Abstract
Epidemiological studies show a reciprocal inverse association between cancer and Alzheimer's disease (AD). The common mechanistic theory for this effect posits that cells have an innate tendency toward apoptotic or survival pathways, translating to increased risk for either neurodegeneration or cancer. However, it has been shown that cancer patients experience cognitive dysfunction pre- and post-treatment as well as alterations in cerebral gray matter density (GMD) on MRI. To further investigate these issues, we analyzed the association between cancer history (CA±) and age of AD onset, and the relationship between GMD and CA± status across diagnostic groups in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort study. Data was analyzed from 1609 participants with information on baseline cancer history and AD diagnosis, age of AD onset, and baseline MRI scans. Participants were CA+ (N = 503) and CA− (N = 1106) diagnosed with AD, mild cognitive impairment (MCI), significant memory concerns (SMC), and cognitively normal older adults. As in previous studies, CA+ was inversely associated with AD at baseline (P = 0.025); interestingly, this effect appears to be driven by non-melanoma skin cancer (NMSC), the largest cancer category in this study (P = 0.001). CA+ was also associated with later age of AD onset (P < 0.001), independent of apolipoprotein E (APOE) ε4 allele status, and individuals with two prior cancers had later mean age of AD onset than those with one or no prior cancer (P < 0.001), suggesting an additive effect. Voxel-based morphometric analysis of GMD showed CA+ had lower GMD in the right superior frontal gyrus compared to CA− across diagnostic groups (Pcrit < 0.001, uncorrected); this cluster of lower GMD appeared to be driven by history of invasive cancer types, rather than skin cancer. Thus, while cancer history is associated with a measurable delay in AD onset independent of APOE ε4, the underlying mechanism does not appear to be cancer-related preservation of GMD.
Highlights
Multiple epidemiological studies have identified a significant inverse association between cancer and Alzheimer’s disease (AD), primarily in white non-Hispanic cohorts (Tirumalasetti et al, 1991; Desouky, 1992; Yamada et al, 1999; Roe et al, 2005, 2010; Driver et al, 2012; Realmuto et al, 2012; Musicco et al, 2013)
While previous studies have indicated that this inverse association is mediated by age, our results are the first to quantify the later age of AD onset associated with cancer history, as well as to suggest that this effect may be additive, as the small group of individuals with a history of multiple cancers showed later age of AD onset compared to individuals with a history of one or no cancers
SEER data indicates that breast and prostate cancer are the most common cancer types, followed by colorectal cancer and melanoma
Summary
Multiple epidemiological studies have identified a significant inverse association between cancer and Alzheimer’s disease (AD), primarily in white non-Hispanic cohorts (Tirumalasetti et al, 1991; Desouky, 1992; Yamada et al, 1999; Roe et al, 2005, 2010; Driver et al, 2012; Realmuto et al, 2012; Musicco et al, 2013). The cancers represented in most of these study populations were highly heterogeneous, suggesting that rather than specific cancer effects, such as estrogen deprivation in breast cancer, the inverse association between cancer and AD is likely due to strong underlying biological mechanisms. Identification of these biological mechanisms may provide direction to future therapeutic efforts, for AD, as there is currently a significant lack of effective treatments for this disease
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