Promoting diverse perspectives: Addressing health disparities related to Alzheimer's and all dementias.

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14-16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day of focused meetings centered on American Indian and Alaska Natives and on LGBTQIA+ populations. Over 1300 registrants attended discussions focused on the structural and systemic inequities experienced across diverse groups, as well as ways to investigate and address these inequities.

sPDGFRß and neuroinflammation are associated with AD biomarkers and differ by race: The ASCEND Study.

INTRODUCTION: There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants. METHODS: Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2. RESULTS: CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aß)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor ß (sPDGFRß) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aß40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRß and tau were significantly lower in B/AA than NHW. DISCUSSION: Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships. HIGHLIGHTS: Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals.

Mild Cognitive Impairment, But Not HIV Status, is Related to Reduced Awareness of Level of Cognitive Performance Among Older Adults.

OBJECTIVE: Self-assessment of cognitive abilities can be an important predictor of clinical outcomes. This study examined impairments in self-assessments of cognitive performance, assessed with traditional neuropsychological assessments and novel virtual reality tests among older persons with and without human immunodeficiency virus (HIV) and mild cognitive impairment (MCI). METHODS: One hundred twenty-two participants (82 persons with HIV; 79 MCI+) completed a traditional neuropsychological battery, DETECT virtual reality cognitive battery, and self-reported their general cognitive complaints, depressive symptoms, and perceptions of DETECT performance. Relationships between DETECT performance and self-assessments of performance were examined as were the correlations between general cognitive complaints and performance. These relations were evaluated across HIV and MCI status, considering the associations of depressive symptoms, performance, and self-assessment. RESULTS: We found no effect of HIV status on objective performance or self-assessment of DETECT performance. However, MCI+ participants performed worse on DETECT and traditional cognitive tests, while also showing a directional bias towards overestimation of their performance. MCI- participants showed a bias toward underestimation. Cognitive complaints were reduced compared to objective performance in MCI+ participants. Correlations between self-reported depressive symptoms and cognitive performance or self-assessment of performance were nonsignificant. CONCLUSIONS: MCI+ participants underperformed on neuropsychological testing, while overestimating performance. Interestingly, MCI- participants underestimated performance to approximately the same extent as MCI+ participants overestimated. Practical implications include providing support for persons with MCI regarding awareness of limitations and consideration that self-assessments of cognitive performance may be overestimated. Similarly, supporting older persons without MCI to realistically appraise their abilities may have clinical importance.

Intersectionality in Alzheimer's Disease: The Role of Female Sex and Black American Race in the Development and Prevalence of Alzheimer's Disease.

It is well known that vascular factors and specific social determinants of health contribute to dementia risk and that the prevalence of these risk factors differs according to race and sex. In this review, we discuss the intersection of sex and race, particularly female sex and Black American race. Women, particularly Black women, have been underrepresented in Alzheimer's disease clinical trials and research. However, in recent years, the number of women participating in clinical research has steadily increased. A greater prevalence of vascular risk factors such as hypertension and type 2 diabetes, coupled with unique social and environmental pressures, puts Black American women particularly at risk for the development of Alzheimer's disease and related dementias. Female sex hormones and the use of hormonal birth control may offer some protective benefits, but results are mixed, and studies do not consistently report the demographics of their samples. We argue that as a research community, greater efforts should be made to not only recruit this vulnerable population, but also report the demographic makeup of samples in research to better target those at greatest risk for the disease.

Is the association between cognitive disease progression and atrial fibrillation modified by sex?

INTRODUCTION: It is unclear if sex differences exist in cognitive disease progression in mild cognitive impairment (MCI) and dementia associated with atrial fibrillation (AF). METHODS: Using a variety of statistical methods, we examined sex differences between AF and neuropsychological tests and cognitive disease progression, using the National Alzheimer's Coordinating Center data (N = 43,630). RESULTS: AF is associated with higher odds of dementia (odds ratio [OR] 3.00, 95% confidence interval [CI] [1.22, 7.37] in women and MCI in women (OR 3.43, 95% CI [1.55, 7.55]) versus men. Women with AF and normal baseline cognition had a higher risk of disease progression (hazard ratio [HR] 1.26, 95% CI [1.06, 1.50]) from normal to MCI and from MCI to vascular dementia (HR3.27, 95% CI [1.89, 5.65]) than men with AF or men and women without AF. DISCUSSION: AF was associated with more rapid progression to MCI and dementia in women, but more research is needed to confirm these findings.

