Subregional volumes of the hippocampus in relation to cognitive function and risk of dementia

Background: Total hippocampal volume has been consistently linked to cognitive function and dementia. Yet, given its complex and parcellated internal structure, the role of subregions of the hippocampus in cognition and risk of dementia remains relatively underexplored. We studied subregions of the hippocampus in a large population-based cohort to further understand their role in cognitive impairment and dementia risk. Methods: We studied 5035 dementia- and stroke-free persons from the Rotterdam Study, aged over 45 years. All participants underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Automatic segmentation of the hippocampus and 12 of its subregions was performed using the FreeSurfer software (version 6.0). A cognitive test battery was performed, and participants were followed up for the development of dementia until 2015. Associations of hippocampal subregion volumes with cognition and incident dementia were examined using linear and Cox regression models, respectively. All analyses were adjusted for age, sex, education, and total hippocampal volume. Results: Mean age was 64.3 years (SD 10.6) with 56% women. Smaller volumes of the hippocampal fimbria, presubiculum and subiculum showed the strongest associations with poor performance on several cognitive domains, including executive function but not memory. During a mean follow-up of 5.5 years, 76 persons developed dementia. Smaller subiculum volume was associated with risk of dementia adjusted for total volume (hazard ratio per SD decrease in volume: 1.75, 95% confidence interval 1.35; 2.26). Conclusions: In a community-dwelling non-demented population, we describe patterns of association between hippocampal subregions with cognition and risk of dementia. Specifically, the subiculum was associated with both poorer cognition and higher risk of dementia.