In a recent press release by the Alzheimer's Association International Conference (AAIC), researchers report the worsening of cognition among chronically constipated individuals.
Study: Constipation Associated with Cognitive Aging and Decline. Image Credit: Perfect Wave / Shutterstock.com
Alzheimer’s disease (AD) risk is linked to the gut microbiome, with dysbiosis contributing to neurological disorders like AD. However, the relationship between brain and gut health, gut dysbiosis, and cognitive changes is understudied.
Fecal microbiota transplantation (FMt) may reduce amyloid plaques in AD models. The frequency of bowel movements may also impact dementia risk.
Constipation prevalence is high among the older population due to aging-associated factors such as fiber-deficient diets, physical inactivity, and the usage of constipating medications to treat medical disorders. Chronic constipation, which is described as the occurrence of bowel movements every three days or more, is linked to health consequences such as hormonal imbalance, inflammation, depression, and anxiety.
In the current study, researchers analyze data from three studies, including over 110,000 individuals in the Health Professionals Follow-up Study (HPFS), as well as Nurses’ Health Study (NHS)-I and II, to determine the association between digestive health and cognition. They also assessed the contribution of gut microbes to the associations based on data from 515 HPFS and NHS-II participants.
Data were obtained on the frequency of bowel movements among participants between 2012 and 2013 and subjectively assessed cognitive functions between 2014 and 2017. Cognition was objectively measured using neuropsychological batteries from 2014 to 2018 among 12,696 individuals. The gut microbiota was profiled using shotgun metagenomic analysis.
Constipation is related to poorer cognition and increased cognitive aging
A lower frequency of bowel movements was related to worse cognitive functions. As compared to individuals with one bowel movement every day, constipated individuals showed significantly poorer cognitive performance, which was equivalent to three more years of cognitive age. Bowel movement once every three days or more was related to 73% greater odds of self-reported cognitive decay.
Butyrate-producing bacteria and dietary fiber digestion were depleted among individuals with lower frequencies of bowel motion and poorer cognitive functions. Increased counts of dysbiosis-associated pro-inflammatory bacterial species were related to bowel movements two or more times daily and poorer cognitive functions.
These findings underscore the need for health professionals to discuss gastrointestinal health, particularly constipation, with geriatric patients.
A new relationship between Alzheimer’s disease and gut microbes
Researchers assessed the relationship between Aβ-amyloid buildup in AD and the gut microbiome using stool samples and cognitive neuropathological assessments from 140 cognitively unimpaired middle-aged individuals with a mean age of 56 years, 54% of whom were female within the Framingham Heart Study (FHS).
Positron emission tomography (PET) was performed to evaluate Aβ and tau protein deposition in the inferior and rhinal cortical regions of the brain. Gut microbes were quantified using 16S ribosomal ribonucleic acid (rRNA) sequencing. Differential abundance and multivariate association analyses were performed, adjusting for confounders such as age, sex, and body mass index (BMI).
Increased tau and Aβ deposits were observed in the brains of individuals with a lower abundance of neuroprotective butyrate-producing bacteria such as Ruminococcus and Butyricicoccus. Aβ-PET OR values for Ruminococcus and Butyricicoccus were 0.9 and 0.8, respectively, with corresponding values for tau deposition within the rhinal cortices of 0.8 and 0.9, respectively, and for tau deposition within the inferotemporal cortices of 0.8.
Contrastingly, elevated counts of Cytophaga and Alistipes, with odds ratio (OR) values of 1.8 and 1.2 for tau protein deposition within the rhinal cortices, respectively, were observed. The findings highlighted the link between the gut and AD.
The link between the gut microbiome and cognition
Gut health and the brain are interlinked through the gut-brain axis. Researchers assessed the relationship between global cognitive scores (GCS) and the gut microbiota among 1,014 middle-aged FHS participants with a mean age of 52 years, 55% of whom were female and did not have a history of stroke or dementia. The stool samples of these patients were obtained, in addition to their cognitive test scores.
GCS was based on neuropsychological evaluations of cognitive domains such as executive function, processing speed, language, and memory. Individuals with poor cognition exhibited decreased Clostridium and Ruminococcus abundance, as well as increased Alistipes and Pseudobutyrivibrio abundance, with OR values of 0.7, 0.9, 1.1, and 1.1, respectively. These findings indicate that the gut microbiome could impact the cognitive capacity of middle-aged and older adults.
These findings begin to reveal more specific connections between our gut and our brain. For example, we believe that the reduction of certain identified bacteria may increase gut permeability and the transport of toxic metabolites in the brain, thus increasing amyloid-beta and tau deposition.”