participants showed no difference in the risk and time-to-MCI/AD progression. Mixed effects models demonstrated OSA synergism with Aß (CN and MCI [ß = 1.13, 95% confidence interval (CI), 0.74 to 1.52, and ß = 1.18, 95%CI, 0.82 to 1.54]) respectively, and with tau (MCI [ß = 1.31, 95% CI, 0.87 to 1.47]), P < .001 for all. DISCUSSION: OSA acts in synergism with Aß and with tau, and all three acting together result in synergistic neurodegenerative mechanisms especially as Aß and tau accumulation becomes increasingly abnormal, thus leading to shorter progression time to MCI/AD in CN and MCI-OSA patients, respectively.

Perceived Stress and Cognitive Decline in Different Cognitive Domains in a Cohort of Older African Americans.

BACKGROUND: Research indicates that stress is linked to cognitive dysfunction. However, few community-based studies have explored the relationship between perceived stress and cognitive decline, and fewer still have utilized cognitive domains rather than a global measure of cognition. OBJECTIVE: We examined the relation between perceived stress and the rate of decline in different cognitive domains. METHODS: Participants were older African Americans without dementia from the Minority Aging Research Study (MARS; N = 467, mean age: 73 years, SD: 6.1 years). A battery of 19 cognitive tests was administered at baseline and at annual intervals for up to 9 years (mean follow-up: 4 years), from which composite measures of global cognitive function and five specific cognitive domains were derived. The four-item Cohen's Perceived Stress Scale (PSS) was also administered at baseline. RESULTS: In linear mixed-effects models adjusted for age, sex, education, and vascular risk factors, higher perceived stress was related to faster declines in global cognition (ß = -0.019; SE: 0.008; t(1951) = -2.46), episodic memory (ß = -0.022; SE: 0.011; t(1954) = -1.99), and visuospatial ability (ß = -0.021; SE: 0.009; t(1939) = -2.38) all p < 0.05. Findings were similar in subsequent models adjusted for demographics, vascular diseases, and depressive symptoms. CONCLUSIONS: Results indicate that older African Americans with higher levels of perceived stress have more rapid declines in global cognition than those with lower levels, most notably for episodic memory and visuospatial ability.

Self-Reported Sleep in Older African Americans and White Americans.

OBJECTIVE: Assess the relationship of self-reported sleep quality and possible sleep disorders with disability in a racially diverse sample of community-dwelling older adults. METHODS: Participants included 943 non-demented older African Americans (n=452) and Whites (n=491) from two cohort studies, the Minority Aging Research Study (MARS) and the Rush Memory and Aging Project (MAP). Participants completed a 32-item questionnaire assessing sleep quality and the possible presence of three sleep disorders (sleep apnea, restless leg syndrome [RLS] and REM behavior disorder [RBD]). Disability was assessed with scales that quantified the ability to perform instrumental activities of daily living (IADL), basic activities of daily living (ADL), and physical mobility activities. RESULTS: More than half of the participants reported impaired sleep quality (51%), or the possible presence of at least one sleep disorder (57%; sleep apnea 44%, RLS 25% and RBD 7%). Sleep quality was rated poorer in African Americans, those with advancing age and fewer years of education (all P<.05). Only sleep apnea risk was associated with age (P<.02). In logistic regression models adjusted for age, sex, years of education, and race, both sleep quality and disorders were associated with disability (sleep quality with mobility disability (P<.001), sleep apnea risk with mobility disability and IADL disability (all P<.001) and RLS symptoms with mobility disability (P<.01). CONCLUSIONS: Results indicate that self-assessed impaired sleep is common in old age and is associated with disability.

Cytomegalovirus infection and risk of Alzheimer disease in older black and white individuals.

