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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

Lower gray matter density (GMD) with cancer history across diagnostic groups. (A) Surface rendering shows individuals with a history of cancer (CA+) display lower GMD than individuals without cancer history (CA−), across diagnostic groups, in the right superior frontal gyrus (cluster maximum MNI coordinates 28, 32, 54), shown circled (Punc < 0.001, cluster threshold Punc ≤ 0.1); this effect is observed to be bilateral at a more lenient threshold (Punc < 0.01, cluster threshold Punc ≤ 0.1), shown above. Colored areas indicate regions where CA+ gray matter density was less than CA− across groups at this threshold; red to yellow color scale indicates increasing statistical significance, with yellow areas indicating the most significant regions. (B) GMD values for right superior frontal gyrus cluster graphed by CA+ (red dotted bars) and CA− (blue striped bars) across AD diagnostic groups; CA+ have lower GMD across diagnostic groups.
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Figure 4: Lower gray matter density (GMD) with cancer history across diagnostic groups. (A) Surface rendering shows individuals with a history of cancer (CA+) display lower GMD than individuals without cancer history (CA−), across diagnostic groups, in the right superior frontal gyrus (cluster maximum MNI coordinates 28, 32, 54), shown circled (Punc < 0.001, cluster threshold Punc ≤ 0.1); this effect is observed to be bilateral at a more lenient threshold (Punc < 0.01, cluster threshold Punc ≤ 0.1), shown above. Colored areas indicate regions where CA+ gray matter density was less than CA− across groups at this threshold; red to yellow color scale indicates increasing statistical significance, with yellow areas indicating the most significant regions. (B) GMD values for right superior frontal gyrus cluster graphed by CA+ (red dotted bars) and CA− (blue striped bars) across AD diagnostic groups; CA+ have lower GMD across diagnostic groups.

Mentions: As noted above, a linear model of GMD deficits in AD, MCI, and SMC groups compared to CN was used to confirm that groups further along the AD spectrum display lower GMD. As expected, lower GMD was observed for affected groups throughout the brain, consistent with prior work (Risacher et al., 2009, 2010). Modeling the opposite relationship, with higher GMD in the AD group compared to other groups, showed no significant regions of greater GMD in the AD group. A second VBM analysis examined all groups irrespective of AD diagnosis, to identify regions that were increased or decreased in CA+ compared to CA−. This model showed that CA+ had lower GMD in the right superior frontal gyrus compared to CA− (peak-level Punc < 0.001, cluster-level Punc ≤ 0.1; Figure 4A). There were no regions of significantly greater GMD in CA+ at this threshold. As seen in Figure 4B, CA+ showed significantly lower GMD in the right superior frontal gyrus cluster across diagnostic 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)

Lower gray matter density (GMD) with cancer history across diagnostic groups. (A) Surface rendering shows individuals with a history of cancer (CA+) display lower GMD than individuals without cancer history (CA−), across diagnostic groups, in the right superior frontal gyrus (cluster maximum MNI coordinates 28, 32, 54), shown circled (Punc < 0.001, cluster threshold Punc ≤ 0.1); this effect is observed to be bilateral at a more lenient threshold (Punc < 0.01, cluster threshold Punc ≤ 0.1), shown above. Colored areas indicate regions where CA+ gray matter density was less than CA− across groups at this threshold; red to yellow color scale indicates increasing statistical significance, with yellow areas indicating the most significant regions. (B) GMD values for right superior frontal gyrus cluster graphed by CA+ (red dotted bars) and CA− (blue striped bars) across AD diagnostic groups; CA+ have lower GMD across diagnostic groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Lower gray matter density (GMD) with cancer history across diagnostic groups. (A) Surface rendering shows individuals with a history of cancer (CA+) display lower GMD than individuals without cancer history (CA−), across diagnostic groups, in the right superior frontal gyrus (cluster maximum MNI coordinates 28, 32, 54), shown circled (Punc < 0.001, cluster threshold Punc ≤ 0.1); this effect is observed to be bilateral at a more lenient threshold (Punc < 0.01, cluster threshold Punc ≤ 0.1), shown above. Colored areas indicate regions where CA+ gray matter density was less than CA− across groups at this threshold; red to yellow color scale indicates increasing statistical significance, with yellow areas indicating the most significant regions. (B) GMD values for right superior frontal gyrus cluster graphed by CA+ (red dotted bars) and CA− (blue striped bars) across AD diagnostic groups; CA+ have lower GMD across diagnostic groups.
Mentions: As noted above, a linear model of GMD deficits in AD, MCI, and SMC groups compared to CN was used to confirm that groups further along the AD spectrum display lower GMD. As expected, lower GMD was observed for affected groups throughout the brain, consistent with prior work (Risacher et al., 2009, 2010). Modeling the opposite relationship, with higher GMD in the AD group compared to other groups, showed no significant regions of greater GMD in the AD group. A second VBM analysis examined all groups irrespective of AD diagnosis, to identify regions that were increased or decreased in CA+ compared to CA−. This model showed that CA+ had lower GMD in the right superior frontal gyrus compared to CA− (peak-level Punc < 0.001, cluster-level Punc ≤ 0.1; Figure 4A). There were no regions of significantly greater GMD in CA+ at this threshold. As seen in Figure 4B, CA+ showed significantly lower GMD in the right superior frontal gyrus cluster across diagnostic 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