Cingulate white matter mediates the effects of fecal Ruminococcus on neuropsychiatric symptoms in patients with amyloid-positive amnestic mild cognitive impairment.

BACKGROUND: Microbiota-gut-brain axis interacts with one another to regulate brain functions. However, whether the impacts of gut dysbiosis on limbic white matter (WM) tracts contribute to the neuropsychiatric symptoms (NPS) in patients with amyloid-positive amnestic mild cognitive impairment (aMCI+), have not been explored yet. This study aimed to investigate the mediation effects of limbic WM integrity on the association between gut microbiota and NPS in patients with aMCI+. METHODS: Twenty patients with aMCI + and 20 healthy controls (HCs) were enrolled. All subjects underwent neuropsychological assessments and their microbial compositions were characterized using 16S rRNA Miseq sequencing technique. Amyloid deposition inspected by positron emission tomography imaging and limbic WM tracts (i.e., fornix, cingulum, and uncinate fasciculus) detected by diffusion tensor imaging were additionally measured in patients with aMCI+. We employed a regression-based mediation analysis using Hayes's PROCESS macro in this study. RESULTS: The relative abundance of genera Ruminococcus and Lactococcus was significantly decreased in patients with aMCI + versus HCs. The relative abundance of Ruminococcus was negatively correlated with affective symptom cluster in the aMCI + group. Notably, this association was mediated by WM integrity of the left cingulate gyrus. CONCLUSIONS: Our findings suggest Ruminococcus as a potential target for the management of affective impairments in patients with aMCI+.

Subjective cognitive decline exhibits alterations of resting-state phase-amplitude coupling in precuneus.

OBJECTIVE: Subjective cognitive decline (SCD) is associated with increased risks for progressing to Alzheimer's disease (AD). This study aimed to investigate phase-amplitude coupling (PAC) in individuals with SCD and healthy controls (HCs) in the baseline year and determined the predictability of cognitive changes in the clinical follow-up. METHODS: Resting-state magnetoencephalographic signals in 29 HCs and 23 SCD subjects were recorded in the baseline year. The parahippocampal gyrus, posterior cingulate cortex and precuneus were selected as regions of interest (ROIs). Based on the grand-averaged comodulograms, delta-beta, delta-gamma and theta-gamma PAC values were extracted from each ROI. RESULTS: Compared with the HCs, the SCD group showed decreased theta-gamma PAC in the precuneus. Theta-gamma PAC of the left precuneus was associated with SCD severity and performance of immediate recall in the baseline year. The SCD group was followed for 3 years and divided into SCD-Stable and SCD-Decline groups based on scores of Mini-Mental State Examination. No significant differences in PAC of the baseline year were found between SCD-Stable and SCD-Decline groups. CONCLUSIONS: The SCD group demonstrated reduced theta-gamma PAC in the precuneus. SIGNIFICANCE: Subjective perception of cognitive decline is reflected by objective alterations of brain function.

Gut microbiota in patients with Alzheimer's disease spectrum: a systematic review and meta-analysis.

CONTEXT: Gut dysbiosis has been proposed as one of pathologies in patients with Alzheimer's disease (AD) spectrum. Despite such enthusiasm, the relevant results remain substantially controversial. OBJECTIVE: A systematic review and meta-analysis were performed to investigate the differences of gut microbiota (GM) between patients with AD spectrum (including mild cognitive impairment [MCI] and AD) and healthy controls (HC). DATA SOURCES: PubMed, MEDLINE, Scopus, and Cochrane Library from January 2000 to August 2021. Eligibility criteria for study selection: Observational trials and pre-intervention data of intervention trials that investigated the abundance of GM in patients with AD spectrum and HC. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently identified articles, extracted data, and evaluated the risk of bias. The effect sizes were performed by a random-effect, inverse-variance weighted model. The effects of different countries and of clinical stages on GM abundance were also examined. RESULTS: 11 studies consisting of 378 HC and 427 patients with AD spectrum were included in the meta-analysis. Patients with AD, but not MCI, showed significantly reduced GM diversity as compared to HC. We also found more abundance of Proteobacteria, Bifidobacterium and Phascolarctobacterium, but less abundance of Firmicutes, Clostridiaceae, Lachnospiraceae and Rikenellaceae in patients with AD spectrum as compared with HC. The profiles of abundance of Alistipes and Bacteroides in HC and AD spectrum were differentially affected by countries. Finally, when considering clinical stage as a moderator, the comparisons of abundance in Clostridiaceae and Phascolarctobacterium showed large effect sizes, with gradient changes from MCI to AD stage. LIMITATIONS: The inclusion of studies originating only from China and the U.S. was a possible limitation. CONCLUSIONS: Patients with AD spectrum demonstrated altered GM abundance, which was differentially mediated by countries and clinical stages.