A systematic review/meta-analysis of prevalence and incidence rates illustrates systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research.

We investigate Alzheimer's disease and related dementia (ADRD) prevalence, incidence rate, and risk factors in individuals racialized as Asian and/or Asian-American and assess sample representation. Prevalence, incidence rate, risk factors, and heterogeneity of samples were assessed. Random-effects meta-analysis was conducted, generating pooled estimates. Of 920 records across 14 databases, 45 studies were included. Individuals racialized as Asian and/or Asian-American were mainly from Eastern and Southern Asia, had higher education, and constituted a smaller sample relative to non-Hispanic white cohorts. The average prevalence was 10.9%, ranging from 0.4% to 46%. The average incidence rate was 20.03 (12.01-33.8) per 1000 person-years with a range of 75.19-13.59 (12.89-14.33). Risk factors included physiological, genetic, psychological, behavioral, and social factors. This review underscores the systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research and the need for inclusive approaches accounting for culture, language, and immigration status. HIGHLIGHTS: There is considerable heterogeneity in the prevalence of ADRD among studies of Asian-Americans. There is limited data on group-specific risk factors for ADRD among Asian-Americans. The average prevalence of (ADRD) among Asian-Americans was found to be 7.4%, with a wide range from 0.5% to 46%.

Recruiting a prospective community cohort to study Alzheimer's disease and structural and social determinants of health among adults racialized as Black: The ARCHES cohort.

INTRODUCTION: This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study. METHODS: Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood-based biomarker collection, optional one-time magnetic resonance imaging (MRI) scan, and community workshop. RESULTS: Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking engagements were the most effective. DISCUSSION: The systemic underrepresentation of Black participants in AD research impacts the ability to generalize research findings and determine the effectiveness and safety of disease-modifying treatments. Research to slow, stop, or prevent AD remains a top priority but requires diversity in sample representation. Highlights: Provide flexible appointments in the evening or weekends, offering transportation assistance, and allowing participants to complete study visits at alternative locations, such as senior centers or community centers.Continuously monitor and analyze recruitment data to identify trends, challenges, and opportunities for improvement.Implement targeted strategies to recruit participants who are underrepresented based on sex, gender, or education to increase representation.Diversify the research team to include members who reflect the racial and cultural backgrounds of the target population, to enhance trust and rapport with prospective participants.

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.

Is Multidimensional Poverty Associated to Dementia Risk? The Case of Older Adults in Pakistan.

Background and Objectives: Multidimensional poverty is associated with dementia. We aimed at establishing this association in Pakistan. Research Design and Methods: A cross-sectional study was conducted in Punjab and Sindh, Pakistan, between March 30, 2002, and August 22, 2022, among adults aged 50 and older. Multidimensional poverty measures were composed of 6 dimensions and 15 indicators. Poverty was compared between adults with and without dementia using the Rowland Universal Dementia Assessment Scale, adjusting for sex, age, marital status, and household size. Associations between dementia and poverty were investigated using a multivariate logistic regression model. Results: We found that 594 (72.7%), 171 (20.9%), and 52 (6.4%) had no, mild, and moderate-to-severe dementia, respectively. More women than men had dementia (11.4% vs 2.9%). Approximately 40.4% of adults with dementia were found to be deprived in 4 or more dimensions compared to 8.9% without dementia, and the difference in multidimensional poverty between them was 348.6%. Education, health, living conditions, and psychological well-being were the main contributors to poverty. Poverty in 4 or more dimensions was strongly associated with dementia (odds ratio [OR], 5.02; 95% confidence interval [CI], 2.07-12.16) after adjusting for sex, marital status, age, and household size, with greater odds for older women (OR, 2.02; 95% CI, 1.41-2.90). Discussion and Implications: Our findings suggest that early improvement in social determinants of health through targeted structural policies may prevent dementia later in life. Improving access to free, quality education, health care including mental health care and basic living standards, and employment should reduce the collective risk of dementia.

