Association of Cancer History with Alzheimer’s Disease Dementia and Neuropathology

Article type: Research Article

Authors: Yarchoan, Mark^a | James, Bryan D.^b | Shah, Raj C.^b | Arvanitakis, Zoe^b | Wilson, Robert S.^b | Schneider, Julie^b | Bennett, David A.^b | Arnold, Steven E.^{c; *}

Affiliations: [a] The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA | [b] Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA | [c] Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

Correspondence: [*] Correspondence to: Steven E. Arnold, MD, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA. Tel.: +1 617 643 5607; Fax: +1 617 724 1480; E-mail: [email protected].

Abstract: Background: Cancer and Alzheimer’s disease (AD) are common diseases of aging and share many risk factors. Surprisingly, however, epidemiologic data from several recent independent cohort studies suggest that there may be an inverse association between these diseases. Objective: To determine the relationship between history of cancer and odds of dementia proximate to death and neuropathological indices of AD. Methods: Using data from two separate clinical-pathologic cohort studies of aging and AD, the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP), we compared odds of AD dementia proximate to death among participants with and without a history of cancer. We then examined the relation of history of cancer with measures of AD pathology at autopsy, i.e., paired helical filament tau (PHFtau) neurofibrillary tangles and amyloid-β load. Results: Participants reporting a history of cancer had significantly lower odds of AD (OR 0.70 [0.55–0.89], p = 0.0040) proximate to death as compared to participants reporting no prior history of cancer. The results remained significant after adjusting for multiple risk factors including age, sex, race, education, and presence of an APOE ɛ4 allele. At autopsy, participants with a history of cancer had significantly fewer PHFtau tangles (p < 0.001) than participants without a history of cancer, but similar levels of amyloid-β. Conclusions: Cancer survivors have reduced odds of developing AD and a lower burden of neurofibrillary tangle deposition.

Keywords: Alzheimer’s disease, amyloid-β, cancer, cohort study, dementia, malignancy, neurofibrillary tangles, PHFtau

DOI: 10.3233/JAD-160977

Journal: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 699-706, 2017