And Related Dementias Risk Research Articles

THE EFFECTS OF LIFETIME EXPERIENCES OF HOMELESSNESS AND INCARCERATION ON COGNITIVE AGING

Abstract Alzheimer’s disease and related dementias (ADRD) remain a pressing health concern in the U.S., and this burden and access to care are unequally distributed across the population. The U.S. has one of the highest incarceration rates globally, which is also unequally distributed; and groups like veterans, formerly incarcerated people, and sexual and gender minorities (SGM) face high risk of homelessness. Homelessness and incarceration are potentially traumatic experiences in themselves. Both experiences are more likely among people with less formal education, less economic security, and racialized groups, even as they reduce educational and economic opportunities. Using data from the Health and Retirement Study (HRS; 1998–2016), we investigate whether self-reported lifetime experiences of homelessness and incarceration (including time spent incarcerated) are associated with cognitive functioning and risk of possible dementia. Multilevel modeling adjusted for age, education, and other demographic covariates revealed that lifetime experiences of homelessness and incarceration are associated with lower cognition (Homelessness: β=-1.231, p< .001; Incarceration: β=-0.929; p < .001), but slower aging-related declines (Homelessness-slopes: β=0.044, p<.001; Incarceration-slope β=0.041; p<.001), and homelessness moderated the impact of prior incarceration (β=-1.789; p<.001), but less-steep declines (β=0.092; p <.001). Homelessness and incarceration, independent of their other risk factors and associated harms, have associations with ADRD risk.

COGNITION IN CONTEXT: INVESTIGATING THE ROLE OF BUILT, SOCIAL, AND NATURAL ENVIRONMENTS IN COGNITIVE AGING

Abstract While a growing body of evidence points to potentially modifiable individual risk factors for Alzheimer’s Disease and Related Dementias (ADRD), the contexts in which people develop and navigate cognitive decline are largely overlooked. Geographic variation in ADRD rates suggest that environmental risk and protective factors may be important in cognitive aging and dementia caregiving. Community hazards are often heavily concentrated in underserved and underrepresented neighborhoods. This symposium aims to identify specific built, social, and natural environmental features associated with cognitive aging outcomes. The papers provide much-needed evidence on the role of neighborhoods and community networks for cognitive health and well-being among diverse older adults. First, Godina finds significant associations between neighborhood greenspace and microstructural indicators of brain health. Second, Westrick investigates the role of neighborhood disadvantage on long-term memory aging of older adults with and without a cancer diagnosis in later-life. Third, Finlay presents a new concept of Cognability to demonstrate which constellation of positive and negative neighborhood features may contribute most to healthy cognitive aging. Fourth, Nkimbeng identifies community networks and resources needed to inform dementia education and support care among African immigrants. Fifth, expert discussant Besser will share how these findings may inform upstream health promotion and reduce ADRD risk. She will discuss critical future research directions and methods to investigate environments of cognition. The symposium advances research assessing contexts of aging, and may inform public health and policy efforts to ameliorate community barriers and create more equitable opportunities to promote healthy aging in place.

GETTING TO BOLD USING SYSTEMIC EDUCATION, EVIDENCE, AND NETWORKS: HELPING GEORGIANS B-SEEN

Abstract The complex nature of Alzheimer’s disease and related dementias (ADRD) demands a comprehensive public health approach. Georgia is Building Our Largest Dementia infrastructure using Systemic Education, Evidence, and Networks (B-SEEN), with a vision for every Georgian – professional, patient, and care partner – to B-SEEN. The strength of Georgia’s B-SEEN project is the existing infrastructure. Leveraging this established network, Georgia has engaged in population-based efforts to increase impact in the dementia risk reduction, early diagnosis of ADRD, prevention and management of comorbidities and avoidable hospitalizations, and caregiving. These outcomes are being achieved by stakeholders disseminating evidence-based programs personalized to their community needs and the B-SEEN team leading coordinated activities that address dementia and support the promotion of brain health. This presentation will describe how ADRD risk reduction is integrated into a 159 county, de-centralized state and provides examples of several activities being implemented via Georgia extension, faith-based organizations, and dedicated partners.