Baseline levels and longitudinal rates of change in plasma Aß42/40 among self-identified Black/African American and White individuals.

Objective: The use of blood-based biomarkers of Alzheimer disease (AD) may facilitate access to biomarker testing of groups that have been historically under-represented in research. We evaluated whether plasma Aß42/40 has similar or different baseline levels and longitudinal rates of change in participants racialized as Black or White. Methods: The Study of Race to Understand Alzheimer Biomarkers (SORTOUT-AB) is a multi-center longitudinal study to evaluate for potential differences in AD biomarkers between individuals racialized as Black or White. Plasma samples collected at three AD Research Centers (Washington University, University of Pennsylvania, and University of Alabama-Birmingham) underwent analysis with C2N Diagnostics' PrecivityAD™ blood test for Aß42 and Aß40. General linear mixed effects models were used to estimate the baseline levels and rates of longitudinal change for plasma Aß measures in both racial groups. Analyses also examined whether dementia status, age, sex, education, APOE ε4 carrier status, medical comorbidities, or fasting status modified potential racial differences. Results: Of the 324 Black and 1,547 White participants, there were 158 Black and 759 White participants with plasma Aß measures from at least two longitudinal samples over a mean interval of 6.62 years. At baseline, the group of Black participants had lower levels of plasma Aß40 but similar levels of plasma Aß42 as compared to the group of White participants. As a result, baseline plasma Aß42/40 levels were higher in the Black group than the White group, consistent with the Black group having lower levels of amyloid pathology. Racial differences in plasma Aß42/40 were not modified by age, sex, education, APOE ε4 carrier status, medical conditions (hypertension and diabetes), or fasting status. Despite differences in baseline levels, the Black and White groups had a similar longitudinal rate of change in plasma Aß42/40. Interpretation: Black individuals participating in AD research studies had a higher mean level of plasma Aß42/40, consistent with a lower level of amyloid pathology, which, if confirmed, may imply a lower proportion of Black individuals being eligible for AD clinical trials in which the presence of amyloid is a prerequisite. However, there was no significant racial difference in the rate of change in plasma Aß42/40, suggesting that amyloid pathology accumulates similarly across racialized groups.

Disparate Dementia Risk Factors Are Associated with Cognitive Impairment and Rates of Decline in African Americans.

OBJECTIVE: This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging. METHODS: Modifiable dementia risk factors and their associations with cognitive impairment and cognitive decline were determined in community-dwelling African American (AA; n = 261) and non-Hispanic White (nHW; n = 193) participants who completed ≥2 visits at the Mayo Clinic Alzheimer Disease Research Center in Jacksonville, Florida. Risk factors and their associations with cognitive impairment (global Clinical Dementia Rating [CDR] ≥ 0.5) and rates of decline (CDR Sum of Boxes) in impaired participants were compared in AA and nHW participants, controlling for demographics, APOE ɛ4 status, and Area Deprivation Index. RESULTS: Hypertension, hypercholesterolemia, obesity, and diabetes were overrepresented in AA participants, but were not associated with cognitive impairment. Depression was associated with increased odds of cognitive impairment in AA (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 2.13-8.67) and nHW participants (OR = 2.79, 95% CI = 1.21-6.44) but uniquely associated with faster decline in AA participants (ß = 1.71, 95% CI = 0.69-2.73, p = 0.001). Fewer AA participants reported antidepressant use (9/49, 18%) than nHW counterparts (57/78, 73%, p < 0.001). Vitamin B12 deficiency was also associated with an increased rate of cognitive decline in AA participants (ß = 2.65, 95% CI = 0.38-4.91, p = 0.023). INTERPRETATION: Modifiable dementia risk factors are common in AA and nHW participants, representing important risk mitigation targets. Depression was associated with dementia in AA and nHW participants, and with accelerated declines in cognitive function in AA participants. Optimizing depression screening and treatment may improve cognitive trajectories and outcomes in AA participants. ANN NEUROL 2024;95:518-529.

