Participant completion of longitudinal assessments in an online cognitive aging registry: The role of medical conditions.

INTRODUCTION: This study aimed to understand whether older adults' longitudinal completion of assessments in an online Alzheimer's disease and related dementias (ADRD)-related registry is influenced by self-reported medical conditions. METHODS: Brain Health Registry (BHR) is an online cognitive aging and ADRD-related research registry that includes longitudinal health and cognitive assessments. Using logistic regressions, we examined associations between longitudinal registry completion outcomes and self-reported (1) number of medical conditions and (2) eight defined medical condition groups (cardiovascular, metabolic, immune system, ADRD, current psychiatric, substance use/abuse, acquired, other specified conditions) in adults aged 55+ (N = 23,888). Longitudinal registry completion outcomes were assessed by the completion of the BHR initial questionnaire (first questionnaire participants see at each visit) at least twice and completion of a cognitive assessment (Cogstate Brief Battery) at least twice. Models included ethnocultural identity, education, age, and subjective memory concern as covariates. RESULTS: We found that the likelihood of longitudinally completing the initial questionnaire was negatively associated with reporting a diagnosis of ADRD and current psychiatric conditions but was positively associated with reporting substance use/abuse and acquired medical conditions. The likelihood of longitudinally completing the cognitive assessment task was negatively associated with number of reported medical conditions, as well as with reporting cardiovascular conditions, ADRD, and current psychiatric conditions. Previously identified associations between ethnocultural identity and longitudinal assessment completion in BHR remained after accounting for the presence of medical conditions. DISCUSSION: This post hoc analysis provides novel, initial evidence that older adults' completion of longitudinal assessments in an online registry is associated with the number and types of participant-reported medical conditions. Our findings can inform future efforts to make online studies with longitudinal health and cognitive assessments more usable for older adults with medical conditions. The results need to be interpreted with caution due to selection biases, and the under-inclusion of minoritized communities.

Brain Health Registry Study Partner Portal: Novel infrastructure for digital, dyadic data collection.

BACKGROUND: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression. METHODS: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated. RESULTS: A total of 10,494 BHR participants (mean age = 66.9 ± 12.16 standard deviations, 67.4% female) have enrolled study partners (mean age = 64.3 ± 14.3 standard deviations, 49.3% female), including 8987 dyads with a participant 55 years of age or older. Older and more educated study partners were more likely to complete tasks and return for follow-up. Twenty-five percent to 27% of older adult participants had self and study partner-report ECog scores indicating a possible cognitive impairment. DISCUSSION: The BHR Study Partner Portal is a unique digital tool for capturing dyadic data, with high impact applications in the clinical neuroscience and AD fields. Highlights The Brain Health Registry (BHR) Study Partner Portal is a novel, digital platform of >10,000 dyads. Collection of dyadic online subjective cognitive and functional data is feasible. The portal has good usability as evidenced by positive study partner feedback. The portal is a potential scalable strategy for cognitive impairment screening in older adults.

Evaluation of the Electronic Clinical Dementia Rating for Dementia Screening.

