Development and validation of an episodic memory measure in the Mobile Toolbox (MTB): Arranging Pictures.

INTRODUCTION: Arranging Pictures is a new episodic memory test based on the NIH Toolbox (NIHTB) Picture Sequence Memory measure and optimized for self-administration on a personal smartphone within the Mobile Toolbox (MTB). We describe evidence from three distinct validation studies. METHOD: In Study 1, 92 participants self-administered Arranging Pictures on study-provided smartphones in the lab and were administered external measures of similar and dissimilar constructs by trained examiners to assess validity under controlled circumstances. In Study 2, 1,021 participants completed the external measures in the lab and self-administered Arranging Pictures remotely on their personal smartphones to assess validity in real-world contexts. In Study 3, 141 participants self-administered Arranging Pictures remotely twice with a two-week delay on personal iOS smartphones to assess test-retest reliability and practice effects. RESULTS: Internal consistency was good across samples (ρxx = .80 to .85, p < .001). Test-retest reliability was marginal (ICC = .49, p < .001) and there were significant practice effects after a two-week delay (ΔM = 3.21 (95% CI [2.56, 3.88]). As expected, correlations with convergent measures were significant and moderate to large in magnitude (ρ = .44 to .76, p < .001), while correlations with discriminant measures were small (ρ = .23 to .27, p < .05) or nonsignificant. Scores demonstrated significant negative correlations with age (ρ = -.32 to -.21, p < .001). Mean performance was slightly higher in the iOS compared to the Android group (MiOS = 18.80, NiOS = 635; MAndroid = 17.11, NAndroid = 386; t(757.73) = 4.17, p < .001), but device type did not significantly influence the psychometric properties of the measure. Indicators of potential cheating were mixed; average scores were significantly higher in the remote samples (F(2, 850) = 11.415, p < .001), but there were not significantly more perfect scores. CONCLUSION: The MTB Arranging Pictures measure demonstrated evidence of reliability and validity when self-administered on personal device. Future research should examine the potential for cheating in remote settings and the properties of the measure in clinical samples.

Remote olfactory assessment using the NIH Toolbox Odor Identification test and the brain health registry.

BACKGROUND: Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. To realistically enable population-level measurements of olfaction, validated olfaction tests must be capable of being administered outside the research laboratory and clinical setting. AIM: The purpose of this study was to determine the feasibility of remotely testing olfactory performance using a test that was developed with funding from the National Institutes of Health as part of a ready-to-use, non-proprietary set of measurements useful for epidemiologic studies (NIH Toolbox Odor ID Test). MATERIALS AND METHODS: Eligible participants older than 39 years and active (within 6 months) in the Brain Health Registry (BHR), an online cognitive assessment platform which connects participants with researchers, were recruited for this study. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses. Data obtained from subjects who performed the test at home was compared to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting and validated against the Smell Identification Test. The age-range and composition of the population ensured we had the ability to observe both age-related decline and gender-related deficits in olfactory ability, as shown in the experimental setting. RESULTS: We observed that age-associated olfactory decline and gender-associated performance was comparable to performance on the administered test. Self-administration of this test showed the age-related loss in olfactory acuity, F(4, 1156)=14.564, p<.0001 as well as higher accuracy for women compared to men after controlling for participants' age, F(1, 1160) = 22.953, p <.0001. The effect size calculated as Hedge's g, was 0.41. CONCLUSION: These results indicate that the NIH Toolbox Odor ID Test is an appropriate instrument for self-administered assessment of olfactory performance. The ability to self-administer an inexpensive olfactory test increases its utility for inclusion in longitudinal epidemiological studies and when in-person testing is not feasible.

Development and Validation of a Vocabulary Measure in the Mobile Toolbox.