Associations Between Plasma, Imaging, and Cerebrospinal Fluid Biomarkers with Driving Behavior and Cognitive Tests: Implications for Biomarker Usefulness.

Background: Declines in instrumental activities of daily living like driving are hallmarks sequelae of Alzheimer's disease (AD). Although driving has been shown to be associated with traditional imaging and cerebrospinal fluid (CSF) biomarkers, it is possible that some biomarkers have stronger associations with specific aspects of driving behavior. Furthermore, associations between newer plasma biomarkers and driving behaviors are unknown. Objective: This study assessed the extent to which individual plasma, imaging, and CSF biomarkers are related to specific driving behaviors and cognitive functions among cognitively normal older adults. Methods: We analyzed naturalistic driving behavior from cognitively healthy older drivers (N = 167, 47% female, mean age = 73.3 years). All participants had driving, clinical, and demographic data and completed biomarker testing, including imaging, CSF, and/or plasma, within two years of study commencement. Results: AD biomarkers were associated with different characteristics of driving and cognitive functioning within the same individuals. Elevated levels of plasma Aß40 were associated with more speeding incidents, higher levels of CSF tau were related to shorter duration of trips, and higher CSF neurofilament light chain values were associated with traveling shorter distances, smaller radius of gyration, and fewer trips at night. We demonstrated that plasma, like CSF and imaging biomarkers, were helpful in predicting everyday driving behaviors. Conclusions: These findings suggest that different biomarkers offer complementary information with respect to driving behaviors. These distinct relationships may help in understanding how different biological changes that occur during the preclinical stage of AD can impact various sensorimotor and cognitive processes.

Medication and Road Test Performance Among Cognitively Healthy Older Adults.

Importance: Older adults are increasingly prescribed medications that have adverse effects. Prior studies have found a higher risk of motor vehicle crashes to be associated with certain medication use. Objective: To determine whether specific medication classes were associated with performance decline as assessed by a standardized road test in a community sample of cognitively healthy older adults, to evaluate additional associations of poor road test performance with comorbid medical conditions and demographic characteristics, and to test the hypothesis that specific medication classes (ie, antidepressants, benzodiazepines, sedatives or hypnotics, anticholinergics, antihistamines, and nonsteroidal anti-inflammatory drugs or acetaminophen) would be associated with an increase in risk of impaired driving performance over time. Design, Setting, and Participants: This was a prospective cohort study of 198 cognitively healthy adults 65 years and older with a valid driver's license who were followed up annually, with rolling enrollment. Data were collected from participants in St Louis, Missouri, and neighboring Illinois who were enrolled in the Knight Alzheimer's Disease Research Center. Data were collected from August 28, 2012, to March 14, 2023, and analyzed from April 1 to 25, 2023. Participants with healthy cognition, defined as a Clinical Dementia Rating score of 0 at baseline and subsequent visits, who had available clinical, neuropsychological, road tests, and self-reported medication data were included. Exposure: Potentially driver-impairing medication use. Main Outcomes and Measures: The primary outcome measure was performance on the Washington University Road Test (pass or marginal/fail). Multivariable Cox proportional hazards models were used to evaluate associations between potentially driver-impairing medication use and road test performance. Results: Of the 198 included adults (mean [SD] baseline age, 72.6 [4.6] years; 87 female [43.9%]), 70 (35%) received a marginal/fail rating on the road test over a mean (SD) follow-up of 5.70 (2.45) years. Any use of antidepressants (adjusted hazard ratio [aHR], 2.68; 95% CI, 1.69-4.71), serotonin and norepinephrine reuptake inhibitors (aHR, 2.68; 95% CI, 1.54-4.64), sedatives or hypnotics (aHR, 2.70; 95% CI, 1.40-5.19), or nonsteroidal anti-inflammatory drugs (aHR, 2.72; 95% CI, 1.31-5.63) was associated with an increase in risk of receiving a marginal/fail rating on the road test compared with control individuals. Conversely, participants taking lipid-lowering agents had a lower risk of receiving a marginal/fail rating compared to control individuals. There were no statistically significant associations found between anticholinergic or antihistamines and poor performance. Conclusions and Relevance: In this prospective cohort study, specific medication classes were associated with an increase in risk of poor road test performance over time. Clinicians should consider this information and counsel patients accordingly when prescribing these medications.

