Sex-Specific regional brain activity and cognitive function in mild cognitive impairment: An rs-fMRI study

Mild cognitive impairment (MCI) is widely recognized as an early stage of dementia. Epidemiological studies suggest that MCI is more prevalent in females than in males. Notably, there are sex differences in MCI-related brain changes. Resting-state functional magnetic resonance imaging (rs-fMRI) offers a valuable method for assessing brain activity during rest. This study aims to explore sex-specific regional brain activity in participants with MCI during resting states. 86 MCI participants (21 males and 65 females) and 107 normal controls (NCs) (38 males and 69 females) were included in the present study. Regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF), and fractional ALFF (fALFF) were used to assess brain activity. MCI females showed increased ReHo values in the right cerebellum inferior compared to NC females and MCI males. However, MCI males exhibited increased ReHo values in the left hippocampus compared to NC males and MCI females. ReHo values in the right cerebellum inferior were associated with visuospatial skills in MCI males, and language function in MCI females. Additionally, ReHo values in the left hippocampus were associated with attention function in MCI females but not in MCI males. In MCI participants, sex moderated the relationship between ReHo values in the right cerebellum inferior and cognitive function (visuospatial skills and language function), as well as the association between ReHo values in the left hippocampus and attention function. In conclusions, this study revealed sex differences in ReHo of right inferior cerebellum and left hippocampus in MCI, and the association between ReHo and cognitive impairment in MCI differs by sex. These sex-specific patterns of regional brain activity can aid in the development of sex-specific precision medicine.