Hippocampal volume maximally modulates the relationship between subsyndromal symptomatic depression and cognitive impairment in non-demented older adults

Subsyndromal symptomatic depression (SSD) is associated with an elevated risk of cognitive impairment in non-demented older adults. Given that hippocampal and middle temporal gyrus atrophy have been shown to cause SSD, our study aimed to investigate the effect of hippocampal volume on the association between SSD and cognitive impairment.

338 non-demented older adults from the ADNI (Alzheimer's Disease Neuroimaging Initiative) cohort who underwent cognitive assessments, questionnaires on depressive symptoms and MRI brain were studied. SSD group is defined as a score of 1-5 based on Geriatric Depression Scale scores. We conducted causal mediation analyses to investigate the effect of hippocampal volume on cognitive performance cross-sectionally.

The SSD group displayed lower left and right hippocampal volume (p<0.01) than the non-SSD group. SSD was linked to poorer cognition and smaller hippocampal volume. We found that hippocampal volume partially mediated the effect of SSD on cognitive performance including the global cognition and the cognitive section of Alzheimer's Disease Assessment Scale, with mediation percentages ranging from 6.45 % to 30.46 %. In addition, we found that the thickness of the left middle temporal, right entorhinal and right fusiform gyrus, brain regions linked to AD, mediate the relationship between SSD and cognition with mediation percentages ranging from 8.67 % to 21.44 %.

Our article didn't differentiate between mild cognitive impairment and normal population.

The associations of SSD and cognitive impairment are linked to alterations in Alzheimer's Disease related brain regions.