Recruitment of African American and Non-Hispanic White Older Adults for Alzheimer Disease Research Via Traditional and Social Media: a Case Study.

The increasing prevalence of Alzheimer disease (AD), higher risk among certain ethnoracial groups, and lack of effective therapies highlights the need to recruit and enroll diverse populations in prospective, observational studies and clinical trials. However, there is little known about the effectiveness of traditional media vs. social media outreach on recruitment in aging study studies. This study retrospectively examined the effectiveness and differences in using both traditional and social media materials for the recruitment of African American (AA) versus non-Hispanic white (NHW) participants for a prospective, longitudinal study examining preclinical AD and driving outcomes. Participants needed to be at least 65 years old, drive at least an average of once weekly, own a vehicle that was manufactured in 1996 or later, and agree to cognitive testing, psychometric testing, brain magnetic resonance imaging (MRI), brain amyloid positron emission tomography (PET), and cerebrospinal fluid collection via lumbar puncture. A total of 546 individuals contacted the study coordinator by phone or email. Of those individuals, 97 enrolled and 192 were not contacted secondary to filling enrollment capacity. Sixteen participants (16.5%) were AA and the remainder were NHW. Of the 354 individuals whom the coordinator contacted back, approximately 73% declined or did not return calls. Social media was more effective with recruiting NHW participants, while traditional advertisement (newspaper) was more successful in recruiting AA participants in this urban setting. Prospective studies should balance participant burden and enrollment with a targeted, multi-tiered recruitment plan and sufficient budget to reach the population of interest.

Incident cognitive impairment: longitudinal changes in molecular, structural and cognitive biomarkers.

Longer periods are needed to examine how biomarker changes occur relative to incident sporadic cognitive impairment. We evaluated molecular (CSF and imaging), structural, and cognitive biomarkers to predict incident cognitive impairment and examined longitudinal biomarker changes before and after symptomatic onset. Data from participants who were cognitively normal, underwent amyloid imaging using Pittsburgh compound B and/or CSF studies, and at least two clinical assessments were used. Stepwise Cox proportional hazards models tested associations of molecular (Pittsburgh compound B; CSF amyloid-ß42, tau, ptau181, tau/amyloid-ß42, ptau181/amyloid-ß42), structural (normalized hippocampal volume, normalized whole brain volume), and cognitive (Animal Naming, Trail Making A, Trail Making B, Selective Reminding Test - Free Recall) biomarkers with time to Clinical Dementia Rating (CDR) > 0. Cognitively normal participants (n = 664), aged 42 to 90 years (mean ± standard deviation = 71.4 ± 9.2) were followed for up to 16.9 years (mean ± standard deviation = 6.2 ± 3.5 years). Of these, 145 (21.8%) participants developed a CDR > 0. At time of incident cognitive impairment, molecular, structural, and cognitive markers were abnormal for CDR > 0 compared to CDR = 0. Linear mixed models indicated rates of change in molecular biomarkers were similar for CDR = 0 and CDR > 0, suggesting that the separation in values between CDR = 0 and CDR > 0 must have occurred prior to the observation period. Rate of decline for structural and cognitive biomarkers was faster for CDR > 0 compared to CDR = 0 (P < 0.0001). Structural and cognitive biomarkers for CDR > 0 diverged from CDR 0 at 9 and 12 years before incident cognitive impairment, respectively. Within those who developed CDR > 0, a natural separation occurred for Pittsburgh compound B values. In particular, CDR > 0 who had at least one APOE ɛ4 allele had higher, and more rapid increase in Pittsburgh compound B, while APOE ɛ2 was observed to have slower increases in Pittsburgh compound B. Of molecular biomarker-positive participants followed for at least 10 years (n = 16-23), ∼70% remained CDR = 0 over the follow-up period. In conclusion, conversion from cognitively normal to CDR > 0 is characterized by not only the magnitude of molecular biomarkers but also rate of change in cognitive and structural biomarkers. Findings support theoretical models of biomarker changes seen during transition to cognitive impairment using longitudinal data and provide a potential time for changes seen during this transition. These findings support the use of molecular biomarkers for trial inclusion and cognitive/structural biomarkers for evaluating trial outcomes. Finally, results support a potential role for APOE ɛ in modulating amyloid accumulation in CDR > 0 with APOE ɛ4 being deleterious and APOE ɛ2 protective.