ALZHEIMER'S DISEASE AND RELATED DEMENTIAS RISK AND PSYCHOSOCIAL HEALTH NEEDS OF OLDER ADULT IMMIGRANTS AND REFUGEES

Abstract To establish priorities for an intervention addressing Alzheimer’s Disease and Related Dementias (ADRD) risk among older adult immigrants and refugees from Afghanistan and the Middle-East and North Africa (MENA). A multi-methods Community-Based Collaborative Action Research design was employed to gather qualitative and quantitative data. Twenty community leaders and stakeholders participated in interviews and community needs survey responses of 124 ethnically diverse adults over age 55 were examined. We analyzed community needs survey data using descriptive statistics. A step-wise Thematic Analysis was used to analyze interview transcripts. A major theme and standout priority was identified: needing culturally-sensitive services and resources addressing social isolation among the elderly. Other psychosocial priorities included: accessibility needs, caregiving support, safety and end-of-life resources, digital literacy, and English language services. This study exemplifies a priority-setting partnership between clinician-researchers and refugee service providers. The priorities highlighted ADRD risk factors and guide the collaborative development of a community-based intervention.

REIMAGINING ALZHEIMER’S RESEARCH: ON THE ROAD TO NEW DISCOVERIES

Abstract Organized by the Alzheimer's disease and related dementias (ADRD) Interest Group, this symposium aims to highlight unique approaches to address 1) ADRD risk reductions through social and biological factors, and 2) quality of life of those with dementia. The first two presentations introduce remote communication technologies used for behavioral interventions, one for preventing social isolation and the resultant cognitive decline using video-chats by recruiting socially isolated older adults with mild cognitive impairment (MCI). The results of the recently completed randomized controlled trial provide evidence of a positive effect on cognition suggesting enhanced cognitive reserve. Another is for delivering a behavioral symptom intervention for community-dwelling persons with ADRD using telehealth. Researchers will highlight the feasibility, opportunities, and challenges of remote behavioral interventions. The third presentation focuses on micro-level communication between persons living with dementia and their family caregivers. By examining video-recorded home care observations, findings suggest caregiver education on positive interactions could facilitate more meaningful interaction with persons with ADRD. The fourth presentation explores pain among those with ADRD, a multifaceted phenomenon with health and functional consequences. Using the NHATS dataset, researchers show a continued need to detect and address pain in clinical settings particularly among persons with ADRD. The symposium concludes with a presentation using the CHARLS study to investigate correlations between inflammation or kidney-related metabolic biomarkers and cognition. Results provide longitudinal evidence of an association of kidney function and inflammation with cognitive test scores supporting the need to broaden dementia etiology research beyond the amyloid-cascade theory.

A PUBLIC HEALTH APPROACH TO ALZHEIMER’S DISEASE RISK REDUCTION: WHERE WE ARE AND WHERE WE’RE HEADED

Abstract A growing body of evidence has identified potential modifiable risk factors for Alzheimer’s disease and related dementias (ADRD). In 2021, the National Plan to Address Alzheimer's Disease (National Plan) included a new goal to promote healthy aging and address risk factors to help delay onset or slow progression of ADRD. Applying a robust public health approach to ADRD risk reduction can help achieve meaningful progress at the population level. The activities outlined in the Building Our Largest Dementia (BOLD) Infrastructure for Alzheimer’s Act (P.L. 115-406) are designed to create a uniform national public health infrastructure with a focus on various issues including risk reduction. The purpose of this session is to illustrate a public health approach to ADRD risk reduction, including its current status along with future directions and priorities. An overview of the National Plan’s new goal regarding ADRD risk reduction (McGuire) and data highlighting the current burden of key modifiable risk factors in the United States along with important disparities (Omura) will be presented. Holt will describe how ADRD risk reduction is integrated into the work of BOLD funding recipients, and Head will present experiences implementing public health activities that support ADRD risk reduction in the field along with successes and lessons learned. Finally, priorities and future directions for a public health approach to ADRD risk reduction will be presented from the perspective of the CDC’s Building Our Largest Dementia Infrastructure Public Health Center of Excellence on Dementia Risk Reduction (Baumgart).