BACKGROUND: Human cytomegalovirus (CMV) is prevalent in older adults and has been implicated in many chronic diseases of aging. This study investigated the relation between CMV and the risk of Alzheimer disease (AD). METHODS: Data come from 3 cohort studies that included 849 participants (mean age [±SD], 78.6 ± 7.2 years; mean education duration [±SD], 15.4 ± 3.3 years; 25% black). RESULTS: A solid-phase enzyme-linked immunosorbent assay was used for detecting type-specific immunoglobulin G antibody responses to CMV and herpes simplex virus type 1 (HSV-1) measured in archived serum samples. Of 849 participants, 73.4% had serologic evidence of exposure to CMV (89.0% black and 68.2% white; P < .001). During an average of 5.0 years of follow-up, 93 persons developed AD. CMV seropositivity was associated with an increased risk of AD (relative risk, 2.15; 95% confidence interval, 1.42-3.27) and a faster rate of decline in global cognition (estimate [±standard error], -0.02 ± 0.01; P = .03) in models that controlled for age, sex, education duration, race, vascular risk factors, vascular diseases, and apolipoprotein ε4 level. Results were similar in black and white individuals for both incident AD and change in cognitive function and were independent of HSV-1 status. CONCLUSIONS: These results suggest that CMV infection is associated with an increased risk of AD and a faster rate of cognitive decline in older diverse populations.

Depressive symptoms and cognitive decline in older african americans: two scales and their factors.

OBJECTIVE: Depressive symptoms are common in older adults, and researchers have explored the possibility of a link between depressive symptoms and cognitive decline, with mixed results. Most studies use total score of the Center for Epidemiological Studies Depression Scale (CES-D) with predominately non-Hispanic white participants. We sought to examine the relationship between the four factors of the CES-D and cognitive decline in older African Americans. Generalizability was determined using the Geriatric Depression Scale (GDS) and its factors. METHODS: Participants without dementia from the Minority Aging Research Study (N = 298, mean age: 74 ± 5.68) underwent annual clinical evaluations (mean years: 5 ± 1.9), including depression assessment and cognitive testing, from which global and specific measures were derived. Cognitive decline was examined with linear mixed models adjusted for demographic variables and indicators of vascular risk. RESULTS: Total CES-D score was not related to baseline cognition or change over time, whereas total GDS score was related to decline in semantic and working memory. In examining CES-D factors, lack of positive affect (e.g., anhedonia) was related to decline in global cognition, episodic memory, and perceptual speed. Similarly for the GDS, anhedonia was associated with decline in semantic memory, and increased negative affect was associated with decline in global cognition and episodic, semantic, and working memory. CONCLUSION: Results suggest that depressive symptoms, particularly anhedonia and negative affect, are related to cognitive decline in older African Americans.

Differential effects of self-reported lifetime marijuana use on interleukin-1 alpha and tumor necrosis factor in African American adults.

It is unknown how lifetime marijuana use affects different proinflammatory cytokines. The purpose of the current study is to explore potential differential effects of lifetime marijuana use on interleukin-1 alpha (IL-1α) and tumor necrosis factor (TNF) in a community based sample. Participants included 168 African American adults (51 % female, median age = 47 years). Upon study entry, blood was drawn and the participants completed questions regarding illicit drug use history whose answers were used to create three groups: lifetime non-drug users (n = 77), lifetime marijuana only users (n = 46) and lifetime marijuana and other drug users (n = 45). In the presence of demographic and physiological covariates, non-drug users were approximately two times more likely (AOR 2.73, CI 1.18, 6.31; p = .03) to have higher TNF levels than marijuana only users. Drug use was not associated with IL-1α. The influence of marijuana may be selective in nature, potentially localizing around innate immunity and the induction of cellular death.

Association between interleukin-6 and neurocognitive performance as a function of self-reported lifetime marijuana use in a community based sample of African American adults.