OBJECTIVE: We describe the development of a new computer adaptive vocabulary test, Mobile Toolbox (MTB) Word Meaning, and validity evidence from 3 studies. METHOD: Word Meaning was designed to be a multiple-choice synonym test optimized for self-administration on a personal smartphone. The items were first calibrated online in a sample of 7,525 participants to create the computer-adaptive test algorithm for the Word Meaning measure within the MTB app. In Study 1, 92 participants self-administered Word Meaning on study-provided smartphones in the lab and were administered external measures by trained examiners. In Study 2, 1,021 participants completed the external measures in the lab and Word Meaning was self-administered remotely on their personal smartphones. In Study 3, 141 participants self-administered Word Meaning remotely twice with a 2-week delay on personal iPhones. RESULTS: The final bank included 1363 items. Internal consistency was adequate to good across samples (ρxx = 0.78 to 0.81, p < .001). Test-retest reliability was good (ICC = 0.65, p < .001), and the mean theta score was not significantly different upon the second administration. Correlations were moderate to large with measures of similar constructs (ρ = 0.67-0.75, p < .001) and non-significant with measures of dissimilar constructs. Scores demonstrated small to moderate correlations with age (ρ = 0.35 to 0.45, p < .001) and education (ρ = 0.26, p < .001). CONCLUSION: The MTB Word Meaning measure demonstrated evidence of reliability and validity in three samples. Further validation studies in clinical samples are necessary.

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.

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.

Reliability and Validity of a Home-Based Self-Administered Computerized Test of Learning and Memory Using Speech Recognition.

INTRODUCTION: The objective of this study is to evaluate the reliability and validity of the ReVeReTM word list recall test (RWLRT), which uses speech recognition, when administered remotely and unsupervised. METHODS: Prospective cohort study. Participants included 249 cognitively intact community dwelling older adults. Measures included clinician administered neuropsychological assessments at baseline and unsupervised remotely administered tests of cognition from six time-points over six months. RESULTS: The RWLRT showed acceptable validity. Reliability coefficients varied across time points, with poor reliability between times 1 and 2 and fair-to-good reliability across the remaining five testing sessions. Practice effects were observed with repeated administration as expected. DISCUSSION: Unsupervised computerized tests of cognition, particularly word list learning and memory tests that use speech recognition, have significant potential for large scale early detection and long-term tracking of cognitive decline due to AD.

rPOP: Robust PET-only processing of community acquired heterogeneous amyloid-PET data.

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (18F-florbetapir/FBP, 18F-florbetaben/FBB or 18F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with the image as it is. We validate rPOP with n = 740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the Imaging Dementia-Evidence for Amyloid Scanning - Brain Health Registry sub-study (IDEAS-BHR) and n = 1,518 scans from the Alzheimer's Disease Neuroimaging Initiative (n = 1,249 FBP, n = 269 FBB), including heterogeneous acquisition and reconstruction protocols. After running rPOP, a standard quantification to extract Standardized Uptake Value ratios and the respective Centiloids conversion was performed. rPOP-based amyloid status (using an independent pathology-based threshold of ≥24.4 Centiloid units) was compared with either local visual reads (IDEAS-BHR, n = 663 with complete valid data and reads available) or with amyloid status derived from an MRI-based PET processing pipeline (ADNI, thresholds of >20/>18 Centiloids for FBP/FBB). Finally, within the ADNI dataset, we tested the linear associations between rPOP- and MRI-based Centiloid values. rPOP achieved accurate warping for N = 2,233/2,258 (98.9%) in the first pass. Of the N = 25 warping failures, 24 were rescued with manual reorientation and origin reset prior to warping. We observed high concordance between rPOP-based amyloid status and both visual reads (IDEAS-BHR, Cohen's k = 0.72 [0.7-0.74], ∼86% concordance) or MRI-pipeline based amyloid status (ADNI, k = 0.88 [0.87-0.89], ∼94% concordance). rPOP- and MRI-pipeline based Centiloids were strongly linearly related (R2:0.95, p<0.001), with this association being significantly modulated by estimated PET resolution (ß= -0.016, p<0.001). rPOP provides reliable MRI-free amyloid-PET warping and quantification, leveraging widely available software and only requiring an attenuation-corrected amyloid-PET image as input. The rPOP pipeline enables the comparison and merging of heterogeneous datasets and is publicly available at https://github.com/leoiacca/rPOP.