The effect of a digital health coaching and health education protocol on cognition in adults at-risk for Alzheimer’s

Several modifiable lifestyle factors have been linked to cognitive ability and the risk of developing Alzheimer’s disease and related dementias (ADRD). Health coaching (HC) is an intervention that addresses lifestyle factors associated with cognition. The effectiveness of an HC protocol was evaluated and compared with a health education (HE) intervention, representing the current standard of care, in a sample of 216 adults between the ages of 45 and 75 years who were at-risk for developing ADRD. Outcomes examined were global cognition, neuropsychological cognition, and Alzheimer’s risk. HC participants received personalized coaching from a health coach focusing on nutrition, physical activity, sleep, stress, social engagement, and cognitive activity. HE participants received biweekly education materials focusing on the same modifiable lifestyle factors addressed by HC. Participants were assessed at baseline and again 4 months later. Self-reported global cognition scores improved only in the HC group (16.18 to 15.52, p = .03) and neuropsychological cognitive ability improved in the HE group (104.48 to 108.76, p < .001). When non-adherence in the HC group was accounted for, however, the mean change in neuropsychological score was similar between groups (p > .05), self-reported global cognition demonstrated an even larger mean improvement in the HC group (16.20 to 15.41, p = .01), and the HC group saw an improvement in ADRD protective risk score (− 10.39 to − 11.45, p = .007). These results indicate that HC and HE can both improve cognition, but HC may be more effective and may yield increased protection against ADRD risk.

Effects of Androgen Deprivation Therapy on Alzheimer's disease and Related Dementia Risk in the Million Veteran Program

AbstractBackgroundAndrogen deprivation therapy (ADT) for prostate cancer depletes circulating testosterone levels and has been shown to increase risk for Alzheimer’s disease (AD) and related dementias (ADRD). It is unclear whether ADT acts independently to increase ADRD risk, or whether effects of this treatment are exacerbated by the genetic risk for AD. We hypothesized that the effect of ADT on ADRD risk will be moderated by AD polygenic risk.MethodClinical and genetic data were analyzed from 87,060 United States Veterans, who had a diagnosis of prostate cancer and were participants in the Million Veterans Program (MVP) biorepository study. Clinical conditions, including diagnosis codes for ADRD, cancer, Charlson Comorbidity Index conditions, laboratory values (Gleason score, Prostate Specific Antigen levels), cancer treatments, and vital status were obtained from the Veterans Affairs (VA) longitudinal electronic health record data. A polygenic risk score (PRS) for AD was derived based on summary statistics from the Kunkle et al (2019) GWAS of Alzheimer’s disease. The impact of ADT on ADRD was assessed using a time‐varying Fine‐Gray competing risks regression. Death from any cause was considered as a competing event to the development of ADRD.ResultThere were 17,092 (19.6%) patients who received ADT. 72% of the cohort was of white/European ancestry. The average age at prostate cancer diagnosis was 66 years. The median duration of ADT was 360 days. ADT users were more likely to be African American, and had higher PSA levels and Gleason Scores. ADT exposure and the AD PRS each showed significant main effects on ADRD risk, HRs = 1.16 (95% CI: 1.04 ; 1.29) and 1.10 (95% CI: 1.06 ; 1.15) respectively; however, we did not observe a significant interaction effect. Sensitivity analyses indicate that the association was not confounded by including Gleason score, PSA level, income, or education, and results were not altered significantly by excluding or focusing on the effect of the APOE:E4 locus.ConclusionADT significantly increases risk of ADRD, independent of underlying AD genetic risk factors. Further research is necessary in order to determine the mechanism by which androgen depletion contributes to the pathophysiology of ADRD.