Addressing the Complex Driving Needs of an Aging Population.

This JAMA Insights reviews the complex driving needs of older individuals and how clinicians can help address these needs, including recommending use of supplemental technology, assessing fitness to drive, and reviewing medications that may impair driving ability.

Age-Specific Barriers and Facilitators to Research Participation Amongst African Americans in Observational Studies of Memory and Aging.

BACKGROUND: Black/African Americans experience a high burden of Alzheimer disease and related dementias yet are critically underrepresented in corresponding research. Understanding barriers and facilitators to research participation among younger and older African Americans is necessary to inform age-specific strategies to promote equity in studies of early- and late-onset neurodegenerative diseases. STUDY DESIGN: Survey respondents (n = 240) rated barriers and facilitators of research participation. Age-specific differences were evaluated using nonparametric Kruskal-Wallis tests across respondents aged 18-44 years (n = 76), 45-64 years (n = 83), and ≥ 65 years (n = 81). Strategies to mitigate barriers and promote facilitators were further explored via community-based focus groups. Pooled frequency of common themes discussed in focus groups were evaluated and compared across different ages including ≥ 45 years, ≥ 65 years, and mixed ages ≥ 45 years. RESULTS: Younger respondents (aged 18-44 and 45-64 years) expressed a greater need for flexibility in when, where, and how research testing takes place versus adults ≥ 65 years. Focus groups emphasized long-lasting consequences of systemic racism and the need to build and foster trust to resolve barriers and promote research engagement amongst African Americans. DISCUSSION: Age-specific strategies are needed to increase engagement, address recruitment disparities, and promote retention of African American participants in memory and aging studies across the lifespan.

Neuropsychiatric Symptoms and Alzheimer Disease Biomarkers Independently Predict Progression to Incident Cognitive Impairment.

OBJECTIVES: To investigate the effect of neuropsychiatric symptoms and depression symptoms, respectively, and Alzheimer disease (AD) biomarkers (cerebrospinal fluid [CSF] or Positron Emission Tomography [PET] imaging) on the progression to incident cognitive impairment among cognitively normal older adults. DESIGN: Prospective, observation, longitudinal study. SETTING: Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine. PARTICIPANTS: Older adults aged 65 and above who participated in AD longitudinal studies (n = 286). MEASUREMENTS: CSF and PET biomarkers, Clinical Dementia Rating (CDR), Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS: Participants had an average follow-up of eight years, and 31 progressed from CDR 0 to CDR >0. After adjusting for sex, age, and education in the Cox proportional hazards survival models, neuropsychiatric symptoms as a time-dependent covariate was statistically significant in the three CSF (Aß42/Aß40, t-Tau/Aß42, p-Tau/Aß42) PET imaging models (HR = 1.33-1.50). The biomarkers were also significant as main effects (HR = 2.00-4.04). Change in depression symptoms was not significant in any models. The interactions between biomarkers and neuropsychiatric symptoms and depression were not statistically significant. CONCLUSIONS: Changes in neuropsychiatric symptoms increase the risk of progression to cognitive impairment among healthy, cognitively normal adults, independent of AD biomarkers. Routine assessment of neuropsychiatric symptoms could provide valuable clinical information about cognitive functioning and preclinical disease state.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

Neuroinflammation: A Modifiable Pathway Linking Obesity, Alzheimer's disease, and Depression.