Higher systolic blood pressure in early-mid adulthood is associated with poorer cognitive performance in those with a dominantly inherited Alzheimer's disease mutation but not in non-carriers. Results from the DIAN study.

BACKGROUND: The Dominantly Inherited Alzheimer Network (DIAN) is a longitudinal observational study that collects data on cognition, blood pressure (BP), and other variables from autosomal-dominant Alzheimer's disease mutation carriers (MCs) and non-carrier (NC) family members in early to mid-adulthood, providing a unique opportunity to evaluate BP and cognition relationships in these populations. METHOD: We examined cross-sectional and longitudinal relationships between systolic and diastolic BP and cognition in DIAN MC and NC. RESULTS: Data were available from 528 participants, who had a mean age of 38 (SD = 11) and were 42% male and 61% MCs, at a median follow-up of 2 years. Linear-multilevel models found only cross-sectional associations in the MC group between higher systolic BP and poorer performance on language (ß = -0.181 [-0.318, -0.044]), episodic memory (-0.212 [-0.375, -0.049]), and a composite cognitive measure (-0.146 [-0.276, -0.015]). In NCs, the relationship was cross-sectional only and present for language alone. DISCUSSION: Higher systolic BP was cross-sectionally but not longitudinally associated with poorer cognition, particularly in MCs. BP may influence cognition gradually, but further longitudinal research is needed.

APOE and immunity: Research highlights.

INTRODUCTION: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODS: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry. RESULTS: During the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor α [TNFα]). DISCUSSION: This manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development.

Rationale and Design of the PARTNER Trial: Partnered Rhythmic Rehabilitation for Enhanced Motor-Cognition in Prodromal Alzheimer's Disease.

BACKGROUND: Functional decline in Alzheimer's disease (AD) is impacted by impaired ability to integrate and modulate complex cognitive and motor abilities, commonly known as motor-cognitive integration. Impaired motor-cognitive integration occurs in the early stages of AD, prodromal AD (pAD), and may precede other symptoms. Combined motor and cognitive training have been recommended for people with pAD and need to be better researched. Our data suggest that partnered rhythmic rehabilitation (PRR) improves motor-cognitive integration in older adults with cognitive impairment. PRR is an ideal intervention to simultaneously target cardiovascular, social, and motor-cognitive domains important to AD. OBJECTIVE/METHODS: We propose to conduct a 1-year Phase II, single-blind randomized controlled trial using PRR in 66 patients with pAD. Participants will be assigned to three months of biweekly sessions, followed by nine months of weekly sessions of PRR or group walking (WALK) with 1 : 1 allocation. Group walking in the control group will allow us to compare physical exercise alone versus the added benefit of the cognitively engaging elements of PRR. RESULTS/CONCLUSION: Using an intent-to-treat approach, this innovative pilot study will 1) Determine acceptability, safety, tolerability, and satisfaction with PRR; 2) Compare efficacy of PRR versus WALK for improving motor-cognitive integration and identify the most sensitive endpoint for a Phase III trial from a set of motor-cognitive, volumetric MRI, and cognitive measures. The study will additionally explore potential neural, vascular, and inflammatory mechanisms by which PRR affects pAD to derive effect size of these intermediary measures and aid us in estimating sample size for a future trial.

The effect of race and co-morbidities on Alzheimer's disease based on Medicare data.

