Parkinson's Disease and the Gut Microbiome in Rural California.

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 16S 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 pathway. 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. Clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression.

Unsupervised mobile cognitive testing for use in preclinical Alzheimer's disease.

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.

Exploration of microbiota targets for major depressive disorder and mood related traits.

Growing evidence suggests the link between gut microbiota and mood regulation. The current study aimed to identify microbiota targets for major depressive disorder (MDD) and mood-related traits in Taiwanese samples, while taking into account the influence of dietary patterns. We recruited 36 MDD patients and 37 healthy controls for 16S rRNA gene sequencing. We assessed nutrient content using food frequency questionnaire, and mood related phenotypes, including depressive severity, anxiety, and perceived stress. Analysis of composition of microbiomes (ANCOM) models were performed to evaluate microbiota compositions between patients and controls, while adjusted for fat intake% and sequencing platforms. We found 23 taxa (4 phyla, 7 families and 12 genera) to be associated with depression and beta diversity was differed between groups. Phylum Actinobacteria and Firmicutes were overrepresented in MDD patients. At genus level, Bifidobacterium (7%) and Blautia (8%) had relatively high abundance among MDD patients, while Prevotella (16%) had high abundance in controls. Holdemania exhibited moderate correlation with anxiety (r = 0.65) and perceived stress level (r = 0.49) mainly in MDD patients but not controls. Pathway analyses revealed that pentose phosphate and starch and sucrose metabolism processes were important pathways for depression via microbiota functions. In conclusion, our results revealed microbiota targets for depression that are independent of fat intake. It is worthwhile to conduct further studies to replicate the current findings and to integrate with biochemistry and metabolomics data to better understand the functions of identified targets.