The effect of hippocampal subfield volumes on cognitive decline and incident dementia in a memory clinic cohort

BackgroundThe hippocampus plays a central role in cognition and hippocampal atrophy is a key hallmark of Alzheimer's disease. Evidence has suggested associations between hippocampal subfield volumes and specific cognitive domains and dementia risk. However, to our knowledge, no study has examined the role of hippocampal subfield volumes in cognitive decline across different domains over time.ObjectiveWe investigated associations between hippocampal subfield volumes and changes in cognitive domains together with incident dementia in a memory clinic cohort.MethodsAssociations between hippocampal subfield volumes and cognitive decline over three years (<i>n </i>= 443) were analyzed using generalized estimating equations, and associations with incident dementia (<i>n </i>= 283) using multiple logistic regression.ResultsAt baseline, all hippocampal subfield volumes were associated with diagnosis of dementia, while the CA4-dentate gyrus, molecular layer, subicular complex, and fimbria volumes were associated with diagnosis of CIND. Over three years, all subfields except the hippocampal fissure were associated with memory. Decreased molecular layer (OR:2.26, 95%CI:1.50;3.50) size was associated with increased risk of dementia.ConclusionsOur findings suggest that hippocampal atrophy of the cornu ammonis, CA4-dentate gyrus, and molecular layer may first manifest with cognitive impairment in memory before other subfields of the hippocampus, and that molecular layer volume may be an early biomarker of dementia. Further research demonstrating the biological role of hippocampal subfields in specific cognitive domains is required.