Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk

Objective: To explore the association of nonmelanoma skin cancer (NMSC) and Alzheimer disease (AD) in the Einstein Aging Study, an epidemiologic study of aging in New York City. Methods: Community-residing volunteers aged 70 years or older were assessed annually, followed by multidisciplinary diagnostic consensus. Cancer status and type was obtained by self-report. Cox proportional hazards models were used to test associations between NMSC and subsequent risk of developing a neurocognitive disorder. To deduce a biologically specific association between AD and NMSC, we considered 3 nested outcomes groups: only AD (probable or possible AD as the sole diagnosis), any AD (probable AD or possible AD, as well as mixed AD/vascular dementia), and all-cause dementia. Results: We followed 1,102 adults with a mean age of 79 years at enrollment. Prevalent NMSC was associated with reduced risk of only AD (hazard ratio = 0.21;95% confidence interval = 0.051-0.87; p = 0.031) among subjects after adjustment for demographics, hypertension, diabetes, and coronary heart disease. APOE s4 genotypes were available in 769 individuals. The association was similar in magnitude, but nonsignificant, when the number of APOE s4 alleles was included in the model. No significant association was found between NMSC and subsequent development of any AD or all-cause dementia. Conclusions: This population-based longitudinal study shows that individuals older than 70 years with NMSC have a significantly reduced risk of developing AD compared with individuals without NMSC. We deduce Alzheimer-specific neuroprotection, because the effect is attenuated or eliminated when considering less-specific diagnoses such as AD with another diagnosis (any AD) or all-cause dementia.