The purpose of the current study was to determine if self-reported lifetime marijuana use moderates the relationship between interleukin-6 (IL-6) and neurocognitive performance. Participants included 161 African American adults (50.3% women), with a mean age of 45.24 (SD=11.34). Serum was drawn upon entry into the study and participants completed a demographic questionnaire, which included drug use history, and a battery of neuropsychological tests. Using multiple regression analyses and adjusting for demographic covariates, the interaction term comprised of IL-6 and self-reported lifetime marijuana use was significantly associated with poorer performance on the Written (ß=-.116; SE=.059; p=.049) and Oral trials (ß=-.143; SE=.062; p=.022) of the Symbol Digit Modalities Test, as well as the Trail Making Test trial A (ß=.157; SE=.071; p=.028). Current findings support previous literature, which presents the inverse relationship between IL-6 and neurocognitive dysfunction. The potential protective properties of marijuana use in African Americans, who are at increased risk for inflammatory diseases, are discussed.

Differences in internalizing symptoms between those with and without Cannabis Use Disorder among HBCU undergraduate students.

OBJECTIVE: To determine the differences in internalizing symptoms between those who met criteria for Cannabis Use Disorder (CUD) and those who did not in young adults attending a Historically Black College or University (HBCU). PARTICIPANTS: The sample included 619 undergraduate students, with 110 (18%) who met criteria for CUD. METHODS: Participants completed an online survey, which included demographic, anxious and depressive symptomatology, and substance use assessment. RESULTS: Those who met CUD criteria reported more depressive symptoms (M = 22.83 ± 10.74) and anxiety symptoms (M = 45.70 ± 12.82) than their non-CUD counterparts (M = 19.17 ± 10.58; M = 40.57 ± 14.11, respectively). CONCLUSION: Differences between those who met criteria for CUD and those who did not are consistent with previous literature and may aid in characterizing internalizing behaviors in HBCU students with CUD. Future research should examine the subgroups that may cycle through withdrawal symptoms, despite not having severe CUD. This subgroup may be at higher risk for psychopathology than their severe counterparts.

Neurocognitive functioning in comorbid insomnia and sleep apnea patients is better after positive airway pressure therapy, but worse after cognitive behavioral therapy for insomnia: exploratory analysis of cognitive outcomes from the Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea study.

STUDY OBJECTIVES: Neurocognitive impairments in comorbid insomnia and sleep apnea (COMISA) are not well documented. We explored neurocognitive functioning and treatment effects in individuals with COMISA as an ancillary study to a randomized clinical trial. METHODS: Participants with COMISA (n = 45; 51.1% female; mean age = 52.07 ± 13.29 years), from a 3-arm randomized clinical trial combining cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) concurrently (CBT-I+PAP) or sequentially, completed neurocognitive testing at baseline, and post-treatment. Using Bayesian linear mixed models, we estimated effects of CBT-I, PAP, or CBT-I+PAP, compared to baseline, and CBT-I+PAP compared to PAP on 12 metrics across five cognitive domains. RESULTS: This COMISA sample had worse neurocognitive performance at baseline than reported for insomnia, sleep apnea, and controls in the literature, though short-term memory and psychomotor speed performance appears intact. When comparing PAP to baseline, performance on all measures was better after treatment. Performance after CBT-I was worse compared to baseline, and only performance in attention/vigilance, executive functioning via Stroop interference and verbal memory was better with moderate-high effect sizes and moderate probability of superiority (61-83). Comparisons of CBT-I+PAP to baseline generated results similar to PAP and comparing CBT-I+PAP to PAP revealed superior performance in only attention/vigilance via psychomotor vigilance task lapses and verbal memory for PAP. CONCLUSIONS: Treatment combinations involving CBT-I were associated with poorer neurocognitive performance. These potentially temporary effects may stem from sleep restriction, a component of CBT-I often accompanied by initially reduced total sleep time. Future studies should examine long-term effects of individual and combined COMISA treatment pathways to inform treatment recommendations. CLINICAL TRIAL: This was an ancillary study from a clinical trial (Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS), which was preregistered at www.clinicaltrials.gov (NCT01785303)).

Cannabis use disorder severity and sleep quality among undergraduates attending a Historically Black University.