Alzheimer Disease Biomarkers and Driving in Clinically Normal Older Adults: Role of Spatial Navigation Abilities.

PURPOSE: Older adults experience impaired driving performance, and modify their driving habits, including limiting amount and spatial extent of travel. Alzheimer disease (AD)-related pathology, as well as spatial navigation difficulties, may influence driving performance and driving behaviors in clinically normal older adults. We examined whether AD biomarkers [cerebrospinal fluid (CSF) concentrations of Aß42, tau, and ptau181] were associated with lower self-reported spatial navigation abilities, and whether navigation abilities mediated the relationship of AD biomarkers with driving performance and extent. METHODS: Clinically normal older adults (n=112; aged 65+) completed an on-road driving test, the Santa Barbara Sense of Direction scale (self-report measure of spatial navigation ability), and the Driving Habits Questionnaire for an estimate of driving extent (composite of driving exposure and driving space). All participants had a lumbar puncture to obtain CSF. RESULTS: CSF Aß42, but not tau or ptau181, was associated with self-reported navigation ability. Lower self-reported navigation was associated with reduced driving extent, but not driving errors. Self-reported navigation mediated the relationship between CSF Aß42 and driving extent. CONCLUSIONS: Findings suggest that cerebral amyloid deposition is associated with lower perceived ability to navigate the environment, which may lead older adults with AD pathology to limit their driving extent.

Driving cessation over a 24-year period: Dementia severity and cerebrospinal fluid biomarkers.

INTRODUCTION: With 36 million older adult U.S. drivers, safety is a critical concern, particularly among those with dementia. It is unclear at what stage of Alzheimer's disease (AD) older adults stop driving and whether preclinical AD affects driving cessation. METHODS: Time to driving cessation was examined based on Clinical Dementia Rating (CDR) and AD cerebrospinal fluid biomarkers. 1795 older adults followed up to 24 years received CDR ratings. A subset (591) had cerebrospinal fluid biomarker measurements and was followed up to 17 years. Differences in CDR and biomarker groups as predictors of time to driving cessation were analyzed using Kaplan-Meier curves and Cox proportional models. RESULTS: Higher CDR scores and more abnormal biomarker measurements predicted a shorter time to driving cessation. DISCUSSION: Higher levels of AD biomarkers, including among individuals with preclinical AD, lead to earlier driving cessation. Negative functional outcomes of preclinical AD show a nonbenign phase of the disease.

Bridging the Technological Divide: Stigmas and Challenges With Technology in Digital Brain Health Studies of Older Adults.

The COVID-19 pandemic has increased adoption of remote assessments in clinical research. However, longstanding stereotypes persist regarding older adults' technology familiarity and their willingness to participate in technology-enabled remote studies. We examined the validity of these stereotypes using a novel technology familiarity assessment (n = 342) and with a critical evaluation of participation factors from an intensive smartphone study of cognition in older adults (n = 445). The technology assessment revealed that older age was strongly associated with less technology familiarity, less frequent engagement with technology, and higher difficulty ratings. Despite this, the majority (86.5%) of older adults elected to participate in the smartphone study and showed exceptional adherence (85.7%). Furthermore, among those enrolled, neither technology familiarity, knowledge, perceived difficulty, nor gender, race, or education were associated with adherence. These results suggest that while older adults remain significantly less familiar with technology than younger generations, with thoughtful study planning that emphasizes participant support and user-centered design, they are willing and capable participants in technology-enabled studies. And once enrolled, they are remarkably adherent.

A Systematic Review Examining Associations between Cardiovascular Conditions and Driving Outcomes among Older Drivers.