Multi‐ethnic differences in brain and biopsychosocial risk factors for ADRD in UK immigrants from the Middle East and North Africa (MENA)

AbstractBackgroundThe populations of the Middle East and North Africa countries (MENA) are predicted to contribute to the world’s sharpest increases in rates of Alzheimer’s disease and related dementias (ADRD) in the coming years (GBD 2022), yet this group is underrepresented in health studies. The UK Biobank provides one of the largest and well‐characterized datasets on aging immigrants in the UK. We compare risk factors for ADRDs between UK immigrants from MENA countries to those of immigrants from other countries.MethodImmigrants from MENA countries (N = 3557), India (N = 2959), Germany (N = 1103), and genetically‐determined British individuals (N = 1929) born outside of the UK in any of the three areas of interest were included in the study. There are multiple definitions of MENA: here, MENA was defined broadly to include the union of all included countries; Figure 1 highlights the distribution in this sample. We focused on variables associated with suboptimal brain aging and ADRD risk: APOE genotypes; education; an algorithmically defined diet quality score (Zhuang, 2021); BMI; incidence of parental death before 65 years; and the Townsend deprivation index (TDI) as a proxy of socioeconomic status (SES). Chi‐squared or Mann‐Whitney tests provided statistics on distribution discrepancies for categorical or continuous data, respectively. We also charted hippocampal volumes with age for the subset of each ethnic group who underwent neuroimaging.ResultFigure 2 highlights group demographics and distributions. Compared to all other groups (Figure 3), MENA groups had higher TDI (lower SES), lowest diet quality, and highest BMIs; these differences remained even in college educated individuals. MENA also reported a greater incidence of maternal deaths before age 65. German immigrants were more highly educated than all other groups. ApoE4 alleles were significantly less prevalent in MENA and Indian countries than groups of European ancestry (Figure 4). Hippocampal volumes, adjusted for intracranial volume, had similar age‐trends across groups.ConclusionMany ADRD risk factors differ substantially across different ethnic groups, even when the proportion with a college education is not different. It is imperative to understand underlying lifestyle and sociological factors associated with immigration, to provide adequate healthcare for all aging individuals.

Testing the Association Between Neighborhood Disadvantage and White Matter Hyperintensities

AbstractBackgroundSocial determinants of health—the conditions in the places where people live, learn, work, and play—have been shown to affect a broad range of health outcomes, including risk for Alzheimer’s disease and related dementias (ADRD). However, the biological mechanisms by which socio‐contextual factors increase risk for ADRD are poorly known. Higher levels of neighborhood disadvantage have been linked with increased cardiovascular disease (CVD) risk. CVD risk has been associated with white matter lesions known as white matter hyperintensities (WMH) because they produce increased signal on fluid‐attenuated inversion recovery (FLAIR) MRI scans. WMH have been associated with increased risk for stroke, cognitive decline, and dementia. We investigated whether greater neighborhood‐level disadvantage was associated with greater WMH volume.MethodParticipants (n = 804) were enrolled in the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center Clinical Core. MRI was performed at 3 T to acquire T2‐weighted FLAIR images which were then processed using the lesion prediction algorithm from the Lesion Segmentation Toolbox to measure WMH volume. Area Deprivation Index (ADI) distributions from the state of Wisconsin were used to create a dichotomous variable that compared the highest state‐ranked quintile (most disadvantaged neighborhoods) to the lowest 4 state‐ranked quintiles (least disadvantaged neighborhoods). Multiple linear regression tested ADI as a predictor of natural log‐transformed WMH volume. Age, sex, education, intracranial volume, MRI head coil, and study cohort were controlled.ResultFour percent (n = 33) of participants were identified as living in the most disadvantaged neighborhoods (see Table 1). The association between neighborhood‐level disadvantage and log‐transformed WMH volume was not statistically significant (see Table 2 and Figure 1).ConclusionNeighborhood disadvantage was not related to WMH volume in this study. This finding contrasts with previous studies demonstrating associations between increased neighborhood disadvantage and reduced cerebral and hippocampal volume (Hunt et al., 2020) and increased odds for AD neuropathology (Powell et al., 2020). Statistical power to assess the primary effect was likely limited by the small number of participants from the most disadvantaged neighborhoods. This illustrates the need for additional research and increased population‐representative recruitment from disadvantaged contexts for ADRD research studies.

