Abstract
The influence of Body Mass Index (BMI) on neurodegeneration in dementia has yet to be elucidated. We aimed at exploring the effects of BMI levels on cerebral resting-state metabolism and brain connectivity, as crucial measures of synaptic function and activity, in a large group of patients with Alzheimer’s Dementia (AD) (n = 206), considering gender. We tested the correlation between BMI levels and brain metabolism, as assessed by 18F-FDG-PET, and the modulation of the resting-state functional networks by BMI. At comparable dementia severity, females with high BMI can withstand a lower degree of brain metabolism dysfunction, as shown by a significant BMI-brain metabolism correlation in the temporal-parietal regions, which are typically vulnerable to AD pathology (R = 0.269, p = 0.009). Of note, high BMI was also associated with reduced connectivity in frontal and limbic brain networks, again only in AD females (p < 0.05 FDR-corrected, k = 100 voxels). This suggests a major vulnerability of neural systems known to be selectively involved in brain compensatory mechanisms in AD females. These findings indicate a strong gender effect of high BMI and obesity in AD, namely reducing the available reserve mechanisms in female patients. This brings to considerations for medical practice and health policy.
Highlights
The interaction between Body Mass Index (BMI) and cognition in healthy status, and the role of BMI as a risk factor for dementia are complex and highly debated issues[1,2,3]
We tested for differences in brain hypometabolism in Alzheimer’s Dementia (AD) patients with low BMI vs. high BMI, separately for female and male subgroups (p < 0.05 FWE corrected for multiple comparison, cluster extent (k) threshold at 100 voxels)
The results showed a less severe and extended pattern of hypometabolism in the high BMI compared to the low BMI female subgroup and no differences between the male BMI subgroups (Fig. 1b,c)
Summary
The interaction between Body Mass Index (BMI) and cognition in healthy status, and the role of BMI as a risk factor for dementia are complex and highly debated issues[1,2,3]. Life experiences such as high education[17,18,19], occupation[17,18] and bilingualism[20] are known to be involved in the modulation of cognitive reserve inducing brain plasticity and structural changes in both healthy subjects and patients with neurodegenerative conditions[16] These proxies of cognitive reserve seem to be crucial for processes related to the brain maintenance, leading to protection of brain integrity in aging and disease, and resulting in a higher brain reserve[16]. We studied a large group of patients with probable Alzheimer’s Dementia (AD), who underwent 18F-FDG-PET, in order to assess the effects of BMI levels on brain metabolism and connectivity, crucial measures of synaptic function and activity, while considering the role of gender
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