INTRODUCTION: Alzheimer's disease (AD) incidence is thought to be higher among Black than White individuals. METHODS: We studied the US Medicare population from 2000 to 2018. Cox regression was used to determine the roles of race and co-morbidities for AD incidence. RESULTS: We studied 11,880,906 Medicare beneficiaries, with 774,548 AD cases. Hazard ratios (HRs) by increasing numbers of co-morbidities (1-7) were 1.51, 2.00, 2.55, 3.16, 2.89, 4.77, and 5.65. Among those with no co-morbidities, Black individuals had a lower rate than those who are White (HR = 0.69), while among those with one more co-morbidities, Black individuals had a higher rate (HR = 1.19). The presence of hypertension increased AD rates by 14% for White individuals, but 69% for those who are Black. DISCUSSION: More co-morbidities was strongly associated with higher AD rates. The higher rates for Black versus White individuals was apparent only for those with co-morbidities and appears driven both by more co-morbidities, and the greater effect of hypertension. HIGHLIGHTS: Black individuals have been shown to have higher Alzheimer's disease (AD) rates than those who are White. Some co-morbidities are known to increase AD risk. Among those In Medicare data with no co-morbidities, Black individuals have less risk than those who are White. Among those with co-morbidities, Black individuals have higher rates than those who are White. Hypertension results in a much stronger increase in AD risk for Black versus White individuals.

Inclusive Care Practices and Policies Among Sexual and Gender Minority Older Adults.

As the health care and well-being of sexual and gender minority (SGM; i.e., lesbian, gay, bisexual, and/or transgender or gender non-binary) people in the United States receive federal and local-level attention, SGM older adults and caregivers continue to be left out of important health policy and care conversations. The current article describes policy issues and affirmative strategies related to inclusive care practices among SGM older adults and caregivers. In addition to the broader policies considered related to health and well-being, we include a discussion of local-level policy strategies to mitigate discrimination and promote inclusive care for SGM older adults and caregivers. [Journal of Gerontological Nursing, 48(12), 6-15.].

Feasibility of the Savvy Caregiver Program for LGBTQ+ Caregivers of People Living with Alzheimer's Disease and Related Dementias.

Nearly 350,000 lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) adults in the U.S. are currently living with Alzheimer's disease and related dementias (ADRD). Informal caregivers face challenges impacting their ability to access and receive adequate and inclusive care for LGBTQ+ persons living with ADRD. The purpose of this study was to determine the feasibility and acceptability of the Savvy Caregiver Program for caregivers of LGBTQ+ individuals living with ADRD. Data for this secondary analysis come from caregivers (n = 17) who completed 6 sessions of the Savvy program. Caregivers were very satisfied with tailored program activities. Analyses of trends suggest non-significant increases in positive aspects of caregiving and decreases in caregiver burden and depressive symptoms. This is the first known study assessing the feasibility of the Savvy Caregiver Program for caregivers of LGBTQ+ individuals living with ADRD. Future research on the Savvy Caregiver Program for caregivers of LGBTQ+ people living with ADRD is needed.

Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia.

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-ß. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-ß is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.

Effect of renin-angiotensin system antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD) trial.

AIM: To determine whether antihypertensive medication (AHM) acting through the renin angiotensin system (RAS-AHM), compared with other AHM, can mitigate effects on cognitive function and risk for impairment in a population with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This secondary analysis of the randomized controlled Action for Health in Diabetes (Look AHEAD) study included 712 community-dwelling participants who were followed over 15 years. Logistic regression was used to relate RAS-AHM use to cognitive impairment, and linear regression was used to relate RAS-AHM use to domain-specific cognitive function after adjusting for potential confounders. RESULTS: A total of 563 individuals reported RAS-AHM use and 149 reported other-AHM use during the study. RAS-AHM users have college or higher education (53%), had higher baseline glycated haemoglobin (57 mmol/mol), and reported higher diabetes medication use (86%), while other-AHM users were more likely to be White (72%), obese (25%) and to have cardiovascular history (19%). RAS-AHM use was not associated with a reduced risk of dementia compared with other-AHM use. We did observe better executive function (Trail Making Test, part B, P < 0.04), processing speed (Digit Symbol Substitution Test, P < 0.004), verbal memory (Rey Auditory Verbal Learning Test-delayed recall, P < 0.005), and composite score (P < 0.008) among RAS-AHM users compared with other-AHM users. CONCLUSION: In this sample of adults with T2DM, free of dementia at baseline, we observed a slower decline in processing speed, executive function, verbal memory, and composite score among RAS-AHM users.

