Age-Related Sex-Specific Changes in Brain Metabolism and Morphology

Abstract

With a large database, we aimed to evaluate sex-specific distinctive changes in brain glucose metabolism and morphology during normal aging using MRI and 18 F-FDG PET. Methods: A total of 963 cognitively healthy adults were included in this study. All subjects completed a medical questionnaire, took the mini-mental state examination, and underwent brain MRI and whole-body 18 F-FDG PET. The MR and PET images were statistically analyzed using 3-dimensional stereotactic surface projection. All images were corrected for whole-brain pixel value to identify the brain regions with significant changes, and regions of interest were set up with reference to Brodmann areas. We evaluated morphologic and glucose metabolic changes by cross-sectional analysis. The baseline database consisted of subjects from 30 to 40 y old, and the age-step for comparison was 5-y ranges. We also compared sex-specific differences in MR and PET images in each age group. Results: Regarding age-related changes, in both sexes brain atrophy was observed in the lateral frontal and parietal regions and glucose hypometabolism in the medial frontal regions. There were significant differences in these parameters between the sexes; parallel changes in volume and metabolism were manifested in the medial frontal cortex in men and in the lateral and medial temporal cortex in women. By contrast, metabolism-dominant reductions were manifested in the lateral and medial parietal cortex in men and in the ventrolateral prefrontal cortex, including the Broca area, in women. These differences became insignificant in individuals 66 y or older. Conclusion: Our brain mapping study with a large number of reference human brain data demonstrated age-related parallel changes between morphology and metabolism in the medial frontal regions and sex-specific hypometabolism in the parietal (male) and ventrolateral prefrontal (female) cortices. These findings may suggest an aging vulnerability in sex-specific brain regions: the parietal cortex for visuospatial ability in men and the Broca area for speech processing in women. The current trend of an increase in the number of dementia patients, including those with Alzheimer disease (AD) (1), as well as the revised criteria for the diagnosis of dementia by the National Institute on Aging and the Alzheimer's Association (2-5), has brought researchers to place greater attention on early, preclinical, detection of changes in brain physiology. Indeed, in familial AD, pathologic changes in the brain seem to develop 25 y before the onset of clinical symptoms (6).To detect the preclinical stage of AD, it is necessary to catch subtle deviations from the healthy brain and, thus, to know the morphology and activity of a healthy brain for comparison. Several studies have used MRI or PET on cognitively normal people to evaluate age-related changes and sex-specific differences in the brain. To the best of our knowledge, however, the sexspecific differences in brain morphology and metabolism found by previous brain imaging studies were only in ...

Sleep and Human Aging

“…Fourth, older adult men experience more accelerated gray matter atrophy in the core NREM slow wave generating region of the medial prefrontal cortex (Kakimoto et al, 2016; Murphy et al, 2009), which is the same cortical region in which atrophy predicts the severity of SWA decline in the elderly in general (Figure 5) (Mander et al, 2013). Moreover, older adult males suffer greater reductions in metabolic activity in the medial prefrontal regions similar to the medial prefrontal SWA-source generating regions, implicating a functional impairment that may even precede the greater medial prefrontal gray matter atrophy observed in men (Kakimoto et al, 2016).…”

“…Moreover, older adult males suffer greater reductions in metabolic activity in the medial prefrontal regions similar to the medial prefrontal SWA-source generating regions, implicating a functional impairment that may even precede the greater medial prefrontal gray matter atrophy observed in men (Kakimoto et al, 2016). Independently or collectively, these regionally and functionally specific possibilities all lead to falsifiable predictions regarding the mechanisms of gender differences in sleep deterioration in later life.…”

Magnetic resonance imaging and positron emission tomography in the diagnosis of neurodegenerative dementias

“…In normal subjects, [ 18 F]FDG PET is able to detect a progressive and diffuse reduction of regional consumption of glucose that parallels advancing atrophy (mainly in the frontal, temporal and parietal areas) and age. Even in the absence of cortical atrophy, a progressive reduction of metabolism in the mesial frontal region can be detected, with possible gender differences (Kakimoto et al, 2016). Note the low uptake in the primary visual cortex, which suggests a diagnosis of DLB.…”

Tactics for preclinical validation of receptor-binding radiotracers

“…For instance, a large [ 18 F]-FDG PET study consisting of 493 men and 470 women spanning 5 decades (32 – 87 years) showed lower metabolism in parietal cortex for men compared to women, while lower metabolism was observed in ventrolateral prefrontal cortex for women compared to men [215]. In a multi-institutional study of nonischemic heart failure, three radiotracers, [ 15 O]-H 2 O, [ 11 C]-palmitate and [ 11 C]-glucose, were used to evaluate myocardial blood flow and metabolism [216].…”