Introduction We determine whether diminished Learning Over Repeated Exposures (LORE) identifies subtle memory decrements in cognitively unimpaired (CU) older adults with Alzheimer's disease (AD) biomarker burden. Methods Ninety‐four CU participants (mean age = 77.6 ± 5.02) completed a challenging associative memory test, at home, monthly, for up to 1 year (mean = 9.97 months) on a study‐issued iPad. Learning curves for face‐name memory were computed for two versions completed monthly: same face‐name pairs (A‐A‐A) and alternate face‐name pairs (B‐C‐D). Positron emission tomography (PET) imaging characterized global amyloid (Pittsburgh Compound‐B (PiB); amyloid beta (Aβ)+/−) and regional tau burden (flortaucipir). Results Diminished LORE for same (but not alternate) face‐name pairs was associated with greater amyloid and tau burden. Aβ+/− group differences for same face‐name pairs emerged by the fourth exposure and was of medium‐to‐large magnitude (Cohen's d = 0.66; 95% confidence interval [CI] = 0.25‐1.08). Discussion Subtle decrements in learning related to AD pathological burden in CU are detectable over short time‐intervals (ie, months). Implications for prevention trial design are discussed.

Introduction Unsupervised digital cognitive testing is an appealing means to capture subtle cognitive decline in preclinical Alzheimer's disease (AD). Here, we describe development, feasibility, and validity of the Boston Remote Assessment for Neurocognitive Health (BRANCH) against in‐person cognitive testing and amyloid/tau burden. Methods BRANCH is web‐based, self‐guided, and assesses memory processes vulnerable in AD. Clinically normal participants (n = 234; aged 50–89) completed BRANCH; a subset underwent in‐person cognitive testing and positron emission tomography imaging. Mean accuracy across BRANCH tests (Categories, Face‐Name‐Occupation, Groceries, Signs) was calculated. Results BRANCH was feasible to complete on participants’ own devices (primarily smartphones). Technical difficulties and invalid/unusable data were infrequent. BRANCH psychometric properties were sound, including good retest reliability. BRANCH was correlated with in‐person cognitive testing ( r = 0.617, P < .001). Lower BRANCH score was associated with greater amyloid ( r = –0.205, P = .007) and entorhinal tau ( r = –0.178, P = .026). Discussion BRANCH reliably captures meaningful cognitive information remotely, suggesting promise as a digital cognitive marker sensitive early in the AD trajectory.

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Background Detailed longitudinal neuropsychological assessment in the Harvard Aging Brain Study (HABS) and related studies has revealed that subtle decrements in associative and semantic memory, as well as reduced practice effects for repeated items may be the earliest cognitive changes in preclinical AD. Utilizing digital, repeated, and remote assessment of these cognitive functions has the potential to increase the rapidity and ease with which these subtle changes can be detected. We previously showed that diminished practice effects on a challenging iPad‐based monthly face‐name memory paradigm was associated with neuroimaging markers of amyloid and tau in normal older adults participating in HABS. These findings inspired the development of the Boston Remote Assessment of Neurocognitive Health (BRANCH), a smartphone‐based associative and semantic memory assessment using stimuli and tasks relevant to everyday life designed for serial assessment. Method We describe the development, feasibility, and pilot data from a smartphone‐based memory assessment administered daily (over consecutive days) in normal older adults using their own devices. BRANCH includes 2 measures of paired associative learning (faces and names, groceries and prices), an associative memory test with facilitated encoding (categories), and a continuous visual recognition task (street signs). A total of 41 pilot participants (mean age=76.1; 64% female) completed 1 version of BRANCH in clinic and 4 versions remotely on their own mobile device for 4 consecutive days. Participants also completed standard paper and pencil testing and a questionnaire about their experience completing the task. Result BRANCH was feasible with a total of 80% of individuals completing all assessments in the correct order. It was acceptable to participants with 64% finding the tasks at‐least somewhat to highly engaging. Older age and general cognition (e.g., MMSE) was associated with worse performance across memory tasks. Improved performance (practice effect) was observed on daily administration of paired associative memory tasks (Figure 1.). Conclusion A theoretically and evidence‐based digital memory assessment with ecologically‐valid tasks and stimuli is feasible for older adults to complete independently on their own devices. Digital assessment over multiple timepoints has the potential to drastically improve the efficiency with which cognitive performance and subtle decline can be captured.

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BackgroundDespite progress, disparities in Alzheimer’s Disease (AD) research participation continue to be a problem. Underrepresentation of certain racial and ethnic groups can result from several factors, including narrow recruitment strategies and strict exclusion criteria, and hinders our understanding of AD. We examined racial/ethnic differences in recruitment and screen failure in the Harvard Aging Brain Study (HABS), a longitudinal observational study, to elucidate these discrepancies.MethodWe analyzed HABS screening data from September 2010 to December 2021. Eligible participants were 50‐90 years old, cognitively intact (based on CDR, Logical Memory, and MMSE scores), in stable physical health, and had a study partner who could answer questions about their daily functioning. Participants were categorized into four mutually exclusive racial/ethnic groups based on self‐report data: Hispanic/Latino, White, Black, and other (Asian, American Indian/Alaskan Native, >1 Race, or did not disclose). Screen fail reasons were divided into clinical/cognitive, MRI/PET contraindications, medical and psychiatric history, and other. Statistical analyses included chi‐square, odds ratio, and t‐tests.ResultThe racial/ethnic breakdown of the 514 screened participants was 72.0% White, 14.0% Black, 10.9% Hispanic/Latino, and 3.1% other. Black participants had lower mean years of education than White participants (p < .05; Black, Mean [SD] = 14.28 [2.76]; White, 16.00 [2.96]). A total of 18.7% of participants screen failed with 17.8% of White, 19.4% of Black, and 28.6% of Hispanic/Latino participants (p > .05). Clinical/cognitive test scores were the most common reason for screen failure across all participants (41.7%), followed by medical history (26.0%). There were differences across racial/ethnic groups; compared with White participants, Black (odds ratio (OR), 2.6, 95% CI, 1.1‐5.6; p < .05) and Hispanic/Latino (OR, 2.7; 95% CI, 1.0‐6.1; p < .05) were more likely to meet exclusion criteria for cognition.ConclusionWhile efforts have been made to broaden recruitment strategies, create a Spanish‐language cohort, and revise exclusion criteria, racial/ethnic differences in recruitment and screen failure of HABS participants persist. This reflects a continued need to identify more culturally appropriate cognitive tests, norms, and cutoffs. Discovering and analyzing disparities by race/ethnicity will inform future efforts to create inclusive cohorts, leading to more representative AD research.