Sleep duration and biomarkers of inflammation in African American and white participants with a parental history of Alzheimer's disease.

Introduction: African Americans (AA)s have worse inflammation, worse sleep, and a greater incidence of Alzheimer's disease (AD) compared to whites; however, no studies have examined associations between biomarkers, sleep, and cognition, and differences by race. Methods: Seventy-six cognitively normal, middle aged (45-65 years) adults with a parental history of AD were included in this study. Associations between biomarkers (tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10], intercellular adhesion molecule-1 [ICAM-1],, and C-reactive protein [CRP]) and self-reported sleep or cognition measures, were assessed. Results: Average sleep duration was significantly lower for AA versus whites (average[SD]) in hours: 6.02(1.18) versus 7.23(0.91), P = .000004). We found a statistically significant association between plasma IL-10 and sleep duration (Spearman's ρ = 0.26, P = .04) and CSF ICAM-1 and sleep quality (Spearman's ρ = 0.30, P = .03). Discussion: Longer sleep duration is positively associated with plasma IL-10 levels irrespective of race. Sleep quality was positively associated with CSF ICAM-1 only in African Americans.

Barriers to accessing and engaging in healthcare as potential modifiers in the association between polyvictimization and mental health among Black transgender women.

BACKGROUND: Black transgender women endure pervasive polyvictimization (experiencing multiple forms of violence throughout the lifespan). Polyvictimization is associated with poor mental health. Black transgender women also face barriers in access to healthcare, but the extent that such barriers modify the association between polyvictimization and poor mental health has not been described using convergent mixed-methods analysis. METHODS: This convergent mixed-methods secondary analysis employs an intersectional lens and integrates two inter-related datasets to describe barriers to healthcare and the extent that such barriers modify the association between polyvictimization and mental health among Black transgender women. Investigators used survey data (n = 151 participants) and qualitative interview data (n = 19 participants) collected from Black transgender women (age 18 years and older) in Baltimore, MD and Washington, DC between 2016 and 2018. Analyses include thematic content analysis, bivariate analysis, joint display, and multivariate linear regression analysis examining mediation and moderation. RESULTS: Joint display illuminated three domains to describe how barriers to healthcare present among Black transgender women-Affordability, Accessibility, and Rapport and Continuity. Independent t-tests revealed significantly higher polyvictimization, Post Traumatic Stress Disorder (PTSD), and depression scores among participants who reported at least one barrier to healthcare (BHI) compared to those who reported no barriers. BHI significantly moderated and partially mediated the association between polyvictimization and PTSD symptom severity and BHI fully mediated the association between polyvictimization and depressive symptom severity-when accounting for age and location. DISCUSSION: Findings highlight the importance of access to healthcare in modifying the association between polyvictimization and PTSD and depression symptom severity among Black transgender women. Findings call for immediate interventions aimed at reducing barriers to healthcare and improved training for clinical providers serving Black transgender women.

Relationship between parental history of dementia, motor-cognitive and executive function performance in African American women.

People with parental history (PH) of Alzheimer's Disease (AD) and Alzheimer's Disease and related dementias (ADRD) are themselves at risk of developing dementia. ADRD are more prevalent in African Americans and women. A decline in executive function and motor-cognitive integration can cause an impaired performance of functional skills. The monitoring of cognitive and psychosocial function in individuals with a PH of ADRD is important for implementing interventions to delay or prevent ADRD diagnosis. This study compared 58 African American women (M age = 63.2 ± 7.2 years) with PH of ADRD (n = 34) versus without PH (NPH; n = 24) on the performance of motor-cognitive and executive function tasks, and mental and physical quality of life (QOL) using point biserial correlations and linear regression. Linear regression revealed no difference between participants with and without PH on motor-cognitive tests. However, compared to participants with NPH, participants with PH of ADRD performed significantly worse on the DKEFS (Delis Kaplan Executive Function System) Tower Test (PH: M = 9.9 ± 2.0; NPH: M = 11.5 ± 4.3; p = 0.046), had poorer mental QOL (PH: M = 46.8 ± 10.7; NPH: M = 52.8 ± 7.8 l; p = 0.007); and physical QOL (PH: M = 40.9 ± 9.3; NPH: M = 44.7 ± 8.6; p = 0.023). African American women at risk for ADRD may exhibit deficiencies in executive function and physical and mental quality of life before memory deficits meet the criterion for ADRD diagnosis. Motor-Cognitive tasks may be preserved. Executive function and mental and physical health-related QOL may be important targets for identifying individuals at increased risk for ADRD and developing appropriate rehabilitative interventions.