Obesity, depression and Alzheimer's disease (AD) are three major interrelated modern health conditions with complex relationships. Early-life depression may serve as a risk factor for AD, while late-life depression may be a prodrome of AD. Depression affects approximately 23% of obese individuals, and depression itself raises the risk of obesity by 37%. Mid-life obesity independently increases AD risk, while late-life obesity, particularly metabolically healthy obesity, may offer protection against AD pathology. Chronic inflammation serves as a key mechanism linking obesity, AD, and depression, encompassing systemic inflammation from metabolic disturbances, immune dysregulation through the gut microbiome, and direct interactions with amyloid pathology and neuroinflammation. In this review, we explore the biological mechanisms of neuroinflammation in relation to obesity, AD, and depression. We assess the efficacy of therapeutic interventions targeting neuroinflammation and discuss current and future radiological imaging initiatives for studying neuroinflammation. By comprehending the intricate interplay among depression, obesity, and AD, especially the role of neuroinflammation, we can advance our understanding and develop innovative strategies for prevention and treatment.

Design and feasibility of an Alzheimer's disease blood test study in a diverse community-based population.

INTRODUCTION: Alzheimer's disease (AD) blood tests are likely to become increasingly important in clinical practice, but they need to be evaluated in diverse groups before use in the general population. METHODS: This study enrolled a community-based sample of older adults in the St. Louis, Missouri, USA area. Participants completed a blood draw, Eight-Item Informant Interview to Differentiate Aging and Dementia (AD8® ), Montreal Cognitive Assessment (MoCA), and survey about their perceptions of the blood test. A subset of participants completed additional blood collection, amyloid positron emission tomography (PET), magnetic resonance imaging (MRI), and Clinical Dementia Rating (CDR® ). RESULTS: Of the 859 participants enrolled in this ongoing study, 20.6% self-identified as Black or African American. The AD8 and MoCA correlated moderately with the CDR. The blood test was well accepted by the cohort, but it was perceived more positively by White and highly educated individuals. DISCUSSION: Studying an AD blood test in a diverse population is feasible and may accelerate accurate diagnosis and implementation of effective treatments. HIGHLIGHTS: A diverse group of older adults was recruited to evaluate a blood amyloid test. The enrollment rate was high and the blood test was well accepted by participants. Cognitive impairment screens have moderate performance in a diverse population. Alzheimer's disease blood tests are likely to be feasible for use in real-world settings.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Multidimensional poverty is associated with dementia among adults in Afghanistan.

Background: Multidimensional poverty is associated with dementia, but no evidence is available for countries in conflict. Methods: A cross-sectional study was conducted in two provinces of Afghanistan between February 15th 2022 and April 20th 2022 among adults age 50 and older. Multidimensional poverty included six dimensions of well-being and 16 indicators of deprivation. The Rowland Universal Dementia Assessment Scale measured dementia. Poverty between adults with and without dementia was examined, adjusting for sex. Associations between dementia and poverty were investigated using multivariate regression model. Findings: Of the 478 adults included, 89 (52.7%) had mild, and 25 (14.8%) had moderate to severe dementia. More women than men had mild (52.7% vs 33.3%) and moderate-to-severe dementia (14.8% vs 5.8%). Approximately 33.9% adults with mild and 51.2% adults with moderate-to-severe dementia were found to be deprived in four or more dimensions compared to 21.8% without dementia. The difference in four dimensions of multidimensional poverty between adults with mild and moderate-to-severe dementia and adults without dementia was respectively 59.5% and 152.88%. Education, employment, health, and living conditions were the main contributors to the adjusted poverty head count ratio. Multidimensional poverty in four or five dimensions was strongly associated with dementia among older adults particularly over 70 years old (odds ratio [OR], 17.38; 95% CI, 2.22-135.63), with greater odds for older women overall (OR, 2.69; 95% CI, 1.76-4.11). Interpretation: Our findings suggest that early improvement in social determinants of health through targeted structural policies may lower dementia risk later in life. Specifically, better access to free, quality education, healthcare, and basic living standard together with employment opportunities could reduce risk of dementia. Funding: The present study was funded by a grant from the Alzheimer Association (AARG-NTF-21-851241).

A practitioner's guide to geospatial analysis in a neuroimaging context.

