Constipation and Dementia: When the First Brain Warns the Second

A sixty-eight-year-old woman came to me about words. Nouns, mostly, and the names of people she had known for decades. Her screening score was called borderline and she was told to return in a year. Nobody asked about the constipation she had handled with two laxatives since her early fifties.

That sequence, bowel first and memory second, is why constipation and dementia belong in the same conversation. I am Dr. Gurpreet Singh Padda, MD, MBA, MHP, and the video above covers the brain-barrier scans and the bacteria debate from The Angry Gut, the book I wrote with Ami Michelle Grimes. This page goes further: absolute risk, the confounders inside stool research, and what a pain practice does with a patient like her.

The gut is the first brain. The skull holds the second. The vagus nerve tethers them, and they share a blood supply. When one of them has been inflamed for sixteen years, the other is not a bystander.

A clean colonoscopy is not a clean bill of health

Her colonoscopy in her late fifties found nothing. A scope answers one narrow question, whether cancer is growing on the colon wall. It cannot tell you how fast the tube moves or what crosses its lining. A normal scope became a closed file.

It is the billing map. Her bowel belongs to one specialist and her memory belongs to another, and no code pays either one to ask about the other organ. The patient is left carrying the connection alone. People in chronic pain know this structure well: a spine doctor, a psychiatrist and a gastroenterologist who never compare notes, which is exactly why a scan that does not match the pain so often ends a workup instead of starting one.

What large cohorts show about constipation and dementia

The biggest dataset followed 462,327 middle-aged and older adults. Constipation came before a combined outcome of stroke, dementia and Parkinson’s disease at an adjusted hazard ratio of 1.35. Broken out, the added risk was 20% for stroke, 50% for dementia and 56% for Parkinson’s (Yun et al., 2025).

Now the absolute numbers. Among people with constipation, 1415 of 20,263 went on to one of those events, or 7.0%. Among people without it, 18,848 of 442,064 did, or 4.3%. That is a 2.7-point gap over years of follow-up. Real, and modest. How the constipation was recorded changed the answer too: self-report carried a hazard ratio of 1.31, while a coded diagnosis carried 1.44.

Stroke on that list is the tell. A bowel signal that forecasts three different brain diseases is not pointing at one plaque or one misfolded protein. It is pointing at a shared terrain, loaded with metabolic and inflammatory stress, that can fail in more than one direction. The link was also strongest within the first two years, which is the pattern reverse causation leaves behind. Both readings can be true together.

Parkinson’s disease gives the sharpest version. In a national database that compared it with healthy controls and with Alzheimer’s and cerebrovascular disease, four gut syndromes came first specifically: a stomach that empties too slowly, trouble swallowing, irritable bowel without diarrhea, and constipation (Konings et al., 2023). Diarrhea and fecal incontinence did not separate it. The slow bowel carried the signal, not the loose one.

Why a stool test from a slow bowel misleads

Here is what most microbiome marketing leaves out. Stool consistency moves every headline marker a microbiome kit reports: richness, the balance between the major bacterial groups, and the enterotype label (Vandeputte et al., 2016). In 53 healthy women, faster transit favored fast-growing species. Bacteria that survive a fast tube divide quickly. Slow the tube and a different crowd wins.

People with Parkinson’s are constipated at an odds ratio of 6.1 against controls in the largest metagenomic study, and they used laxatives at an odds ratio of 3.8 (Wallen et al., 2022). That team ran the test that settles the question in people who did not have the disease. Constipation produced the same drop in spore-forming gene groups in healthy controls, and a stronger one: a fold change of 0.58 in controls against 0.76 in the Parkinson’s group.

So a species list from a constipated person is largely a readout of the constipation. The census is not the activity. It counts who lives in the tube, not what they did today. A bowel habit is treatable, and it deserves a plan before anyone sells you a species list as a diagnosis.

Gut inflammation, endotoxin and the second brain

What actually travels from the first brain to the second? On the best-controlled evidence it is traffic, not a colony: bacterial products and immune signals crossing a barrier that no longer closes well.

Twelve healthy young men given intravenous endotoxin developed fever and a surge in interleukin-6, cortisol and norepinephrine, yet memory, attention and executive function did not budge (Grigoleit et al., 2010). A single dose in healthy volunteers is not sixteen years of an inflamed bowel in a woman in her late sixties. Trial entry rules screen that patient out.