Importance: The Clinical Dementia Rating (CDR) is a well-validated instrument widely used to detect and stage dementia due to Alzheimer disease. The digital Electronic Clinical Dementia Rating (eCDR) can be remotely self-administered and automatically scored, with potential to facilitate efficient dementia screening and staging. Objective: To evaluate the association of the eCDR with the CDR and other in-clinic assessments for screening older adults for cognitive impairment. Design, Setting, and Participants: This multisite, cross-sectional study used baseline data from a longitudinal, observational study from 2020 to 2023, including up to 3 years of follow-up. Participants were enrolled from 3 Alzheimer Disease Research Centers and the Brain Health Registry. Participants (aged ≥55 years, with a study partner, and no acute or unstable major medical conditions) were recruited during in-clinic visits or by automated emails. Exposures: Participants completed the Uniform Data Set Version 3 (UDS; including the CDR) in supervised clinical research settings, and then completed the eCDR remotely, online and unsupervised, using their own device. Main Outcomes and Measures: The primary outcomes were eCDR scores (item; categorical box and global; continuous box and global), CDR scores (item; categorical box and global), and UDS assessment scores. Associations were evaluated using linear and logistic regressions. Results: A total of 3565 participants were contacted, and 288 were enrolled. Among 173 participants with item-level data (mean [SD] age, 70.84 [7.65] years; 76 women [43.9%]), eCDR to CDR concordance was 90% or higher for 33 items (63%) and 70% to 89% for 13 items (25%). Box (domain) level concordance ranged from 80% (memory) to 99% (personal care). The global score concordance rate was 81%. κ statistics were fair to moderate. Among 206 participants with box and global scores (mean [SD] age, 71.34 [7.68] years; 95 women [46.1%]), eCDR continuous global score was associated with CDR global (categorical) score with an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.70-0.87). Correlations between eCDR and in-clinic UDS assessments were similar to those between CDR sum of box scores and the same in-clinic assessments. Conclusions and Relevance: These findings suggest that the eCDR is valid and has potential use for screening and assessment of older adults for cognitive and functional decline related to Alzheimer disease. Instrument optimization and validation in diverse cohorts in remote settings are crucial for evaluating scalability and eCDR utility in clinical research, trials, and health care settings.

Brain health registry updates: An online longitudinal neuroscience platform.

INTRODUCTION: Remote, internet-based methods for recruitment, screening, and longitudinally assessing older adults have the potential to facilitate Alzheimer's disease (AD) clinical trials and observational studies. METHODS: The Brain Health Registry (BHR) is an online registry that includes longitudinal assessments including self- and study partner-report questionnaires and neuropsychological tests. New initiatives aim to increase inclusion and engagement of commonly underincluded communities using digital, community-engaged research strategies. New features include multilingual support and biofluid collection capabilities. RESULTS: BHR includes > 100,000 participants. BHR has made over 259,000 referrals resulting in 25,997 participants enrolled in 30 aging and AD studies. In addition, 28,278 participants are coenrolled in BHR and other studies with data linkage among studies. Data have been shared with 28 investigators. Recent efforts have facilitated the enrollment and engagement of underincluded ethnocultural communities. DISCUSSION: The major advantages of the BHR approach are scalability and accessibility. Challenges include compliance, retention, cohort diversity, and generalizability. HIGHLIGHTS: Brain Health Registry (BHR) is an online, longitudinal platform of > 100,000 members. BHR made > 259,000 referrals, which enrolled 25,997 participants in 32 studies. New efforts increased enrollment and engagement of underincluded communities in BHR. The major advantages of the BHR approach are scalability and accessibility. BHR provides a unique adjunct for clinical neuroscience research.

Association of Major Depressive Disorder with remotely administered measures of cognition and subjective report of cognitive difficulties across the adult age spectrum.

BACKGROUND: Major depressive disorder (MDD) has increasing prevalence with age. Both objective measures of cognitive dysfunction and subjective report of cognitive difficulties related to MDD are often thought to worsen with increasing age. However, few studies have directly evaluated these characteristics across the adult lifespan. METHODS: Participants included 23,594 adults completing objective and subjective measures of cognition on an online research registry. Linear regression including interactions of age group with depression was used to evaluate the association of self-reported MDD with measures of cognition in three age groups: 21-40 years; 41-60 years; 61+ years. RESULTS: MDD (n = 2127) demonstrated poorer objective cognitive performance and greater subjective ratings of cognitive difficulties across all domains assessed compared to non-depressed individuals (ND; n = 21,467). Significant interactions of age group and MDD status with objective and subjective measures of cognition were observed for both middle age and older adults when compared to young adults but few significant differences between middle-aged and older adults were evident. LIMITATIONS: This study relied on self-report of MDD diagnosis, utilized remotely administered and unsupervised measures of cognition, and the sample was not diverse. CONCLUSIONS: The magnitude of association between MDD and cognitive correlates appears to plateau in middle age. Our results suggest that increased rates of dementia are not due to greater cognitive consequence of MDD in older adults and that age effects, and not greater effects of depression, may lead to increased diagnosis of MDD based on subjective report of cognitive symptoms.

