Progression of Alzheimer’s Disease by Self-Reported Cancer History in the Alzheimer’s Disease Neuroimaging Initiative

Article type: Research Article

Authors: Fowler, Mackenzie E.^{a; *} | Triebel, Kristen L.^b | Cutter, Gary R.^c | Schneider, Lon S.^d | Kennedy, Richard E.^e | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Epidemiology, University of Alabama, Birmingham, Birmingham, AL, USA | [b] Division of Neuropsychology, Department of Neurology, University of Alabama, Birmingham, Birmingham, AL, USA | [c] Department of Biostatistics, University of Alabama, Birmingham, Birmingham, AL, USA | [d] University of Southern California Keck School of Medicine, Los Angeles, CA, USA | [e] Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama, Birmingham, Birmingham, AL, USA

Correspondence: [*] Correspondence to: Mackenzie E. Fowler, MPH, 933 19th Street South, CH19-218P, Birmingham, AL 35294, USA. Tel.: +1 205 975 4394; E-mail: [email protected].

Note: [1 ] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/themes/freshnews-devv2/documents/policy/ADNI_Acknowledgement_List% 205-29-18.pdf

Abstract: Background:Cross-sectional studies suggest self-reported cancer history is associated with decreased risk of Alzheimer’s disease (AD). However, little is known about how self-reported cancer affects longitudinal AD progression, the primary outcome in clinical trials and observational studies. Objective:To determine self-reported cancer history’s effect on longitudinal AD progression in an observational study. Methods:We utilized data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to evaluate progression to AD by self-reported all-cancer, breast, prostate, colorectal, or non-melanoma skin cancer history. Linear mixed effects models were used to examine baseline differences and rates of progression on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) by self-reported cancer history. Age at AD onset was examined using consensus clinical diagnoses with Cox proportional hazards regression. Results:Among 1,271 participants, models revealed no significant differences in progression over time but did reveal significantly lower baseline ADAS-Cog score, indicating better cognition at a given age in those with self-reported cancer history. Cox models indicated those with self-reported cancer history had significantly later age of AD onset (HR: 0.67, 95% CI: 0.53–0.85) after adjustment for covariates. Conclusion:Participants with self-reported cancer history entered ADNI with better cognition and later age of AD onset, but progressed similarly to participants without such history, indicating differences in AD between those with and without self-reported cancer history emerge early in the disease course. Such differences in longitudinal progression by self-reported cancer history could affect AD trials and observational studies, given the current focus on early disease course. Further investigation is warranted with detailed longitudinal assessment of cancer and AD.

Keywords: Alzheimer’s disease, cancer, cognitive impairment, disease progression, mild cognitive impairment

DOI: 10.3233/JAD-200108

Journal: Journal of Alzheimer's Disease, vol. 76, no. 2, pp. 691-701, 2020