There is a vast literature on stroke as a cardiovascular disease and driving outcomes, however little is known about other cardiovascular conditions and driving. The purpose of this review is to examine the literature for studies assessing the effect of non-stroke, vascular conditions on daily driving, reported crash risk and driving decline in older adult drivers as captured by naturalistic methodologies. A systematic review of Embase, Ovid and Scopus Plus examined articles on driving and vascular conditions among older adults. A search yielded 443 articles and, following two screenings, no articles remained that focused on non-stroke, vascular conditions and naturalistic driving. As a result, this review examined non-stroke, vascular conditions in nine driving studies of older adults that used road testing, driving simulators and self-report measures. These studies fell into three categories-heart failure, vascular dementia and white matter hyperintensities/leukoaraiosis. The combined findings of the studies suggest that heart failure, vascular dementia and white matter hyperintensities (WMH) negatively impact driving performance and contribute to driving cessation among older adults. Future research should examine cardiovascular risk factors like hypertension, hypercholesterolemia, myocardial infraction or atherosclerosis using naturalistic driving measurement, as well as traditional measures, in order to more fully characterize how these conditions impact older adult driving.

Depression is Associated with Tau and Not Amyloid Positron Emission Tomography in Cognitively Normal Adults.

BACKGROUND: Depression is also common with older age. Alzheimer's disease (AD) studies suggest that both cerebrospinal fluid and positron emission tomography (PET) amyloid biomarkers are associated with more depressive symptoms in cognitively normal older adults. The recent availability of tau radiotracers offers the ability to examine in vivo tauopathy. It is unclear if the tau biomarker is associated with depression diagnosis. OBJECTIVE: We examined if tau and amyloid imaging were associated with a depression diagnosis among cognitively normal adults (Clinical Dementia Rating = 0) and whether antidepressants modified this relationship. METHODS: Among 301 participants, logistic regression models evaluated whether in vivo PET tau was associated with depression, while another model tested the interaction between PET tau and antidepressant use. A second set of models substituted PET amyloid for PET tau. A diagnosis of depression (yes/no) was made during an annual clinical assessment by a clinician. Antidepressant use (yes/no) was determined by comparing medications the participants used to a list of 30 commonly used antidepressants. All models adjusted for age, sex, education, race, and apolipoprotein ɛ4. Similar models explored the association between the biomarkers and depressive symptoms. RESULTS: Participants with elevated tau were twice as likely to be depressed. Antidepressant use modified this relationship where participants with elevated tau who were taking antidepressants had greater odds of being depressed. Relatedly, elevated amyloid was not associated with depression. CONCLUSIONS: Our results demonstrate that tau, not amyloid, was associated with a depression diagnosis. Additionally, antidepressant use interacts with tau to increase the odds of depression among cognitively normal adults.

Differences in Driving Outcomes Among Cognitively Normal African American and Caucasian Older Adults.

OBJECTIVE: To examine the effect of race in driving performance and behavior prospectively among cognitively normal older adults. METHODS: Cognitively normal participants (Clinical Dementia Rating 0), ≥ 65 years of age (n = 177) were selected from prospective, longitudinal studies at the Knight Alzheimer Disease Research Center at Washington University. Self-reported driving behavior (Driving Habits Questionnaire) and driving performance (road test) were annually assessed. Daily driving behavior data were collected using the Driving Real World In-Vehicle Evaluation System (DRIVES). Baseline differences between African Americans and Caucasians were tested using t tests and general linear models. Amyloid imaging and cerebrospinal fluid Alzheimer disease (AD) biomarkers were compared across groups. Linear mixed models examined change in daily driving behavior over time. Survival analyses tested time to a marginal or fail rating on the road test. RESULTS: There were no differences between African Americans (n = 34) and Caucasians (n = 143) in age, sex, education, or vascular risk factors. Baseline self-reported driving behavior and road test performance were largely similar for both races. Longitudinal analyses using the DRIVES data aggregated monthly showed that African Americans had a greater reduction in number of trips made per month, miles driven per month, and trips with aggressive behavior compared to Caucasians. These effects remained after controlling for AD biomarkers, age, education, and sex. CONCLUSIONS: In this sample of cognitively normal older adults, African Americans had a greater reduction of daily driving behavior compared to Caucasians. Observed racial differences may reflect differences in environmental/social factors, changes in cognition, and/or physical functioning.

A Naturalistic Study of Driving Behavior in Older Adults and Preclinical Alzheimer Disease: A Pilot Study.

