How Alzheimer’s Disease Is Linked With Hygiene

Do you worry about things being too dirty? If you do, let me add to your anxieties and suggest that you should also worry about things being too clean, at least if you want to enjoy optimal health in the modern world.

A recent study provides evidence that rates of Alzheimer’s disease rise in lockstep with increased levels of hygiene and reduced rates of infection. These results come from an investigation of differences in age-standardized disability-adjusted life-year, or “DALY,” rates attributable to Alzheimer’s disease across 192 countries [1]. Super-hygienic countries with low rates of infection, such as Switzerland, have rates of Alzheimer’s disease that are 12% higher than rates observed in the world’s least hygienic (and most infection-plagued) nations. More strikingly, approximately one-third of the difference between nations in rates of Alzheimer’s disease was accounted for by differences in hygiene and infection.

If you don’t share my obsession with the impact of the microbial world on mental health, these results might seem to have tumbled out of the blue devoid of any reasonable explanation. But if you follow this literature, these findings are exactly what one would have predicted in advance, given what we know about the relationship between hygiene and the rates of many other immune-related illnesses in the modern world.

Multiple lines of evidence suggest that as we’ve cleaned up our world in an attempt to separate ourselves from killer microbes, we have inadvertently also separated ourselves from many other micro-organisms that conferred profound health benefits [2].

This idea is popularly known as the “Hygiene Hypothesis”; however, we prefer the alternate term “Old Friends Hypothesis” to highlight the fact that it is not hygiene per se that is the problem, but the fact that hygiene, and multiple other aspects of the modern world, have separated us from microbes and parasites with which we co-evolved and which have powerful anti-inflammatory and immune system modulating effects, especially when one is exposed to them in infancy.

While we think of the immune system as primarily involved in fighting infection, on a deeper level it is really a communication pathway between us and the world of the very small [3]. Just as important as warding off dangerous intruders is an ability to recognize and tolerate microbes that either pose no threat or actually contribute to health (think of the bacteria that produce vitamin K in our guts).

At the heart of the “Old Friends Hypothesis” is the notion that because many micro-organisms and parasites were always present across human evolution and had to be tolerated, they became “teachers of tolerance.” Said differently, over time the human immune system outsourced some of its tolerance training to the Old Friends, an arrangement that worked quite well until the Old Friends were banished from our lives over the last century [4].

Lacking the “brake” on the immune system provided by the Old Friends, individuals with any genetic risk for heightened inflammation were suddenly left unprotected and vulnerable to whichever flavor of inflammatory or autoimmune condition their genetic inheritance made them most likely to contract. In the absence of Old Friend-induced immunomodulation, some people develop allergies or asthma, while others develop rheumatoid arthritis, type I diabetes, or multiple sclerosis. Still others have primary vulnerabilities in the central nervous system, developing autism after birth, schizophrenia or depression early in life and, yes, Alzheimer’s in old age.

Like the legion of autoimmune conditions that have exploded in prevalence over the last 100 years, autism, schizophrenia, depression, and most definitively Alzheimer’s disease are all associated with increased inflammation and reductions in key immunoregulatory immune cells (e.g., regulatory T and dendritic cells) whose activities are enhanced by contact with Old Friends organisms.

More than just a fantastical notion, these ideas have very real preventive health and clinical implications.

We don’t want to return to the “good old days” when approximately 50% of all children were dead from infectious causes by age 15, but neither do we want to “throw the baby out with the bathwater” and deny our children exposure to other organisms that might be essential for optimal immune, and hence brain, development. How to strike this balance is an area of just-emerging but active research

Perhaps the most impressive demonstration of the therapeutic relevance of the Old Friends comes from ongoing studies of Mycobacterium vaccae (M. vaccae), once common in mud and untreated water, but now banished from our lives. M vaccae is showing great promise in the treatment of various cancers (see www.immodulon.com for details). In the largest study conducted to date, M vaccae also showed positive effects on mood, energy, and cognitive functioning, making it a fascinating potential candidate for future exploration as an addition to our psychiatric armamentarium [5].

As a personal postscript, I slept through the infectious disease lectures in my first year of medical school, or drowned out the instructor by passing notes to a woman I had a crush on. I knew I wanted to be a psychiatrist, so I assumed that all the mumbo-jumbo about bacteria and other bugs was totally irrelevant to my life ambitions. Never have I been more wrong.

(Editor’s Note: The findings relating hygiene and Alzheimer’s disease can be read in their entirety at https://emph.oxfordjournals.org/content/2013/1/173.full.pdf+html. Except for the book “The New Mind-Body Science of Depression,” which is due to be published late in 2014, all other references in this article can be downloaded for free from PubMed. For a slightly dated but still excellent review of the relationship between modern health/sanitation practices, microbes, and human health, see the book “Good Germs, Bad Germs” by Jessica Snyder Sachs.)

1. Fox, M, Knapp, LA, Andrews, PW, Fincher, CL., Hygiene and the world distribution of Alzheimer's disease. Evolution, Medicine and Public Health, 2013. Epub.

2. Rook, G.A., Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol. 2012. 42(1):5-15.

3. Maletic,V,  Raison CL, The New Mind-Body Science of Depression. 2014, New York: W.W. Norton.

4. Raison, CL, Lowry CA,  Rook GA, Inflammation, sanitation, and consternation: loss of contact with coevolved, tolerogenic microorganisms and the pathophysiology and treatment of major depression. Arch Gen Psychiatry. 2010. 67(12):1211-1224.

5. O'Brien, ME, et al. SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results. Ann Oncol. 2004. 15(6):906-914.

Charles L. Raison, MD, is an associate professor in the Department of Psychiatry, College of Medicine and the Barry and Janet Lang Associate Professor of Integrative Mental Health in the Norton School of Family and Consumer Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ. He is also the behavioral health expert for CNN.com, and he is a Psych Congress Steering Committee member.

The views expressed on this blog are solely those of the blog post author and do not necessarily reflect the views of Psych Congress Network or other Psych Congress Network authors.