Nearly one third of Americans experience poor sleep, which is associated with numerous deleterious health outcomes. Poor sleep may be exacerbated when an individual attends college, as they experience drastic shifts in lifestyle and sleep patterns. Previous research suggests cannabis has therapeutic potential for sleep disorders but may also impair sleep quality long-term. However, no study has examined the differences in sleep quality within individuals who meet criteria for Cannabis Use Disorder (CUD). The purpose of the current study was to determine differences in sleep quality among undergraduate students who met criteria for mild CUD (n = 18), moderate CUD (n = 22), severe CUD (n = 16) and students who did not meet criteria for CUD (n = 244). Participants included 300 predominantly Black/African American undergraduate students (79% female), aged between 18 and 25 years. Each participant completed an online survey that included measures assessing sleep quality and CUD criteria. Employing analysis of covariance, the moderate CUD subgroup (M = 9.00, SD = 3.32) reported poorer sleep quality than individuals who did not meet criteria for CUD (M = 6.93, SD = 3.03). Interestingly, the severe CUD subgroup (M = 6.75, SD = 2.52) reported similar sleep quality to individuals who did not meet criteria for CUD (M = 6.93, SD = 3.03). Individuals meeting criteria for mild and moderate CUD reported the poorest sleep quality among the groups, suggesting a differentiation within CUD severity. Future research should assess withdrawal and cannabis use frequency among individuals who meet criteria for CUD to further elucidate disturbances in sleep quality among those with CUD.

Exploring the combined effects of sleep apnea and APOE-e4 on biomarkers of Alzheimer's disease.

Objective: We determined the interactive associations of apolipoprotein e4 (APOE-e4), and obstructive sleep apnea (OSA) on biomarkers of Alzheimer's disease and examined for racial/ethnic differences of this association. Methods: We used data from the National Alzheimer's Coordinating Center Uniform Dataset (NACC UDS). All participants undergo annual observations, including demographic survey, battery of neuropsychological tests, blood draw (with genotyping), and a clinical evaluation with medical and cognitive/dementia status assessment, while a subset of participants have cerebrospinal fluid (CSF) biomarkers and neuroimaging data. Biomarkers of AD were characterized as the presence of abnormally low amyloid in CSF, via validated Aß42 cut off protocols, and total segmented hippocampal volume, and volume of white matter hyper intensities (WMH). While clinical markers (to preview cognitive relationships) were characterized via the Montreal Cognitive Assessment (MOCA). Results: Biomarker and clinical marker data were derived from 1,387 participants at baseline (mean age = 69.73 ± 8.32; 58.6% female; 13.7% Black/African American), 18.4% of the sample had sleep apnea, and 37.9% were APOE-e4 carriers. Our results confirmed previous reports that OSA and APOE-e4 were independently associated with AD through abnormal levels of amyloid (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively), WMH volume (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively), and MOCA scores (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively). No significant interaction between OSA and APOE-e4 relative to amyloid emerged, however, race stratified analyses indicated the interaction of OSA and APOE-e4 and was significantly associated with WMH and hippocampal volume in Black/African American, but not white participants. Conclusion: OSA and APOE-e4 are interactively associated with WHM in Black/African Americans. This interaction may partially explicate increased levels of risk in this population.

A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance.

STUDY OBJECTIVES: This study examines the impact of cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea on nocturnal sleep and daytime functioning. METHODS: A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. One hundred eighteen individuals with comorbid insomnia and sleep apnea were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30 and 90 days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale, Epworth Sleepiness Scale, Functional Outcome of Sleep Questionnaire, and cognitive emotional measures. RESULTS: A main effect of time was found on diary-measured sleep parameters (decreased sleep onset latency and wake after sleep onset; increased total sleep time and sleep efficiency) and actigraphy-measured sleep parameters (decreased wake after sleep onset; increased sleep efficiency) and daytime functioning (reduced Epworth Sleepiness Scale, Flinders Fatigue Scale; increased Functional Outcome of Sleep Questionnaire) across all arms (all P < .05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured sleep onset latency and wake after sleep onset and increasing sleep efficiency, as well as improving Functional Outcome of Sleep Questionnaire and Flinders Fatigue Scale compared to self-monitoring. CONCLUSIONS: Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on self-reported sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS); URL: https://clinicaltrials.gov/ct2/show/NCT01785303; Identifier: NCT01785303. CITATION: Tu AY, Crawford MR, Dawson SC, et al. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. J Clin Sleep Med. 2022;18(3):789-800.

