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P1‐004: GUT DYSBIOSIS INITIATES METABOLIC DISTURBANCE, COGNITIVE DECLINE, AND MICROGLIAL HYPERACTIVITY IN HIGH‐FAT‐DIET‐INDUCED OBESE RATS
Author(s) -
Saiyasit Napatsorn,
Chunchai Titikorn,
Prus Dillon,
Suparan Kanokphong,
Pratchayasakul Wasana,
Sripetchwandee Jirapas,
Chattipakorn Nipon,
Chattipakorn Siriporn C.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.065
Subject(s) - endocrinology , cognitive decline , hippocampal formation , medicine , morris water navigation task , gut flora , dyslipidemia , dysbiosis , insulin resistance , hippocampus , microglia , biology , insulin , inflammation , obesity , immunology , dementia , disease
Background: The Apolipoprotein (ApoE) ε4 allele is the strongest known genetic risk factor for Alzheimer’s disease (AD; Lind et al., 2006). Olfactory impairment is one of the earliest signs of AD (Albers et al., 2014). To our knowledge, no previous study has examined the interaction of sex and ApoE ε4 status in differential olfactory memory processing utilizing neuroimaging data within elderly individuals. The present study investigates olfactory memory task performance while ApoE ε4 carriers and non-carriers completed a functional magnetic resonance imaging (fMRI) and structural scan.Methods: Participants were (N1⁄4 39) non-demented older adults, ranging in age from 64 to 88 years. Individuals with at least one ε4 allele were classified as ε4 carriers (n 1⁄4 18). Individuals without the ε4 allele (n 1⁄4 21) were classified as non-carriers. Prior to the fMRI scan, participants were presented with 16 odors from the California Odor Learning Test (COLT; Murphy et al., 1997). During the scan, participants were presented with labels of odors and asked to decide if the label was presented prior to the scan (target) or not (foil). Results: ε4 carriers demonstrated significantly (p < .05) greater atrophy in the left cingulate cortex when compared to ε4 non-carriers. Regression analyses revealed that for ε4 carriers average rates for correctly identifying a target (hit) were positively associated with cingulate cortex thickness. While committing hits, male ApoE ε4 carriers demonstrated significantly (p < .015) greater activation in the right parahippocampal gyrus, right hippocampus, and precuneus when compared to female e4 carriers. Conclusions: Results suggest different structural and functional changes in relation to ε4 status that may influence olfactory memory. Greater functional activation within male e4 carriers in relation to female ε4 carriers suggests that males require a greater cognitive expenditure in areas crucial to episodic memory retrieval; greater cognitive expenditure suggests less neuronal efficiency (Stoub et al., 2006; Bonn ı et al., 2015). Future studies may consider utilizing this paradigm within a longitudinal study to examine neuronal changes over time. Acknowledgements: Lori Haase, MiRan Wang, and Erin Green. Supported by NIH grant number: AG004085-26.