Advancing Gerontological Health Research With Sexual and Gender Minorities Across the Globe.

The current article presents results of a scoping review of international research on the health and health care needs of sexual and gender minority (SGM) older adults. Electronic databases and related resources were used to identify empirical and review studies published during the past 10 years. We reviewed 33 peer-reviewed articles from 19 countries. Findings were organized using the SGM Health Disparities Research Framework, which highlights factors at individual, interpersonal, community, and societal levels that impact health. Overall, historic and current environmental factors, including stigma, discrimination, and social exclusion, played an important role in SGM older adults' health, health care access, and use of related aging and social services. There is a critical need for training and future research, and health professionals are needed to advance gerontological health and health care research and improve the health and care of SGM older adults globally. [Journal of Gerontological Nursing, 48(4), 13-20.].

Approach and avoidant coping among black transgender women who have experienced violence: A qualitative analysis.

Black transgender women face nearly universal exposure to violence. Coping behaviors among cisgender women who have survived violence are well delineated; however, there are relatively few studies examining coping strategies for transgender women. The purpose of this qualitative study was to identify and characterize coping behaviors employed by Black transgender women (from Baltimore, MD and Washington, DC metropolitan areas) following an experience of violence. Secondary qualitative data analysis was conducted using framework analysis to explore narratives of 19 Black transgender women. Themes regarding avoidant and approach coping behaviors were developed within the context of existing literature. Approach coping behavior themes included: Help-Seeking, Seeking Guidance and Support, Self-Protecting Behavior, Positive Reappraisal, Self-Affirmation, Self-Care, Connection to a Higher Power, and Acceptance. Avoidant coping behavior themes included: Cognitive Avoidance, Substance, Alcohol, and Tobacco Use, Emotional Discharge, and Seeking Alternative Rewards. Participants employed similar coping behaviors as seen among cisgender women survivors of violence. However, several unique applications of approach coping mechanisms were identified including self-protecting behavior and self-affirming behavior. Culturally informed application of the identified coping behaviors can be taught and integrated into trauma-informed mental health interventions to promote strength and resilience among Black transgender women. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Subjective cognitive decline higher among sexual and gender minorities in the United States, 2015-2018.

INTRODUCTION: Subjective cognitive decline (SCD) represents self-reported problems with memory, a possible early sign of dementia. Little is known about SCD among sexual and gender minority (SGM) adults who identify as lesbian, gay, bisexual, and/or transgender or gender non-binary. METHODS: Data were weighted to represent population estimates from 25 states' 2015-2018 Behavioral Risk Factor Surveillance System to describe SCD in adults ≥45 years by SGM status. Logistic regression tested associations between demographic and health conditions. RESULTS: SCD prevalence was higher in SGM (15.7%; 95% confidence interval [CI]:13.1-18.2) than in non-SGM adults (10.5%; 95% CI:10.1-10.9; P < .0001). SGM adults with SCD were also more likely to report functional limitations due to SCD than non-SGM adults with SCD, 60.8% versus 47.8%, P = .0048. Differences in SCD by SGM status were attenuated after accounting for depression. DISCUSSION: Higher prevalence of SCD in SGM adults highlights the importance of ensuring inclusive screenings, interventions, care services, and resources for SGM adults.