Associations of demyelination in the right middle temporal gyrus and right praecuneus with visuospatial cognitive dysfunction in Alzheimer's disease

Background: Alzheimer's disease (AD) is associated with impairments in not only memory but also visuospatial cognitive function. Despite its adverse effects on the quality of life, patients with early-stage AD are often neglected. Emerging evidence suggests that patients with AD exhibit increased vulnerability of myelin, a crucial component for neuronal conduction and survival. To test our hypothesis that myelin damage was associated with cognitive deficits in AD, we examined correlations of myelin integrity, quantified by T1-weighted/T2-weighted (T1w/T2w) ratios, with visuospatial cognitive abilities and compared them between patients with AD and cognitively normal (CN) individuals. Methods: Fifty-seven patients with AD and 22 CN subjects were enrolled in this study. To assess subjects' visuo-constructive abilities, we employed the Rey-Osterrieth Complex Figure Copy Test (ROCFT-c) paired with analysis of T1- and T2-weighted magnetic resonance imaging brain images. Voxel-based associations between T1w/T2w ratios and ROCFT-c scores in the AD group were assessed, controlling for age and handedness (voxel threshold uncorrected P < 0.001, cluster threshold uncorrected P < 0.05). Additionally, we compared the T1w/T2w ratios of these identified brain regions between the AD and CN groups. Results: The voxel-based analysis demonstrated positive correlations between T1w/T2w ratios and ROCFT-c scores in the right middle temporal gyrus and right praecuneus in patients with AD who exhibited significantly lower T1w/T2w ratios in the right middle temporal gyrus (P = 0.038) and a trend toward lower T1w/T2w ratios in the right praecuneus (P = 0.055). Conclusions: Our results demonstrated a strong association between reduced myelin integrity in the right middle temporal gyrus and right praecuneus and visuospatial cognitive dysfunction in patients with AD. These findings are believed to shed light on the neural basis of visuospatial processing in patients with AD, underlining the necessity for developing objective biomarkers for assessing patients' visuospatial cognitive function.