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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

Categorized cancer types count out of 593 total incidences. 14 categories were created from the original 40 cancer types; most are self-explanatory, such as all types of cancer related to female organs aside from breast categorized as “Female Other.” The “Other” category contained seven types of cancer with one reported case, which did not fit into any other category. GI, gastrointestinal cancer (including colorectal cancer); NMSC, non-melanoma skin cancer.
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Figure 1: Categorized cancer types count out of 593 total incidences. 14 categories were created from the original 40 cancer types; most are self-explanatory, such as all types of cancer related to female organs aside from breast categorized as “Female Other.” The “Other” category contained seven types of cancer with one reported case, which did not fit into any other category. GI, gastrointestinal cancer (including colorectal cancer); NMSC, non-melanoma skin cancer.

Mentions: Given that previous studies used highly heterogeneous cancer populations, the distribution of cancer types in ADNI was further examined. Out of the 1609 individuals utilized in this analysis, there were 421 individuals with a history of one prior cancer, and 82 individuals with a history of multiple cancers, yielding 593 total recorded cancer incidences. Cancer types were classified into 14 categories, as shown in Figure 1 and Table 3. Although there are some differences in cancer distribution among groups, overall, cancer category percentages were not significantly different between diagnostic groups (Chi-square χ2 = 31.2, P = 0.8). Subsequent analyses investigating the inverse association of cancer and AD were therefore performed using all types of cancer unless otherwise stated.


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)

Categorized cancer types count out of 593 total incidences. 14 categories were created from the original 40 cancer types; most are self-explanatory, such as all types of cancer related to female organs aside from breast categorized as “Female Other.” The “Other” category contained seven types of cancer with one reported case, which did not fit into any other category. GI, gastrointestinal cancer (including colorectal cancer); NMSC, non-melanoma skin cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Categorized cancer types count out of 593 total incidences. 14 categories were created from the original 40 cancer types; most are self-explanatory, such as all types of cancer related to female organs aside from breast categorized as “Female Other.” The “Other” category contained seven types of cancer with one reported case, which did not fit into any other category. GI, gastrointestinal cancer (including colorectal cancer); NMSC, non-melanoma skin cancer.
Mentions: Given that previous studies used highly heterogeneous cancer populations, the distribution of cancer types in ADNI was further examined. Out of the 1609 individuals utilized in this analysis, there were 421 individuals with a history of one prior cancer, and 82 individuals with a history of multiple cancers, yielding 593 total recorded cancer incidences. Cancer types were classified into 14 categories, as shown in Figure 1 and Table 3. Although there are some differences in cancer distribution among groups, overall, cancer category percentages were not significantly different between diagnostic groups (Chi-square χ2 = 31.2, P = 0.8). Subsequent analyses investigating the inverse association of cancer and AD were therefore performed using all types of cancer unless otherwise stated.

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