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Association of cancer history with Alzheimer's disease onset and structural brain changes.

Nudelman KN, Risacher SL, West JD, McDonald BC, Gao S, Saykin AJ, Alzheimer's Disease Neuroimaging Initiati - Front Physiol (2014)

Bottom Line: 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.Voxel-based morphometric analysis of GMD showed CA+ had lower GMD in the right superior frontal gyrus compared to CA- across diagnostic groups (P crit < 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, IN, USA ; Training in Research for Behavioral Oncology and Cancer Control, Indiana University School of Nursing Indianapolis, IN, USA ; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA.

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 (P crit < 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.

No MeSH data available.


Related in: MedlinePlus

Percent of individuals with cancer history (CA+) per diagnostic group. There are significant differences in CA+ (blue striped bars) compared to individuals without cancer history (CA−, red dotted bars) between Alzheimer's disease (AD) diagnostic groups (P = 0.025), including cognitively normal controls (CN), and individuals with significant memory concerns (SMC), mild cognitive impairment (MCI), and AD. There is a smaller percentage of AD CA+, and a larger percentage of SMC CA+, compared to the CN CA+ percentage, while the MCI CA+/CA− ratio does not appear to be significantly different than CN CA+/CA−.
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Figure 2: Percent of individuals with cancer history (CA+) per diagnostic group. There are significant differences in CA+ (blue striped bars) compared to individuals without cancer history (CA−, red dotted bars) between Alzheimer's disease (AD) diagnostic groups (P = 0.025), including cognitively normal controls (CN), and individuals with significant memory concerns (SMC), mild cognitive impairment (MCI), and AD. There is a smaller percentage of AD CA+, and a larger percentage of SMC CA+, compared to the CN CA+ percentage, while the MCI CA+/CA− ratio does not appear to be significantly different than CN CA+/CA−.

Mentions: Chi-Square analysis indicated that CA+ was significantly associated with AD diagnostic group at baseline (χ2 = 9.4, P = 0.025). As seen in Figure 2 and Table 4, fewer study participants with AD are CA+ compared to other diagnostic groups. Interestingly, individuals with SMC are more evenly divided between CA+ and CA− than other groups.


Association of cancer history with Alzheimer's disease onset and structural brain changes.

Nudelman KN, Risacher SL, West JD, McDonald BC, Gao S, Saykin AJ, Alzheimer's Disease Neuroimaging Initiati - Front Physiol (2014)

Percent of individuals with cancer history (CA+) per diagnostic group. There are significant differences in CA+ (blue striped bars) compared to individuals without cancer history (CA−, red dotted bars) between Alzheimer's disease (AD) diagnostic groups (P = 0.025), including cognitively normal controls (CN), and individuals with significant memory concerns (SMC), mild cognitive impairment (MCI), and AD. There is a smaller percentage of AD CA+, and a larger percentage of SMC CA+, compared to the CN CA+ percentage, while the MCI CA+/CA− ratio does not appear to be significantly different than CN CA+/CA−.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215790&req=5

Figure 2: Percent of individuals with cancer history (CA+) per diagnostic group. There are significant differences in CA+ (blue striped bars) compared to individuals without cancer history (CA−, red dotted bars) between Alzheimer's disease (AD) diagnostic groups (P = 0.025), including cognitively normal controls (CN), and individuals with significant memory concerns (SMC), mild cognitive impairment (MCI), and AD. There is a smaller percentage of AD CA+, and a larger percentage of SMC CA+, compared to the CN CA+ percentage, while the MCI CA+/CA− ratio does not appear to be significantly different than CN CA+/CA−.
Mentions: Chi-Square analysis indicated that CA+ was significantly associated with AD diagnostic group at baseline (χ2 = 9.4, P = 0.025). As seen in Figure 2 and Table 4, fewer study participants with AD are CA+ compared to other diagnostic groups. Interestingly, individuals with SMC are more evenly divided between CA+ and CA− than other groups.

Bottom Line: 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.Voxel-based morphometric analysis of GMD showed CA+ had lower GMD in the right superior frontal gyrus compared to CA- across diagnostic groups (P crit < 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, IN, USA ; Training in Research for Behavioral Oncology and Cancer Control, Indiana University School of Nursing Indianapolis, IN, USA ; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine Indianapolis, IN, USA.

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 (P crit < 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.

No MeSH data available.


Related in: MedlinePlus