Gender differences in healthy aging and Alzheimer's Dementia: A 18 F-FDG-PET study of brain and cognitive reserve

Abstract

Cognitive reserve (CR) and brain reserve (BR) are protective factors against age-associated cognitive decline and neurodegenerative disorders. Very limited evidence exists about gender effects on brain aging and on the effect of CR on brain modulation in healthy aging and Alzheimer's Dementia (AD). We investigated gender differences in brain metabolic activity and resting-state network connectivity, as measured by ¹⁸ F-FDG-PET, in healthy aging and AD, also considering the effects of education and occupation. The clinical and imaging data were retrieved from large datasets of healthy elderly subjects (HE) (225) and AD patients (282). In HE, males showed more extended age-related reduction of brain metabolism than females in frontal medial cortex. We also found differences in brain modulation as metabolic increases induced by education and occupation, namely in posterior associative cortices in HE males and in the anterior limbic-affective and executive networks in HE females. In AD patients, the correlations between education and occupation levels and brain hypometabolism showed gender differences, namely a posterior temporo-parietal association in males and a frontal and limbic association in females, indicating the involvement of different networks. Finally, the metabolic connectivity in both HE and AD aligned with these results, suggesting greater efficiency in the posterior default mode network for males, and in the anterior frontal executive network for females. The basis of these brain gender differences in both aging and AD, obtained exploring cerebral metabolism, metabolic connectivity and the effects of education and occupation, is likely at the intersection between biological and sociodemographic factors. Hum Brain Mapp 38:4212-4227, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: Alzheimer's Dementia; Fluorine-18-Flourodeoxiglucose; brain reserve; cognitive reserve; education; gender; healthy aging; occupation; positron emission tomography.

Figure 1

Aging effect in healthy elderly female and male groups. Left: Results of negative SPM linear correlations between age and ¹⁸F‐FDG‐PET glucose metabolism in females (pink) and males (blue). Correlations are shown at P < 0.05 with FWE correction for multiple comparisons. Right: Function representations of age (x‐axis) and brain metabolism (y‐axis) in females (pink) and males (blue), obtained by Generalized Additive Model analysis. Continuous lines: estimate functions between age and brain metabolism; Dashed lines: 2 standard errors above and below the estimate function. Abbreviations: ROI = region of interest; FDG‐PET = positron emission tomography imaging with Fluorine‐18‐Flourodeoxiglucose. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Healthy elderly groups. Positive correlations between education (A) and occupation (B) and ¹⁸F‐FDG‐PET glucose metabolism in females (pink) and males (blue). Correlations are represented in MRIcron at P < 0.01 uncorrected to show all gender differences in this explorative voxel‐based analysis (see Supporting Information Table 2 for anatomical details and level of significance). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Patients with Alzheimer's Dementia. Negative correlations between education (A) and occupation (B) and ¹⁸F‐FDG‐PET glucose metabolism in females (pink) and males (blue). Correlations are represented in MRIcron at P < 0.01 uncorrected to show all gender differences in this explorative voxel‐based analysis (see Supporting Information Table 3 for anatomical details and level of significance). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Brain metabolic connectivity results. Healthy elderly subjects (A, C, E) and patients with Alzheimer's Dementia (B, D, F). Females (pink), males (blue), and overlap (violet). From top to bottom: dorsal Default Mode Network (seeds: posterior cingulum/precuneus); Executive Control Network (seeds: middle frontal and superior frontal gyri); Language Network (seeds: left angular, middle, and superior temporal gyri). All the results are shown at P < 0.01 FDR. [Color figure can be viewed at http://wileyonlinelibrary.com]