A clinical consequence of symptomatic Alzheimer's disease (AD) is impaired driving performance. However, decline in driving performance may begin in the preclinical stage of AD. We used a naturalistic driving methodology to examine differences in driving behavior over one year in a small sample of cognitively normal older adults with ( n = 10) and without ( n = 10) preclinical AD. As expected with a small sample size, there were no statistically significant differences between the two groups, but older adults with preclinical AD drove less often, were less likely to drive at night, and had fewer aggressive behaviors such as hard braking, speeding, and sudden acceleration. The sample size required to power a larger study to determine differences was calculated.

A 2.5-Year Longitudinal Assessment of Naturalistic Driving in Preclinical Alzheimer's Disease.

BACKGROUND: Emerging evidence shows that cognitively normal older adults with preclinical Alzheimer's disease (AD) make more errors and are more likely to receive a marginal/fail rating on a standardized road test compared to older adults without preclinical AD, but the extent to which preclinical AD impacts everyday driving behavior is unknown. OBJECTIVE: To examine self-reported and naturalistic longitudinal driving behavior among persons with and without preclinical AD. METHOD: We prospectively followed cognitively normal drivers (aged 65 + years) with (n = 10) and without preclinical AD (n = 10) for 2.5 years. Preclinical AD was assessed using amyloid positron emission tomography (PET) with Pittsburgh Compound B. The Driving Habits Questionnaire assessed self-reported driving outcomes. Naturalistic driving was captured using a commercial GPS data logger plugged into the on-board diagnostics II port of each participant's vehicle. Data were sampled every 30 seconds and all instances of speeding, hard braking, and sudden acceleration were recorded. RESULTS: Preclinical AD participants went to fewer places/unique destinations, traveled fewer days, and took fewer trips than participants without preclinical AD. The preclinical AD group reported a smaller driving space, greater dependence on other drivers, and more difficulty driving due to vision difficulties. Persons with preclinical AD had fewer trips with any aggression and showed a greater decline across the 2.5-year follow-up period in the number of days driving per month and the number of trips between 1-5 miles. CONCLUSION: Changes in driving occur even during the preclinical stage of AD.

Driving Outcomes among Older Adults: A Systematic Review on Racial and Ethnic Differences over 20 Years.

The population of older adults (aged 65 years and older) in the United States will become more racially and ethnically diverse in the next three decades. Additionally, the growth of the aging population will come with an expansion in the number of older drivers and an increased prevalence of chronic neurological conditions. A major gap in the aging literature is an almost exclusive focus on homogenous, non-Hispanic white samples of older adults. It is unclear if this extends to the driving literature. A systematic review of SCOPUS, PubMed, CINAHL Plus, and Web of Science examined articles on driving and racial/ethnic differences among older adults. Eighteen studies met inclusion criteria and their results indicate that racial and ethnic minorities face a greater risk for driving reduction, mobility restriction, and driving cessation. The majority of studies compared African Americans to non-Hispanic whites but only examined race as a covariate. Only four studies explicitly examined racial/ethnic differences. Future research in aging and driving research needs to be more inclusive and actively involve different racial/ethnic groups in study design and analysis.

Tau and Amyloid Positron Emission Tomography Imaging Predict Driving Performance Among Older Adults with and without Preclinical Alzheimer's Disease.

Abnormal levels of Alzheimer's disease (AD) biomarkers, measured by positron emission tomography imaging using amyloid-based radiotracers and cerebrospinal fluid, are associated with impaired driving performance in older adults. We examined whether preclinical AD staging, defined using amyloid imaging and tau imaging using the radiotracer T807 (AKA flortaucipir or AV-1451), was associated with receiving a marginal/fail rating on a standardized road test (n = 42). Participants at Stage 2 (positive amyloid and tau scans) of preclinical AD were more likely to receive a marginal/fail rating compared to participants at Stage 0 or 1. Stage 2 preclinical AD may manifest in worse driving performance.

Depression and Alzheimer's Disease Biomarkers Predict Driving Decline.

