Hygiene and the world distribution of Alzheimer's disease: Epidemiological evidence for a relationship between microbial environment and age-adjusted disease burden

Abstract

Background and objectives: Alzheimer's disease (AD) shares certain etiological features with autoimmunity. Prevalence of autoimmunity varies between populations in accordance with variation in environmental microbial diversity. Exposure to microorganisms may improve individuals' immunoregulation in ways that protect against autoimmunity, and we suggest that this may also be the case for AD. Here, we investigate whether differences in microbial diversity can explain patterns of age-adjusted AD rates between countries.

Methodology: We use regression models to test whether pathogen prevalence, as a proxy for microbial diversity, across 192 countries can explain a significant amount of the variation in age-standardized AD disability-adjusted life-year (DALY) rates. We also review and assess the relationship between pathogen prevalence and AD rates in different world populations.

Results: Based on our analyses, it appears that hygiene is positively associated with AD risk. Countries with greater degree of sanitation and lower degree of pathogen prevalence have higher age-adjusted AD DALY rates. Countries with greater degree of urbanization and wealth exhibit higher age-adjusted AD DALY rates.

Conclusions and implications: Variation in hygiene may partly explain global patterns in AD rates. Microorganism exposure may be inversely related to AD risk. These results may help predict AD burden in developing countries where microbial diversity is rapidly diminishing. Epidemiological forecasting is important for preparing for future healthcare needs and research prioritization.

Keywords: Alzheimer’s disease; Darwinian medicine; dementia; hygiene hypothesis; inflammation; pathogen prevalence.

Figure 1.

Countries’ parasite stress negatively correlated to Alzheimer's burden Countries with higher contemporary parasite prevalence have lower age-standardized rates of Alzheimer’s in 2004. N = 190, R² = 0.373, P < 0.0000. Contemporary parasite stress [55] combines years 2002 and 2009, and the variable is transformed by adding a constant and taking square root. The Alzheimer variable is transformed by adding a constant and taking the natural log of 2004 Alzheimer age-standardized DALY [36]

Figure 2.

Countries’ historical disease prevalence negatively correlated to Alzheimer’s burden 2004 Countries with historically more infectious disease have lower age-standardized rates of Alzheimer’s in 2004. N = 148, R² = 0.358, P < 0.0000. Historical disease prevalence 9-item data compiled by Murray and Schaller for years 1944–61 [54]. Alzheimer prevalence variable is transformed by adding a constant and taking the natural log of 2004 Alzheimer age-standardized DALY [36]

Figure 3.

Countries’ urbanization 1960 positively correlated to Alzheimer's burden 2004 Countries with more of the population living in urban areas in 1960 have higher age-standardized rates of Alzheimer’s in 2004. N = 187, R² = 0.282, P < 0.0000. Urbanization data [57] are transformed by adding a constant and taking the square root. The Alzheimer prevalence variable is transformed by adding a constant and taking the natural log of 2004 Alzheimer age-standardized DALY [36]

Figure 4.

Contemporary environment may be better indicator of Alzheimer's burden than early-life environment For each year (x), the regression coefficient (y) of the correlation between year’s (x) IMR and AD burden in 2004. IMR for the various years were transformed by square root and natural log. See Supplementary Section S5. All correlations were significant besides the years 1900, 1901 and 1911. Significance: 1902–19, P < 0.05; 1920–44, P < 0.01; 1945–2002, P < 0.000