Digital culturally tailored marketing for enrolling Latino participants in a web-based registry: Baseline metrics from the Brain Health Registry.

INTRODUCTION: This culturally tailored enrollment effort aims to determine the feasibility of enrolling 5000 older Latino adults from California into the Brain Health Registries (BHR) over 2.25 years. METHODS: This paper describes (1) the development and deployment of culturally tailored BHR websites and digital ads, in collaboration with a Latino community science partnership board and a marketing company; (2) an interim feasibility analysis of the enrollment efforts and numbers, and participant characteristics (primary aim); as well as (3) an exploration of module completion and a preliminary efficacy evaluation of the culturally tailored digital efforts compared to BHR's standard non-culturally tailored efforts (secondary aim). RESULTS: In 12.5 months, 3603 older Latino adults were enrolled (71% of the total California Latino BHR initiative enrollment goal). Completion of all BHR modules was low (6%). DISCUSSION: Targeted ad placement, culturally tailored enrollment messaging, and culturally tailored BHR websites increased enrollment of Latino participants in BHR, but did not translate to increased module completion. HIGHLIGHTS: Culturally tailored social marketing and website improvements were implemented. The efforts enrolled 5662 Latino individuals in 12.5 months. The number of Latino Brain Health Registry (BHR) participants increased by 122.7%. We failed to adequately enroll female Latinos and Latinos with lower education. Future work will evaluate effects of a newly released Spanish-language BHR website.

Remote blood collection from older adults in the Brain Health Registry for plasma biomarker and genetic analysis.

INTRODUCTION: Use of online registries to efficiently identify older adults with cognitive decline and Alzheimer's disease (AD) is an approach with growing evidence for feasibility and validity. Linked biomarker and registry data can facilitate AD clinical research. METHODS: We collected blood for plasma biomarker and genetic analysis from older adult Brain Health Registry (BHR) participants, evaluated feasibility, and estimated associations between demographic variables and study participation. RESULTS: Of 7150 participants invited to the study, 864 (12%) enrolled and 629 (73%) completed remote blood draws. Participants reported high study acceptability. Those from underrepresented ethnocultural and educational groups were less likely to participate. DISCUSSION: This study demonstrates the challenges of remote blood collection from a large representative sample of older adults. Remote blood collection from > 600 participants within a short timeframe demonstrates the feasibility of our approach, which can be expanded for efficient collection of plasma AD biomarker and genetic data.

Brain health registry GenePool study: A novel approach to online genetics research.

INTRODUCTION: Remote data collection, including the establishment of online registries, is a novel approach to efficiently identify risk for cognitive decline and Alzheimer's disease (AD) in older adults, with growing evidence for feasibility and validity. Addition of genetic data to online registries has the potential to facilitate identification of older adults at risk and to advance the understanding of genetic contributions to AD. METHODS: 573 older adult participants with longitudinal online Brain Health Registry (BHR) data underwent apolipoprotein E (APOE) genotyping using remotely collected saliva samples and a novel, automated Biofluid Collection Management Portal. We evaluated acceptability of genetic sample collection and estimated associations between (1) sociodemographic variables and willingness to participate in genetics research and (2) APOE results and online cognitive and functional assessments. We also assessed acceptance of hypothetical genetics research participation by surveying a larger sample of 25,888 BHR participants. RESULTS: 51% of invited participants enrolled in the BHR genetics study, BHR-GenePool Study (BHR-GPS); 27% of participants had at least one APOE ε4 allele. Older participants and those with higher educational attainment were more likely to participate. In the remotely administered Cogstate Brief Battery, APOE ε4/ε4 homozygotes (HM) had worse online learning scores, and greater decline in processing speed and attention, compared to ε3/ε4 heterozygotes (HT) and ε4 non-carriers (NC). DISCUSSION: APOE genotyping of more than 500 older adults enrolled in BHR supports the feasibility and validity of a novel, remote biofluids collection approach from a large cohort of older adults, with data linkage to longitudinal online cognitive data. This approach can be expanded for efficient collection of genetic data and other information from biofluids in the future.

