AbstractBackgroundThe hippocampal formation is considered to be one of the first brain structures affected in Alzheimer’s disease. High resolution brain MRI has made it possible to visualize the subfields of the hippocampal formation in greater detail. We estimated volumes of hippocampal subfields on 7T MRI in normal aging and early Alzheimer’s disease. We hypothesized that the subfields were differentially affected in normal cognition, subjective memory impairment, Mild Cognitive Impairment (MCI) and Alzheimer’s disease.MethodWe included 336 participants (68±9 years; 35% women) from memory clinics and from existing cohorts (SMART‐MR study and PREDICT‐MR study), and participants without dementia and MCI recruited from medical files from general practices, all of whom had 7T brain MRI using the same scan protocol. Using ASHS, hippocampal subfields (entorhinal cortex, subiculum, CA1, CA2, CA3, CA4/dentate gyrus, and tail) were segmented. Participants were categorized as having normal cognition (n=175), subjective memory impairment (n=66), cognitive impairment or MCI (n=75), and Alzheimer’s disease (n=20). General linear models with multivariate outcomes (Z‐scores of hippocampal subfield volumes) were estimated across cognitive groups, and adjusted for age, sex and intracranial volume.ResultIn the total study sample, subfield volumes (left and right hemisphere summed) (mm3) were 817±167 for entorhinal cortex, 1143±181 for subiculum, 2923±382 for CA1, 117±23 for CA2, 195±47 for CA3, 1547±245 for CA4/DG, and 284±69 for the tail. Compared to all other groups, Alzheimer’s disease patients had significantly smaller subfield volumes (p<0.05 for all subfields). Participants with cognitive impairment or MCI had smaller CA1 and CA4/dentate gyrus (p<0.05), compared to normal cognition, but not other subfields. Participants with subjective memory impairment did not differ significantly from the group with normal cognition (Figure 1).ConclusionThis study suggests that in MCI the CA1 and CA4/dentate gyrus are primarily affected, and that all hippocampal subfields are progressively affected in Alzheimer’s disease. No volume loss was observed in participants with subjective memory impairment, potentially due to inclusion of participants with etiologies other than Alzheimer’s disease.