There is increasing evidence of a relationship between underweight or obesity and dementia risk. Several studies have investigated the relationship between body weight and brain atrophy, a pathological change preceding dementia, but their results are inconsistent. Therefore, we aimed to evaluate the relationship between body mass index (BMI) and cortical atrophy among cognitively normal participants.

We recruited cognitively normal participants (n = 1,111) who underwent medical checkups and detailed neurologic screening, including magnetic resonance imaging (MRI) in the health screening visits between September 2008 and December 2011. The main outcome was cortical thickness measured using MRI. The number of subjects with five BMI groups in men/women was 9/9, 148/258, 185/128, 149/111, and 64/50 in underweight, normal, overweight, mild obesity, and moderate to severe obesity, respectively. Linear and non-linear relationships between BMI and cortical thickness were examined using multiple linear regression analysis and generalized additive models after adjustment for potential confounders.

Among men, underweight participants showed significant cortical thinning in the frontal and temporal regions compared to normal weight participants, while overweight and mildly obese participants had greater cortical thicknesses in the frontal region and the frontal, temporal, and occipital regions, respectively. However, cortical thickness in each brain region was not significantly different in normal weight and moderate to severe obesity groups. Among women, the association between BMI and cortical thickness was not statistically significant.

Our findings suggested that underweight might be an important risk factor for pathological changes in the brain, while overweight or mild obesity may be inversely associated with cortical atrophy in cognitively normal elderly males.

Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD).

We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years).

As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD.

Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.