Predicting amyloid status using self-report information from an online research and recruitment registry: The Brain Health Registry.

INTRODUCTION: This study aimed to predict brain amyloid beta (Aß) status in older adults using collected information from an online registry focused on cognitive aging. METHODS: Aß positron emission tomography (PET) was obtained from multiple in-clinic studies. Using logistic regression, we predicted Aß using self-report variables collected in the Brain Health Registry in 634 participants, as well as a subsample (N = 533) identified as either cognitively unimpaired (CU) or mild cognitive impairment (MCI). Cross-validated area under the curve (cAUC) evaluated the predictive performance. RESULTS: The best prediction model included age, sex, education, subjective memory concern, family history of Alzheimer's disease, Geriatric Depression Scale Short-Form, self-reported Everyday Cognition, and self-reported cognitive impairment. The cross-validated AUCs ranged from 0.62 to 0.66. This online model could help reduce between 15.2% and 23.7% of unnecessary Aß PET scans in CU and MCI populations. DISUCSSION: The findings suggest that a novel, online approach could aid in Aß prediction.

Effects of sex, race, ethnicity, and education on online aging research participation.

INTRODUCTION: This study aimed to identify the relationship of sociodemographic variables with older adults participation in an online registry for recruitment and longitudinal assessment in cognitive aging. METHODS: Using Brain Health Registry (BHR) data, associations between sociodemographic variables (sex, race, ethnicity, education) and registry participation outcomes (task completion, willingness to participate in future studies, referral/enrollment in other studies) were examined in adults aged 55+ (N = 35,919) using logistic regression. All models included sex, race, ethnicity, education, age, and subjective memory concern. RESULTS: Non-white race, being Latino, and lower educational attainment were associated with decreased task completion and enrollment in additional studies. Results for sex were mixed. DISCUSSION: The findings provide novel information about engagement in online aging-related registries, and highlight a need to develop improved engagement strategies targeting underrepresented sociodemographic groups. Increasing registry diversity will allow researchers to refer more representative populations to Alzheimer's and related dementias prevention and treatment trials.

Online study partner-reported cognitive decline in the Brain Health Registry.

INTRODUCTION: Methods for efficiently identifying cognitive decline and Alzheimer's disease (AD) are a critical unmet need. The goal of this work was to validate novel online study partner (SP)-reported outcomes to identify cognitive decline in older adults. METHODS: In older adults enrolled in the Brain Health Registry, we analyzed associations between SP-reported cognitive decline, measured by the Everyday Cognition Scale, and either (1) participant cognition, assessed by Cogstate Brief Battery or (2) participant-reported diagnosis of mild cognitive impairment or AD. RESULTS: We found strong associations between SP-reported Everyday Cognition Scale and both Cogstate scores and participant diagnosis. The associations were cognitive domain specific, dependant on participant diagnosis, and were stronger in spouse dyads and those who knew each other longer. DISCUSSION: Collecting SP-reported data online from a large cohort is feasible. Results support the construct validity of our approach, which has the potential to facilitate clinical AD and aging research.

The Brain Health Registry: An internet-based platform for recruitment, assessment, and longitudinal monitoring of participants for neuroscience studies.

INTRODUCTION: Recruitment, assessment, and longitudinal monitoring of participants for neuroscience studies and clinical trials limit the development of new treatments. Widespread Internet use allows data capture from participants in an unsupervised setting. The Brain Health Registry, a website and online registry, collects data from participants and their study partners. METHODS: The Brain Health Registry obtains self and study partner report questionnaires and neuropsychological data, including the Cogstate Brief Battery, Lumos Labs Neurocognitive Performance Test, and MemTrax Memory Test. Participants provide informed consent before participation. RESULTS: Baseline and longitudinal data were obtained from nearly 57,000 and 28,000 participants, respectively. Over 18,800 participants were referred to, and nearly 1800 were enrolled in, clinical Alzheimer's disease and aging studies, including five observational studies and seven intervention trials. DISCUSSION: Online assessments of participants and study partners provide useful information at relatively low cost for neuroscience studies and clinical trials and may ultimately be used in routine clinical practice.