Mackenzie E Fowler1, Kristen L Triebel2, Gary R Cutter3, Lon S Schneider4, Richard E Kennedy5. 1. Department of Epidemiology, University of Alabama, Birmingham, Birmingham, AL, USA. 2. Division of Neuropsychology, Department of Neurology, University of Alabama, Birmingham, Birmingham, AL, USA. 3. Department of Biostatistics, University of Alabama, Birmingham, Birmingham, AL, USA. 4. University of Southern California Keck School of Medicine, Los Angeles, CA, USA. 5. Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama, Birmingham, Birmingham, AL, USA.
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.
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.
Authors: R C Petersen; P S Aisen; L A Beckett; M C Donohue; A C Gamst; D J Harvey; C R Jack; W J Jagust; L M Shaw; A W Toga; J Q Trojanowski; M W Weiner Journal: Neurology Date: 2009-12-30 Impact factor: 9.910
Authors: C M Roe; A L Fitzpatrick; C Xiong; W Sieh; L Kuller; J P Miller; M M Williams; R Kopan; M I Behrens; J C Morris Journal: Neurology Date: 2009-12-23 Impact factor: 9.910
Authors: Jane A Driver; Alexa Beiser; Rhoda Au; Bernard E Kreger; Greta Lee Splansky; Tobias Kurth; Douglas P Kiel; Kun Ping Lu; Sudha Seshadri; Phillip A Wolf Journal: BMJ Date: 2012-03-12
Authors: Mackenzie E Fowler; Nicole C Wright; Kristen Triebel; Gabrielle B Rocque; Marguerite R Irvin; Richard E Kennedy Journal: J Alzheimers Dis Date: 2022 Impact factor: 4.160