Importance of accounting for regional differences in modifiable risk factors for Alzheimer’s disease and related dementias: The case for tailored interventions in California

AbstractBackgroundWe previously estimated that 37% of Alzheimer’s disease and related dementias (ADRD) cases in the U.S. may be attributable to modifiable risk factors, and that the most important risk factors differ based on race/ethnicity, but it’s not known whether national estimates generalize to specific states or regions. The aim of the present study was to (1) compare the proportion of ADRD cases that are potentially attributable to modifiable risk factors in California, to the U.S., overall and by sex and race/ethnicity, and (2) to estimate how many cases are potentially preventable by reducing the prevalence of key modifiable risk factors by 25%.MethodParticipants included adults ≥18 years from the California (n = 9,836) and the U.S. (n = 378,615). We calculated population attributable risks (PARs) using prevalence data from the national and California Behavioral Risk Factor Surveillance Survey (BRFSS) and relative risks from recent meta‐analyses. We estimated individual and combined PARs for ADRD in California and compared them to our U.S. estimates.ResultsIn California, overall, 29% of ADRD cases were potentially attributable to the combination of 8 modifiable risk factors evaluated in this study, compared to 37% in the U.S. The top 3 ADRD risk factors were the same in California and the U.S., but their relative importance differed (low education [CA:15%; U.S.:12%], midlife obesity [CA:15%; U.S.:17.7%], and physical inactivity (CA:10%; U.S.:12%). The combined PAR was lower in California compared to the U.S. in men (CA:28%; U.S.:36%) and Blacks (CA: 30%; U.S.:40%), but was similar in women and other race/ethnic groups. This was primarily due to lower risk factor prevalence within these groups. Low education was especially important in the Hispanic population (CA:30%; U.S.:26%). The total number of ADRD cases currently attributable to combined risk factors was 199,246 in California and 2,287,683 in the U.S. If the combined risk factors were reduced by 25%, we could potentially prevent approximately 40,665 cases in California and 445,737 in the U.S.ConclusionThe potential impact of modifiable ADRD risk factors differed in California and the U.S., overall and within sex and race/ethnic groups, highlighting the importance of tailoring dementia risk reduction campaigns.

Announcing the Vietnamese Insights into Aging Program (VIP)‐ The First Cohort Study of Cognitive Aging in Vietnamese Americans

AbstractBackgroundAsian Americans are the fastest growing racial population in the U.S; yet very little is known about their cognitive aging and Alzheimer’s disease and related dementias (ADRD) risk. Vietnamese Americans are the largest Southeast Asian group and are at high risk for health disparities. Unlike other large Asian subgroups, due to their sociopolitical history and experiences as refugees, Vietnamese Americans have faced a significant amount of adversity and trauma. As Vietnamese Americans age and their susceptibility to ADRD increases, their context may provide unique understanding in terms of within‐group heterogeneity and reveal key factors in ADRD and cognitive aging. The Vietnamese Insights into Aging Program (VIP) is the first longitudinal study of older Vietnamese Americans and addresses the dearth of ADRD research in this high‐disparity population. The goal is to obtain estimates of cognitive impairment and dementia in the community and identify ADRD risk (e.g., early life trauma) and protective (e.g., social support) factors in this understudied population.MethodWe will enroll 540 Vietnamese (age ≥65 years) across two sites in Northern California. Participants will be seen annually over 3 years to assess cognitive change over time. The following data will be collected: 1) a full neuropsychological battery; 2) an extensive interview about early life history and trauma as well as psychological and sociocultural factors, and 3) cardiovascular risk factors (hypertension, diabetes, smoking, etc.). Assessments will be conducted in Vietnamese and take place at a community partner site. In collaboration with local community partners, extensive community outreach and education were conducted prior to study recruitment.ResultVIP has developed a protocol for the bilingual Vietnamese assessments which has been further refined by scientists, staff, and VIP’s community advisory board, many of whom are bicultural and bilingual Vietnamese American. VIP currently has a waitlist of over 250 participants as of January 2022. We aim to complete Time 1 assessments of all 540 participants by Spring 2023.ConclusionInnovative research with older Vietnamese Americans provides a unique opportunity to refine research methodology and more fully delineate the factors that contribute to ADRD disparities in underserved populations.