The chronic picture looks different. Among 217 older adults, roughly a third of them cognitively impaired, the impaired group carried interleukin-6 three times higher and stool calprotectin, the protein white cells leave behind in an inflamed bowel, four times higher. The strongest single correlation with cognition was stool calprotectin, at r = -0.573 (Arikawa et al., 2025). The study is cross-sectional and was not adjusted for age, but it points at the bowel rather than the blood.

For someone living with chronic pain, this lands twice. The metabolic inflammation that loosens a barrier is the same engine that keeps a nervous system on high alert, which is why high insulin can make you hurt and why belly fat pumps out inflammatory signals long before a memory score slips. The spinal side of that traffic is the subject of how the gut reaches the spine.

The gums, and a pill that did not hold

The mouth is the likeliest open door. Examine the gums after a dementia diagnosis and the pooled odds ratio is 2.26. Measure the gums first and follow people forward, and the hazard ratio shrinks to 1.15 (Kim & Han, 2025). The gap between those two figures is recall bias, and severe disease carried the entire association.

Then a drug was designed to block the gum bacterium’s protein-cutting enzymes and tested in 643 people with mild to moderate Alzheimer’s disease. Every arm declined by about the same amount. It missed both primary endpoints, liver enzymes rose past three times normal in 7 and 15 percent on the two doses, and the program was stopped (Alzforum, 2022). People also left the drug arms faster: 163 of 217 finished on placebo, against 129 of 214 on the high dose (Cortexyme, 2022).

A late pill in established disease is not the same as closing a door early. Severe periodontitis is still a treatable inflammatory load.

What a pain practice does with a slow gut and a slipping memory

Here is what I told her.

• The barrier problem is metabolic before it is neurological. In healthy older adults, a high body mass index and waist-hip ratio predicted a leaking brain barrier twenty years later, and that leak tracked diabetes rather than amyloid or APOE genotype (Janelidze et al., 2017). So the levers are the ones that move a waistline and a fasting insulin: what you eat, when you eat, how you sleep and whether you move.
• Ask why the bowel stopped. A laxative keeps things moving. It never asks the question. Stool calprotectin is a simple way to start asking.
• Get the gums examined with numbers. If there is severe periodontitis, treat it as the inflammatory load it is.
• Write down the years your bowel changed and your memory did.

None of this means stopping a laxative or any other medication on your own. Work every change through with your physician. Chronic pain adds its own layer to the memory question, and whether chronic pain raises dementia risk deserves the same visit. Every study behind these figures, with its limits, is in the Deep Dive for Chapter 12. The next step down the same system is what unresolved trauma does to the bowel.

Seal the first brain anyway. The metabolic case for it does not wait on the bacteria debate.

Frequently asked questions

Can constipation cause dementia?

A link is not proof of cause. In a cohort of 462,327 adults, people with constipation had 50% higher dementia risk, and the association was strongest in the first two years, which also fits a slow brain disease that shows up in the gut first. See how the vagus nerve carries signals between the gut and the brain.

Is gum disease linked to dementia?

Yes, but less strongly than headlines suggest. Studies that examine gums after diagnosis show roughly double the odds, while studies that follow people forward find a hazard ratio of 1.15, and only severe disease carries the association. Severe periodontitis is still inflammation worth treating. Read why we treat inflammatory load at its metabolic source.

Can gut inflammation cause brain fog?

Chronic gut inflammation travels with thinking problems in older adults. In 217 people, those with cognitive impairment had stool calprotectin four times higher and interleukin-6 three times higher, and stool calprotectin correlated with cognition more strongly than any blood marker. The study was cross-sectional, so it shows association, not cause. Learn how a fire in the gut shows up as anxiety and mood symptoms.

Should I get a microbiome stool test for memory problems?

Be cautious. Stool consistency drives most of what a microbiome kit reports, and constipation alone produces the same bacterial signature seen in Parkinson’s disease, even in healthy people. A species list from a slow bowel is mostly a report on the slow bowel. Stool calprotectin, which measures inflammation, is often the more useful question. Find out why the popular leaky gut test cannot see the gut wall.

What should I bring to a memory appointment if I have gut symptoms?