Hoarding disorder is associated with self-reported cardiovascular / metabolic dysfunction, chronic pain, and sleep apnea.

Hoarding behaviors are positively associated with medical morbidity, however, current prevalence estimates and types of medical conditions associated with hoarding vary. This analysis aims to quantify the medical morbidity of hoarding disorder (HD). Cross-sectional data were collected online using the Brain Health Registry (BHR). Among 20,745 participants who completed the Hoarding and Clutter and Medical History thematic modules, 1348 had HD (6.5%), 1268 had subclinical HD (6.1%), and 18,829 did not meet hoarding criteria (87.4%). Individuals with HD were more likely to report a lifetime history of cardiovascular/metabolic conditions: diabetes (HD adjusted odds ratio (AOR):1.51, 95% confidence interval (CI):[1.20, 1.91]; subclinical HD AOR:1.24, 95% CI:[0.95, 1.61]), and hypercholesterolemia (HD AOR:1.24, 95% CI:[1.06, 1.46]; subclinical HD AOR:1.11, 95% CI:[0.94, 1.31]). Those with HD and subclinical HD were also more to report chronic pain (HD AOR: 1.69, 95% CI:[1.44, 1.98]; subclinical HD AOR: 1.44, 95% CI:[1.22, 1.69]), and sleep apnea (HD AOR: 1.58, 95% CI:[1.31, 1.89]; subclinical HD AOR:1.30, 95% CI:[1.07, 1.58]) than non-HD participants. For most conditions, likelihood of diagnosis did not differ between HD and subclinical HD. Structural equation modeling revealed that more severe hoarding symptomatology was independently associated with increased cardiovascular/metabolic vulnerability. The assessment and management of medical complications in individuals with HD is a fundamental component in improving quality of life, longevity, and overall physical health outcomes.

Internet-based hoarding assessment: The reliability and predictive validity of the internet-based Hoarding Rating Scale, Self-Report.

The Hoarding Rating Scale, Self Report (HRS-SR) is a 5-item assessment developed to ascertain the presence and severity of hoarding symptoms. This study aimed to evaluate the validity of an online adaptation of the HRS-SR in a remote, unsupervised internet sample of 23,214 members of the Brain Health Registry (BHR), an online research registry that evaluates and longitudinally monitors cognition, medical and psychiatric health status. Convergent validity was assessed among a sub-sample of 1,183 participants who completed additional, remote measures of self-reported hoarding behaviors. Structured clinical interviews conducted in-clinic and via video conferencing tools were conducted among 230 BHR participants; ROC curves were plotted to assess the diagnostic performance of the internet-based HRS-SR using best estimate hoarding disorder (HD) diagnoses as the gold standard. The area under the curve indicated near-perfect model accuracy, and was confirmed with 10-fold cross validation. Sensitivity and specificity for distinguishing clinically relevant hoarding were optimized using an HRS-SR total score cut-off of 5. Longitudinal analyses indicated stability of HRS-SR scores over time. Findings indicate that the internet-based HRS-SR is a useful and valid assessment of hoarding symptoms, though additional research using samples with more diverse hoarding behavior is needed to validate optimal cut-off values.

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.

Validation of online functional measures in cognitively impaired older adults.

INTRODUCTION: Assessment of functional status is associated with risk of cognitive decline and diagnosis of dementia, and can be assessed by participants and study partners (SPs). METHODS: In 770 older adults enrolled in the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study and the online Brain Health Registry (BHR), we estimated associations between online assessments and clinical variables related to Alzheimer's disease (AD) risk. RESULTS: Worse online learning scores and SP-reported functional decline were associated with higher probability of AD dementia diagnosis and poor in-clinic cognitive assessment, and with higher odds of amyloid beta (Aß) positivity when combined with participants' report of less decline. SP report of functional decline conferred predictive value independent of online cognitive assessments. Participants underreported decline compared to SPs. DISCUSSION: The results support the validity of online assessments and their greater utilization in healthcare and research settings. Online SP-reported functional decline is an indicator of dementia and AD risk.

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.