Premature aging in co‐occurring Alcohol Use Disorder and Post‐Traumatic Stress Disorder from a functional connectome perspective

AbstractBackgroundPost‐Traumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD) may be associated with premature brain aging which increases the risk for Alzheimer’s Disease and Related Dementias (ADRD). While each disorder alone has been studied as a risk factor for ADRD, few studies have examined premature brain aging in co‐occurring PTSD/AUD. It is important to know whether co‐occurring PTSD/AUD may amplify ADRD risk. Consequently, the present study tested the hypothesis that, relative to healthy controls (HC), PTSD/AUD would show more pronounced premature brain aging than AUD alone.MethodA functional connectome approach was used to develop a model of healthy brain aging. The graph‐theory measure eigenvector centrality was calculated from resting state fMRI scans in 60 mid‐life HC (HC‐mid; mean age=56.9), 69 older adult HC (HC‐older; mean age = 74.1), 36 AUD (mean age=54.4), and 30 PTSD/AUD participants (mean age=55.7). AUD and PTSD/AUD diagnoses were determined by a structured clinical interview. Connectome node features that were most predictive of age in HC‐mid and HC‐older were used in predictive modeling with bootstrap aggregation. These features were from multiple cortical areas and resting state networks. The healthy aging model was transferred to the AUD and PTSD/AUD groups to estimate brain age. Estimated ages in AUD and PTSD/AUD were compared to the predicted age in HC‐mid and HC‐older using generalized linear mixed modeling (GLMM).ResultPredictive modeling in HC yielded an aggregate model with 49.5% accuracy in predicting age (p &lt; .0001), with some network features showing increases in eigenvector centrality with age and others showing decreases. After model transfer and correcting for age estimation bias, the GLMM yielded a main effect of diagnostic group (Wald c23=141.6, p &lt; .0001). Predicted age for PTSD/AUD was significantly higher (M=61.0) than HC‐mid (M=57.2; p=.048) but predicted age for AUD (M=59.9) was not different from HC‐mid (p=.133). HC‐older predicted age (M=74.1) was different from all other groups (p &lt; .0001).ConclusionIn this preliminary analysis, premature brain aging in PTSD/AUD was more pronounced than in AUD alone which may suggest greater vulnerability to AD‐like neurodegenerative processes that are manifest at the level of large‐scale network connectivity.

Improving risk indexes for Alzheimer's disease and related dementias for use in midlife.

Knowledge of a person’s risk for Alzheimer’s disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife (N = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age (β's from 0.16 to 0.22), white matter hyperintensities volume (β's from 0.16 to 0.19), hippocampal volume (β's from −0.08 to −0.11), tested cognitive deficits (β's from −0.36 to −0.49), everyday cognitive problems (β's from 0.14 to 0.38), and longitudinal cognitive decline (β's from −0.18 to −0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease.

A Review of Oxylipins in Alzheimer's Disease and Related Dementias (ADRD): Potential Therapeutic Targets for the Modulation of Vascular Tone and Inflammation.

There is now a convincing body of evidence from observational studies that the majority of modifiable Alzheimer’s disease and related dementia (ADRD) risk factors are vascular in nature. In addition, the co-existence of cerebrovascular disease with AD is more common than AD alone, and conditions resulting in brain ischemia likely promote detrimental effects of AD pathology. Oxylipins are a class of bioactive lipid mediators derived from the oxidation of long-chain polyunsaturated fatty acids (PUFAs) which act as modulators of both vascular tone and inflammation. In vascular cognitive impairment (VCI), there is emerging evidence that oxylipins may have both protective and detrimental effects on brain structure, cognitive performance, and disease progression. In this review, we focus on oxylipin relationships with vascular and inflammatory risk factors in human studies and animal models pertinent to ADRD. In addition, we discuss future research directions with the potential to impact the trajectory of ADRD risk and disease progression.

Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan.

As the population of older adults grows, so will the prevalence of aging-related conditions, including memory impairments and sleep disturbances, both of which are more common among women. Compared to older men, older women are up to twice as likely to experience sleep disturbances and are at a higher risk of cognitive decline and Alzheimer’s disease and related dementias (ADRD). These sex differences may be attributed in part to fluctuations in levels of female sex hormones (i.e., estrogen and progesterone) that occur across the adult female lifespan. Though women tend to experience the most significant sleep and memory problems during the peri-menopausal period, changes in memory and sleep have also been observed across the menstrual cycle and during pregnancy. Here, we review current knowledge on the interrelationships among female sex hormones, sleep, and memory across the female lifespan, propose possible mediating and moderating mechanisms linking these variables and describe implications for ADRD risk in later life.

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.

Association Between Specific Type 2 Diabetes Therapies and Risk of Alzheimer's Disease and Related Dementias in Propensity-Score Matched Type 2 Diabetic Patients.

ObjectiveWe sought to determine the impact of Type 2 Diabetes Mellitus (T2D) anti-hyperglycemic medications (A-HgM) on risk of Alzheimer’s disease (AD) and related dementias (ADRD) outcomes including vascular dementia, and non-AD dementia such as frontotemporal, Lewy body, and mixed etiology dementias.Research Design and MethodsThis retrospective cohort study used the US-based Mariner claims dataset. 1,815,032 T2D participants 45 years and older with records 6 months prior and at least 3 years after the diagnosis of T2D were included. Claims were surveyed for a diagnosis of AD and ADRD 12 months post T2D diagnosis. A propensity score approach was used to minimize selection bias. Analyses were conducted between January 1st and February 28th, 2021.ResultsIn this cohort study A-HgM exposure was associated with decreased diagnosis of AD (RR, 0.61; 95% CI, 0.59–0.62; p < 0.001), vascular dementia (RR, 0.72; 95% CI, 0.69–0.74; p < 0.001) and non-AD dementia (RR, 0.67; 95% CI, 0.66–0.68; p < 0.001). Metformin was associated with the greatest risk reduction and insulin with the least reduction in risk compared to patients not receiving A-HgM for ADRD risk. Of interest, patients with a diagnosis of AD, while either on metformin or insulin, were older in age and predominately female, than individuals on these drugs that did not develop AD. Mean (SD) follow-up was 6.2 (1.8) years.ConclusionAfter controlling for age, sex, and comorbidities, A-HgM in patients with T2D was associated with a reduced risk of AD and ADRD. These findings provide evidence in support of T2D as a risk factor for AD and ADRD and the beneficial impact of early and effective control of hyperglycemia to mitigate risk.

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.

Addressing Suicide Risk in Patients Living With Dementia During the COVID-19 Pandemic and Beyond.

Alzheimer’s disease and related dementias (ADRD) are progressive illnesses characterized by decline in cognitive function that impairs performing daily activities. People with ADRD are at an increased risk of suicide, especially those who have comorbid mental health conditions, have specific types of ADRD, or have been recently diagnosed. The coronavirus disease 2019 (COVID-19) pandemic has increased the distress of people with ADRD, a population also at increased risk of contracting the COVID-19 virus. In this article, we draw on a case study and use the Interpersonal Theory of Suicide to help describe the association between ADRD and suicide risk. Secondly, we call for new strategies to mitigate suicide risk in people living with ADRD during and beyond the current pandemic by using lessons learned from cancer care. Our goal is not to dictate solutions but rather to start the conversation by outlining a framework for future research aimed at preventing death by suicide in people with ADRD. Specifically, we draw on the updated Framework for Developing and Evaluating Complex Interventions to reflect on the complexity of the issue and to break it down into achievable parts to reduce the risk of suicidal behavior (ideation, plans, attempts) in those living with ADRD.