BACKGROUND: Symptomatic Alzheimer's disease (AD) and depression independently increase crash risk. Additionally, depression is both a risk factor for and a consequence of AD. OBJECTIVE: To examine whether a depression diagnosis, antidepressant use, and preclinical AD are associated with driving decline among cognitively normal older adults. METHODS: Cognitively normal participants, age ≥65, were enrolled. Cox proportional hazards models evaluated whether a depression diagnosis, depressive symptoms (Geriatric Depression Scale), antidepressant use, cerebrospinal fluid (amyloid-ß42 [Aß42], tau, phosphorylated tau181 [ptau181]), and amyloid imaging biomarkers (Pittsburgh Compound B and Florbetapir) were associated with time to receiving a rating of marginal/fail on a road test. Age was adjusted for in all models. RESULTS: Data were available from 131 participants with age ranging from 65.4 to 88.2 years and mean follow up of 2.4 years (SD = 1.0). A depression diagnosis was associated with a faster time to receiving a marginal/fail rating on a road test and antidepressant use (p = 0.024, HR = 2.62). Depression diagnosis and CSF and amyloid PET imaging biomarkers were associated with driving performance on the road test (p≤0.05, HR = 2.51-3.15). In the CSF ptau181 model, depression diagnosis (p = 0.031, HR = 2.51) and antidepressant use (p = 0.037, HR = 2.50) were statistically significant predictors. There were no interaction effects between depression diagnosis, antidepressant use, and biomarker groups. Depressive symptomology was not a statistically significant predictor of driving performance. CONCLUSIONS: While, as previously shown, preclinical AD alone predicts a faster time to receiving a marginal/fail rating, these results suggest that also having a diagnosis of depression accelerates the onset of driving problems in cognitively normal older adults.

Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers Predict Driving Decline: Brief Report.

We examined whether neuropsychiatric symptoms (NPS) interact with cerebrospinal fluid (CSF) biomarkers (amyloid-ß42 [Aß42], tau, phosphorylated tau181 [ptau181], tau/Aß42, and ptau181/Aß42) of Alzheimer's disease pathology to predict driving decline among cognitively-normal older adults (N = 116) aged ≥65. Cox proportional hazards models examined time to receiving a rating of marginal or fail on the driving test. Age, education, and gender were adjusted in the models. Participants with more abnormal CSF (Aß42, tau/Aß42, ptau181/Aß42) and NPS were faster to receive a marginal/fail on the road test compared to those without NPS. NPS interact with abnormal CSF biomarkers to impact driving performance among cognitively-normal older adults.

Preclinical Alzheimer's disease and longitudinal driving decline.

INTRODUCTION: Links between preclinical AD and driving difficulty onset would support the use of driving performance as an outcome in primary and secondary prevention trials among older adults (OAs). We examined whether AD biomarkers predicted the onset of driving difficulties among OAs. METHODS: 104 OAs (65+ years) with normal cognition took part in biomarker measurements, a road test, clinical and psychometric batteries and self-reported their driving habits. RESULTS: Higher values of CSF tau/Aß42 and ptau181/Aß42 ratios, but not uptake on PIB amyloid imaging (p=.12), predicted time to a rating of Marginal or Fail on the driving test using Cox proportional hazards models. Hazards ratios (95% confidence interval) were 5.75 (1.70-19.53), p=.005 for CSF tau/Aß42; 6.19 (1.75-21.88) and p=.005 for CSF ptau181/Aß42. DISCUSSION: Preclinical AD predicted time to receiving a Marginal or Fail rating on an on-road driving test. Driving performance shows promise as a functional outcome in AD prevention trials.

Creating a driving profile for older adults using GPS devices and naturalistic driving methodology.