Introduction: Health disparities arise from biological-environmental interactions. Neuroimaging cohorts are reaching sufficiently large sample sizes such that analyses could evaluate how the environment affects the brain. We present a practical guide for applying geospatial methods to a neuroimaging cohort. Methods: We estimated brain age gap (BAG) from structural magnetic resonance imaging (MRI) from 239 city-dwelling participants in St. Louis, Missouri. We compared these participants to population-level estimates from the American Community Survey (ACS). We used geospatial analysis to identify neighborhoods associated with patterns of altered brain structure. We also evaluated the relationship between Area Deprivation Index (ADI) and BAG. Results: We identify areas in St. Louis, Missouri that were significantly associated with higher BAG from a spatially representative cohort. We provide replication code. Conclusion: We observe a relationship between neighborhoods and brain health, which suggests that neighborhood-based interventions could be appropriate. We encourage other studies to geocode participant information to evaluate biological-environmental interaction.

Everyday Driving and Plasma Biomarkers in Alzheimer's Disease: Leveraging Artificial Intelligence to Expand Our Diagnostic Toolkit.

BACKGROUND: Driving behavior as a digital marker and recent developments in blood-based biomarkers show promise as a widespread solution for the early identification of Alzheimer's disease (AD). OBJECTIVE: This study used artificial intelligence methods to evaluate the association between naturalistic driving behavior and blood-based biomarkers of AD. METHODS: We employed an artificial neural network (ANN) to examine the relationship between everyday driving behavior and plasma biomarker of AD. The primary outcome was plasma Aß42/Aß40, where Aß42/Aß40 < 0.1013 was used to define amyloid positivity. Two ANN models were trained and tested for predicting the outcome. The first model architecture only includes driving variables as input, whereas the second architecture includes the combination of age, APOE ɛ4 status, and driving variables. RESULTS: All 142 participants (mean [SD] age 73.9 [5.2] years; 76 [53.5%] men; 80 participants [56.3% ] with amyloid positivity based on plasma Aß42/Aß40) were cognitively normal. The six driving features, included in the ANN models, were the number of trips during rush hour, the median and standard deviation of jerk, the number of hard braking incidents and night trips, and the standard deviation of speed. The F1 score of the model with driving variables alone was 0.75 [0.023] for predicting plasma Aß42/Aß40. Incorporating age and APOE ɛ4 carrier status improved the diagnostic performance of the model to 0.80 [>0.051]. CONCLUSION: Blood-based AD biomarkers offer a novel opportunity to establish the efficacy of naturalistic driving as an accessible digital marker for AD pathology in driving research.

Cortical atrophy and leukoaraiosis, imaging markers of cerebrovascular small vessel disease, are associated with driving behavior changes among cognitively normal older adults.

BACKGROUND: Cerebral small vessel disease (CSVD) as measured by cortical atrophy and white matter hyperintensities [leukoaraiosis], captured via magnetic resonance imaging (MRI) are increasing in prevalence due to the growth of the aging population and an increase in cardiovascular risk factors in the population. CSVD impacts cognitive function and mobility, but it is unclear if it affects complex, functional activities like driving. METHODS: In a cohort of 163 cognitively normal, community-dwelling older adults (age ≥ 65), we compared naturalistic driving behavior with mild/moderate leukoaraiosis, cortical atrophy, or their combined rating in a clinical composite termed, aging-related changes to those without any, over a two-and-a-half-year period. RESULTS: Older drivers with mild or moderate cortical atrophy and aging-related changes (composite) experienced a greater decrease in the number of monthly trips which was due to a decrease in the number of trips made within a one-to-five-mile diameter from their residence. Older drivers with CSVD experience a larger reduction in daily driving behaviors than drivers without CSVD, which may serve as an early neurobehavioral marker for functional decline. CONCLUSIONS: As CSVD markers, leukoaraiosis and cortical atrophy are standard MRI metrics that are widely available and can be used for screening individuals at higher risk for driving safety risk and decline in community mobility.