Statin is associated with higher cortical thickness in early Alzheimer's disease

Background: The brain is the most cholesterol-rich organ, essential for myelination and neuronal function. Statins, widely used to lower cholesterol, cross the blood-brain barrier and may impact brain cholesterol synthesis. Despite their widespread use, the effects of statins on cortical regions relevant to Alzheimer's disease (AD) are not well understood. This study aimed to compare cortical thickness between statin-exposed and statin-unexposed older adults and evaluate the potential neuroprotective effects of statins. Methods: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The sample included 193 healthy controls (HC), 485 individuals with mild cognitive impairment (MCI), and 169 individuals with Alzheimer's disease (AD). Participants were categorized as statin users if they had used statins for at least two years. MRI data were processed using FreeSurfer software to estimate cortical thickness in 64 regions of interest. ANCOVA models assessed the association between statin use and cortical thickness at baseline, and linear mixed models evaluated longitudinal changes. Results: Statin use was associated with increased cortical thickness in multiple brain regions across HC, MCI, and AD participants. In HC, statin users had greater thickness in the right lateral occipital, left middle temporal, and left parahippocampal regions. MCI participants exhibited additional increases in the right cuneus, right posterior cingulate, and left superior temporal cortex. In AD, statin users had higher thickness in the right cuneus and right superior parietal lobule. Longitudinal analysis revealed no statin-related differences in cortical thickness changes among HC and AD groups, but in MCI, statins slowed cortical thinning in the left medial orbitofrontal cortex. Conclusion: Statin use is associated with greater cortical thickness in older adults, particularly in those with MCI. These findings suggest that statins may have neuroprotective effects, potentially mitigating neurodegenerative changes in early cognitive decline. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and understand the mechanisms involved.