FDG PET evidence suggests the left insula may be a hub for cognitive reserve in mild cognitive impairment

Cognitive reserve (CR) refers to the ability to cope with the detrimental effects of ageing or brain pathology on cognition. Individuals with higher CR may maintain cognitive performance despite a greater burden of underlying brain pathology. This study aimed to characterize cerebral metabolic patterns associated with CR in subjects with amnestic mild cognitive impairment (aMCI) using [18]F-FDG PET/CT, and to identify brain regions associated with higher CR. Sixty-three subjects with aMCI were included in this cross-sectional study. Based on the Cognitive Reserve Index questionnaire (CRIq), 29 participants were classified as having high CR (HCR) and 34 as having low CR (LCR). Brain [18]F-FDG PET/CT scans were obtained in all participants and compared with those of 19 cognitively healthy subjects (HS). Voxel-wise analyses and volume-of-interest analyses were performed to assess regional metabolic differences, and multivariable regression models evalu- ated the association between CRIq and insular metabolism after adjustment for age and sex. Both HCR and LCR groups exhibited the characteristic temporo-parietal pattern of Alzheimer’s disease-related hypometabo- lism compared with HS. Direct voxel-wise comparison between HCR and LCR identified a significant differ- ence in the left anterior insula, where metabolism was relatively preserved in HCR. Left insular metabolism was positively associated with CRIq score independently of age and sex. These findings suggest that relatively preserved left insular metabolism is associated with higher CR in aMCI and identify the left anterior insula as a candidate neural substrate of CR. Future longitudinal studies will be important to confirm these findings and clarify the mechanisms possibly linking left insular metabolism to CR.