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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.

Background: Increasing evidence connects the gut microbiome to Parkinson’s disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. Objective: We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. Methods: In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). Results: PD patients’ gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis. PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. Two genera were associated with motor function. Conclusion: PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression.

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.