Bring a timeline with years, not decades: when bowel symptoms started, when memory changed, and which laxatives or other medications you use. Ask about your waist measurement and fasting insulin in the same visit, since body size and diabetes tracked a leaking brain barrier. Ask whether stool calprotectin makes sense for you. See what a computerized cognitive assessment measures.

Sources

1. Yun, Q., Wang, S., Li, B., Yang, Z., Wei, C., Yuan, J., Hu, J., Li, Y., Yang, Z., Sha, F., & Tang, J. (2025). Constipation preceding stroke, dementia and Parkinson’s disease in middle-aged and older adults: a population-based cohort study. Age and Ageing, 54(9), afaf257. https://doi.org/10.1093/ageing/afaf257
2. Konings, B., Villatoro, L., Van den Eynde, J., Barahona, G., Burns, R., McKnight, M., Hui, K., Yenokyan, G., Tack, J., & Pasricha, P. J. (2023). Gastrointestinal syndromes preceding a diagnosis of Parkinson’s disease: testing Braak’s hypothesis using a nationwide database for comparison with Alzheimer’s disease and cerebrovascular diseases. Gut, 72(11), 2103-2111. https://doi.org/10.1136/gutjnl-2023-329685
3. Wallen, Z. D., Demirkan, A., Twa, G., Cohen, G., Dean, M. N., Standaert, D. G., Sampson, T. R., & Payami, H. (2022). Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms. Nature Communications, 13(1), 6958. https://doi.org/10.1038/s41467-022-34667-x
4. Vandeputte, D., Falony, G., Vieira-Silva, S., Tito, R. Y., Joossens, M., & Raes, J. (2016). Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut, 65(1), 57-62. https://doi.org/10.1136/gutjnl-2015-309618
5. Arikawa, A. Y., Waterman, A., Mishra, S. P., Labyak, C., Williams, C., Chaudhari, D. S., Shukla, R., Kumar, V., Masternak, M., Holland, P., Golden, A., Dangiolo, M., Kociolek, J., Fraser, A., Agronin, M., Aymat, M., Yadav, H., & Jain, S. (2025). Cognitive impairment is associated with alterations in diet quality and inflammatory biomarkers in older adults: a cross-sectional analysis of data collected from the Microbiome in Aging Gut and Brain (MiaGB) Consortium cohort. The Journal of Nutrition, Advance online publication (PubMed record carries no volume/issue/pages). https://doi.org/10.1016/j.tjnut.2025.06.026
6. Grigoleit, J. S., Oberbeck, J. R., Lichte, P., Kobbe, P., Wolf, O. T., Montag, T., del Rey, A., Gizewski, E. R., Engler, H., & Schedlowski, M. (2010). Lipopolysaccharide-induced experimental immune activation does not impair memory functions in humans. Neurobiology of Learning and Memory, 94(4), 561-7. https://doi.org/10.1016/j.nlm.2010.09.011
7. Kim, D.-H., & Han, G.-S. (2025). Periodontitis as a risk factor for dementia: A systematic review and meta-analysis. The Journal of Evidence-Based Dental Practice, 25(2), 102094. https://doi.org/10.1016/j.jebdp.2025.102094
8. Cortexyme, Inc. (sponsor). ClinicalTrials.gov registry record NCT03823404. (2022). GAIN Trial: A randomized, double-blind, placebo-controlled study of COR388 in subjects with Alzheimer’s disease. https://clinicaltrials.gov/study/NCT03823404
9. Alzforum (Biomedical Research Forum, LLC). Therapeutics database entry: Atuzaginstat. (2022). Atuzaginstat (COR388) – Alzforum Therapeutics entry. https://www.alzforum.org/therapeutics/atuzaginstat
10. Janelidze, S., Hertze, J., Nägga, K., Nilsson, K., Nilsson, C., Wennström, M., van Westen, D., Blennow, K., Zetterberg, H., & Hansson, O. (2017). Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype. Neurobiology of Aging, 51, 104-112. https://doi.org/10.1016/j.neurobiolaging.2016.11.017

Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP, board certified in anesthesiology, pain medicine, interventional pain management, addiction medicine and obesity medicine. Adapted from Chapter 12 of The Angry Gut by Dr. Padda and Ami Michelle Grimes. Last reviewed September 2026.

Dr. Gurpreet Singh Padda, MD, MBA, MHP