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AAIC 2023 | Gut microbiome composition and cognitive function in middle-aged adults

Jazmyn A Muhammad, BS, Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at The University of Texas Health Science Center at San Antonio, San Antonio, TX, shares her work looking at the association between cognitive scores and gut microbiome structure in middle-aged adults. Participants of the Framingham Heart Study with no history of stroke or dementia were studied. Gut microbiome composition was quantified using 16S rRNA sequencing and global cognitive scores were calculated based on neuropsychological assessments of executive function, processing speed, language, and memory. The results from over 1000 participants demonstrated an association between cognition and the abundance of several genera, including Pseudobutyrivibrio and Alistipes, which were found to be more abundant in the poor cognition group (first quintile of cognitive scores). An increased abundance of E. bolteae was also noted in the poor cognition group. Additionally, the analysis showed an increase in trimethylamine producing bacteria to be associated with poorer cognition. These species have been previously linked to cerebrovascular disease, diabetes, and obesity through the production of detrimental metabolites. These data demonstrate the intimate relationship between cognitive function and gut homeostasis and evidence the need for further investigation into potential driving or mediating factors. This interview took place at the Alzheimer’s Association International Conference® (AAIC) 2023 in Amsterdam, Netherlands.

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Transcript (edited for clarity)

Our aim was to assess the association between cognition, measured with general cognitive scores, and the gut microbiome structure. We use data from the third-generation cohort from the Framingham Heart Study and filtered for middle aged adults with no history of stroke or dementia and who had completed a cognitive assessment as well as provided a stool sample. Some additional demographic characteristics were obtained and adjusted for such as BMI, age, sex, education and the time interval between the cognitive assessment and the stool collection...

Our aim was to assess the association between cognition, measured with general cognitive scores, and the gut microbiome structure. We use data from the third-generation cohort from the Framingham Heart Study and filtered for middle aged adults with no history of stroke or dementia and who had completed a cognitive assessment as well as provided a stool sample. Some additional demographic characteristics were obtained and adjusted for such as BMI, age, sex, education and the time interval between the cognitive assessment and the stool collection. The stool sample was sequenced and the microbiome composition was estimated using 16S RNA methods and then finally, we use multivariable association and differential abundance analysis to estimate the association between the bacteria abundance and the general cognitive scores.

Our general cognitive scores were computed based on neuropsychological assessment of four cognitive domains. Those included executive functioning, processing speed, language, and memory and the composite score was used to estimate how cognitive dysfunction relates to the gut microbiome structure. In addition, participants were stratified into two groups. One was the poor cognition and those were participants in the first quintile of scores and then from normal cognition was from the second to the fifth quintile scores

So participants in the poor group had significantly increased abundance of a species boltea and through both multivariable association and differential abundance analysis, it suggested that poor cognition was associated with an increased abundance of trimethylamine producing species and this has been linked to several detrimental metabolites leading to cardiovascular disease, type two diabetes obesity, suggesting that this could be a potential target for age related diseases. And this species was only seen in the poorer cognitive participants, leading us to believe that those who tested well didn’t have this species. So it could be something either in their diet, their genetics, maybe medications that had led them to have an abundance of this bacteria.

While these results are promising, there’s still much to be analyzed. Like I was saying, like with the diet, medication, genetics and of course, cardiovascular disease to look for some driving or mediating factors with the association of microbiome and cognition. So at this moment, we don’t know what bacteria or maybe any other factors that could be driving or mediating, but that is something that we’re going to be looking into in our next analysis, as well as more research needed for diverse populations. We did use the cohort from the Framingham Heart Study, which may not be reflective of the US population.

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