The Link between Obstructive Sleep Apnea and Neurocognitive Impairment: An Official American Thoracic Society Workshop Report.

There is emerging evidence that obstructive sleep apnea (OSA) is a risk factor for preclinical Alzheimer's disease (AD). An American Thoracic Society workshop was convened that included clinicians, basic scientists, and epidemiologists with expertise in OSA, cognition, and dementia, with the overall objectives of summarizing the state of knowledge in the field, identifying important research gaps, and identifying potential directions for future research. Although currently available cognitive screening tests may allow for identification of cognitive impairment in patients with OSA, they should be interpreted with caution. Neuroimaging in OSA can provide surrogate measures of disease chronicity, but it has methodological limitations. Most data on the impact of OSA treatment on cognition are for continuous positive airway pressure (CPAP), with limited data for other treatments. The cognitive domains improving with CPAP show considerable heterogeneity across studies. OSA can negatively influence risk, manifestations, and possibly progression of AD and other forms of dementia. Sleep-dependent memory tasks need greater incorporation into OSA testing, with better delineation of sleep fragmentation versus intermittent hypoxia effects. Plasma biomarkers may prove to be sensitive, feasible, and scalable biomarkers for use in clinical trials. There is strong biological plausibility, but insufficient data, to prove bidirectional causality of the associations between OSA and aging pathology. Engaging, recruiting, and retaining diverse populations in health care and research may help to decrease racial and ethnic disparities in OSA and AD. Key recommendations from the workshop include research aimed at underlying mechanisms; longer-term longitudinal studies with objective assessment of OSA, sensitive cognitive markers, and sleep-dependent cognitive tasks; and pragmatic study designs for interventional studies that control for other factors that may impact cognitive outcomes and use novel biomarkers.

Sleep Disturbance and Strain Among Caregivers of Persons Living With Dementia.

OBJECTIVE: The study objective was to examine predictors of sleep disturbance and strain among caregivers of persons living with dementia (PLWD). METHODS: This cross-sectional study utilized a sample of community-dwelling older adults and their family caregivers drawn from the 2017 National Health and Aging Trends Study and National Study of Caregiving. Multivariable logistic regression was used to assess the association between caregiver and PLWD characteristics and a composite measure of caregiving strain. High caregiving strain was defined as a total score of ≥ 5 on the 6 caregiving strain items (e.g., emotional difficulty, no time for self). We used multivariable proportional odds models to examine predictors of caregiver sleep-related outcomes (trouble falling back to sleep and interrupted sleep), after adjusting for other caregiver and PLWD factors. RESULTS: Of the 1,142 family caregivers, 65.2% were female, 15% were Black, and 14% were Hispanic. Average age was 60 years old. Female caregivers were more likely to report high level of strain compared to male caregivers (OR: 2.61, 95% CI = 1.56, 4.39). Compared to non-Hispanic Whites, non-Hispanic Black and Hispanic caregivers had reduced odds of reporting greater trouble falling back asleep [OR = 0.55, CI (0.36, 0.82) and OR = 0.56, CI (0.34, 0.91), respectively]. The odds of reporting greater trouble falling back asleep was significantly greater among caregivers with high blood pressure vs. caregivers without high blood pressure [OR = 1.62, CI (1.12, 2.33)]. CONCLUSION: In this cross-sectional study, caregivers with greater sleep difficulty (trouble falling back asleep) were more likely to report having high blood pressure. We found no racial/ethnic differences in interrupted sleep among caregivers to PLWD. These results suggest that interventions to improve sleep among caregivers to PLWD may decrease poor cardiovascular outcomes in this group.

