Insights on Uncovering the Gut-Brain Interaction and Cognitive Function in Alzheimer Disease

Chaoran Ma, MD, PhD

Research shows that about 16% of the global population faces challenges with constipation, with higher rates observed in older adults because of factors associated with aging such as inadequate fiber intake, sedentary lifestyles, and the use of certain medications which may lead to constipation.¹ According to a recent press release, chronic constipation has been linked to potential long-term health consequences, including inflammation, hormonal imbalances, and feelings of anxiety and depression.²

In recent research presented at the 2023 Alzheimer’s Association International Conference, held July 16-20, findings showed that less frequent bowel movements were associated with poorer cognitive function.³ Led by Chaoran Ma, MD, PhD, 3 prospective cohort studies were collected to assess the data on all participants' bowel movement frequency and their self-assessments of cognitive function.

Ma, assistant professor at University of Massachusetts Amherst, sat down with NeurologyLive® to discuss her insights on the research. She talked about the key findings of the study regarding the relationship between bowel movements and cognitive function. She also spoke about the relationship between constipation and cognitive decline in older individuals, and how clinicians can help their patients. Additionally, Ma briefly shared her thoughts on the next steps needed to gain a better understanding of the specific microbes involved and their role.

NeurologyLive: What were the key findings of the study regarding the relationship between bowel movements and cognitive function?

Chaoran Ma, MD, PhD: This study builds upon three prospective cohort studies of more than 110,000 men and women with comprehensive data collection, including the Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-up Study. In addition, this study includes a mechanistic investigation into the participants’ gut microbiome. Our study provides first-of-its-kind evidence of abnormal intestinal function being linked to cognitive decline. Specifically, we found that less frequent bowel movements were associated with poorer cognitive function. Compared to those with bowel movements once daily, constipated participants (bowel movements every 3+ days) had significantly worse cognition, equivalent to 3.0 years more of cognitive aging.

We also found a slightly increased risk of cognitive decline in those who had bowel movements more than twice a day. Moreover, our microbiome study found that individuals with specific microbial profiles in the gut, i.e., more bacteria that can cause inflammation and fewer bacteria responsible for digesting dietary fibers, had less frequent bowel movements and worse cognitive function. Our findings support considering constipation as a risk factor for cognitive decline. In addition, unhealthy microbial profiles in the gut may explain the association between abnormal intestinal function and cognitive decline.

Considering the relationship between constipation and cognitive decline in older individuals, how can clinicians help their patients?

Clinicians may want to watch for constipation in older individuals even if they are cognitively healthy because constipation may predict a higher risk of cognitive decline in the future. In addition, clinical advice and interventions for preventing constipation and improving gut health, such as adopting healthy diets enriched with high-fiber foods, such as fruits, vegetables, and whole grains, will bring cognitive health benefits.

What additional research is needed to gain a better understanding of the specific microbes involved and their role in this association?

We found that bowel movement frequency was tightly linked to the gut microbiome, and perturbations in the gut microbiome were associated with worse cognitive function. However, our study was not designed to test the causal relationship between bowel movements, the gut microbiome, and cognitive health, so we cannot firmly draw conclusions regarding the precise causal sequence underlying this association. Also, further studies are needed to identify the microbes involved, and their function.

What do you think should be done in the future to establish this definitive link between cognitive decline and gastrointestinal health?

We should watch for symptoms of abnormal intestinal function, especially constipation, in older individuals as these symptoms may hint at a higher risk of cognitive decline in the future.

Transcript edited for clarity. Click here for more coverage of AAIC 2023.

REFERENCES
1. Salari N, Ghasemianrad M, Ammari-Allahyari M, Rasoulpoor S, Shohaimi S, Mohammadi M. Global prevalence of constipation in older adults: a systematic review and meta-analysis. Wien Klin Wochenschr. 2023;10.1007/s00508-023-02156-w. doi:10.1007/s00508-023-02156-w
2. Constipation Associated with Cognitive Aging and Decline. News release. Alzheimer’s Association. Published July 19, 2023. Accessed July 19, 2023. https://www.prnewswire.com/news-releases/constipation-associated-with-cognitive-aging-and-decline-301880032.html
3. Ma C, Mei Z, Mehta RS, et al. Bowel movement frequency, the gut microbiome, and cognitive function in women and men. Presented at: 2022 Alzheimer’s Association International Conference; July 16 to July 20; Amsterdam, the Netherlands.