Background/Objectives: Road tests and driving simulators are most commonly used in research studies and clinical evaluations of older drivers. Our objective was to describe the process and associated challenges in adapting an existing, commercial, off-the-shelf (COTS), in-vehicle device for naturalistic, longitudinal research to better understand daily driving behavior in older drivers. Design: The Azuga G2 Tracking Device TM was installed in each participant's vehicle, and we collected data over 5 months (speed, latitude/longitude) every 30-seconds when the vehicle was driven.  Setting: The Knight Alzheimer's Disease Research Center at Washington University School of Medicine. Participants: Five individuals enrolled in a larger, longitudinal study assessing preclinical Alzheimer disease and driving performance.  Participants were aged 65+ years and had normal cognition. Measurements:  Spatial components included Primary Location(s), Driving Areas, Mean Centers and Unique Destinations.  Temporal components included number of trips taken during different times of the day.  Behavioral components included number of hard braking, speeding and sudden acceleration events. Methods:  Individual 30-second observations, each comprising one breadcrumb, and trip-level data were collected and analyzed in R and ArcGIS.  Results: Primary locations were confirmed to be 100% accurate when compared to known addresses.  Based on the locations of the breadcrumbs, we were able to successfully identify frequently visited locations and general travel patterns.  Based on the reported time from the breadcrumbs, we could assess number of trips driven in daylight vs. night.  Data on additional events while driving allowed us to compute the number of adverse driving alerts over the course of the 5-month period. Conclusions: Compared to cameras and highly instrumented vehicle in other naturalistic studies, the compact COTS device was quickly installed and transmitted high volumes of data. Driving Profiles for older adults can be created and compared month-to-month or year-to-year, allowing researchers to identify changes in driving patterns that are unavailable in controlled conditions.

Association of Functional Impairments and Co-Morbid Conditions with Driving Performance among Cognitively Normal Older Adults.

OBJECTIVES: To examine the relationship between key functional impairments, co-morbid conditions and driving performance in a sample of cognitively normal older adults. DESIGN: Prospective observational study. SETTING: The Knight Alzheimer's Disease Research Center, Washington University at St. Louis. PARTICIPANTS: Individuals with normal cognition, 64.9 to 88.2 years old (N = 129), with a valid driver's license, who were currently driving at least once per week, and who had participated in longitudinal studies at the Knight Alzheimer's Disease Research Center. MEASUREMENTS: Static visual acuity, contrast sensitivity, physical frailty measures, motor skills, total medical conditions, and the modified Washington University Road Test. RESULTS: When controlling for age, race, gender, APOE, and education the total number of medical conditions was unassociated with both road test scores (pass vs. marginal + fail) and the total driver error count. There were marginal associations of our measure of physical frailty (p = 0.06) and contrast sensitivity score (p = 0.06) with total driving error count. CONCLUSION: Future research that focuses on older adults and driving should consider adopting measures of physical frailty and contrast sensitivity, especially in samples that may have a propensity for disease impacting visual and/or physical function (e.g. osteoarthritis, Parkinson's, eye disorders, advanced age >80 years, etc.).

Development and interval testing of a naturalistic driving methodology to evaluate driving behavior in clinical research.

Background: The number of older adults in the United States will double by 2056. Additionally, the number of licensed drivers will increase along with extended driving-life expectancy. Motor vehicle crashes are a leading cause of injury and death in older adults. Alzheimer's disease (AD) also negatively impacts driving ability and increases crash risk. Conventional methods to evaluate driving ability are limited in predicting decline among older adults. Innovations in GPS hardware and software can monitor driving behavior in the actual environments people drive in. Commercial off-the-shelf (COTS) devices are affordable, easy to install and capture large volumes of data in real-time. However, adapting these methodologies for research can be challenging. This study sought to adapt a COTS device and determine an interval that produced accurate data on the actual route driven for use in future studies involving older adults with and without AD.  Methods: Three subjects drove a single course in different vehicles at different intervals (30, 60 and 120 seconds), at different times of day, morning (9:00-11:59AM), afternoon (2:00-5:00PM) and night (7:00-10pm). The nine datasets were examined to determine the optimal collection interval. Results: Compared to the 120-second and 60-second intervals, the 30-second interval was optimal in capturing the actual route driven along with the lowest number of incorrect paths and affordability weighing considerations for data storage and curation. Discussion: Use of COTS devices offers minimal installation efforts, unobtrusive monitoring and discreet data extraction.  However, these devices require strict protocols and controlled testing for adoption into research paradigms.  After reliability and validity testing, these devices may provide valuable insight into daily driving behaviors and intraindividual change over time for populations of older adults with and without AD.  Data can be aggregated over time to look at changes or adverse events and ascertain if decline in performance is occurring.