Obesity and Race May Explain Differential Burden of White Matter Hyperintensity Load.

OBJECTIVE: Compared to European Americans, research indicates that African Americans have higher white matter hyperintensity (WMH) load; however, the clinical and biological bases underlying this higher burden are poorly understood. We hypothesize that obesity may explain differences in WMH between African and European Americans. METHODS: Participants enrolled in longitudinal brain aging studies (n=292; 61% Female; 92% European American; mean age=69.6±7.7) completed evaluations including medical exams, neuroimaging, and sociodemographic surveys. Overweight/obese status defined as body mass index ≥30 kg/m2, and WMH load, captured by FLAIR images, as sum of deep and periventricular volumes, scored using the Fazekas scale (0-6), WMH≥4 considered high. RESULTS: Logistic regression analyses, adjusted for age, sex, hypertension, and smoking history, indicated that age and interaction between race and obesity were significant predictors of WMH, demonstrating that obesity significantly moderated the relationship between race and WMH. Age independently increased the odds of high WMH by 16% (OR=1.16, 95% CI=1.09-1.23, p<0.001). Stratified analysis indicates that older European Americans had increased WMH (OR=1.17, 95% CI=1.09-1.23, p<0.001), while obese African Americans had increased WMH (OR=27.65, 95% CI=1.47-519.13, p<0.05). In a case controlled subgroup matched by age, sex, and education (n=48), African Americans had significantly higher WMH load (27% vs 4%, Χ 2=5.3, p=0.02). CONCLUSION: Results denote that age predicted WMH among European Americans, while obesity predicted WMH among African Americans. Matched sample analyses indicate that obesity increases the odds of WMH, though more pronounced in African Americans. These findings suggest that obesity may explain the differential burden of white matter hyperintensity load, signifying public health and clinical importance.

Interactive Associations of Neuropsychiatry Inventory-Questionnaire Assessed Sleep Disturbance and Vascular Risk on Alzheimer's Disease Stage Progression in Clinically Normal Older Adults.

Background: To determine whether sleep disturbance (SD) and vascular-risk interact to promote Alzheimer's disease (AD) stage-progression in normal, community-dwelling older adults and evaluate their combined risk beyond that of established AD biomarkers. Methods: Longitudinal data from the National Alzheimer's Coordinating Center Uniform-Dataset. SD data (i.e., SD+ vs. SD-), as characterized by the Neuropsychiatric Inventory-Questionnaire, were derived from 10,600 participants at baseline, with at-least one follow-up visit. A subset (n = 361) had baseline cerebrospinal fluid (CSF) biomarkers and MRI data. The Framingham heart study general cardiovascular disease (FHS-CVD) risk-score was used to quantify vascular risk. Amnestic mild cognitive impairment (aMCI) diagnosis during follow-up characterized AD stage-progression. Logistic mixed-effects models with random intercept and slope examined the interaction of SD and vascular risk on prospective aMCI diagnosis. Results: Of the 10,600 participants, 1,017 (9.6%) reported SD and 6,572 (62%) were female. The overall mean (SD) age was 70.5 (6.5), and follow-up time was 5.1 (2.7) years. SD and the FHS-CVD risk-score were each associated with incident aMCI (aOR: 1.42 and aOR: 2.11, p < 0.01 for both). The interaction of SD and FHS-CVD risk-score with time was significant (aOR: 2.87, p < 0.01), suggesting a synergistic effect. SD and FHS-CVD risk-score estimates remained significantly associated with incident aMCI even after adjusting for CSF (Aß, T-tau, P-tau) and hippocampal volume (n = 361) (aOR: 2.55, p < 0.01), and approximated risk-estimates of each biomarker in the sample where data was available. Conclusions: Clinical measures of sleep and vascular risk may complement current AD biomarkers in assessing risk of cognitive decline in older adults.