Abstract

Post-mortem studies indicate that subfields of the hippocampal formation are differentially affected by normal aging and Alzheimer's Disease (AD). Recent studies on 3-4Tesla MRI confirm these observations, but mostly assessed the subfields only in the body of the hippocampus or assessed only three subfields. We developed and validated a protocol using isotropic voxels (0.70 mm 3) at 7T MRI to delineate subfields of the hippocampal formation along its full length. In this pilot study using this protocol, we examined whether subfield volumes differ between patients with Mild Cognitive Impairment (MCI)/AD and older persons with normal cognition. 17 patients (59% women) with MCI (n = 10) or AD (n = 7) were recruited at the UMC Utrecht and 17 elders (65% women) with normal cognition were recruited through GPs in the region. Subjects were scanned with a T2 sequence on a 7T MRI whole body scanner (Philips Healthcare). One rater (LEMW) manually outlined the Entorhinal Cortex (ERC), subiculum (SUB), Cornu Ammonis 1 (CA1), CA2, CA3, Dentate Gyrus (DG) & CA4 and the tail of the left hippocampal formation from coronal images, blinded to group allocation. Intracranial Volume (ICV) was assessed using unified segmentation as implemented in SPM8 (Ashburner&Friston, 2005). Subfield volumes were transformed to z-scores. Mean ± SD age was 74 ± 8 years in MCI/AD patients, and 68 ± 3 in controls. Mean MMSE scores were 25 ± 3 and 29 ± 1, respectively. Regression analyses, adjusted for age, sex and ICV, with z-scores of subfield volumes as dependent variable showed (borderline) significant differences between patients and controls for CA1 (B = -0.88, 95%CI -1.50 to -0.26; P = 0.007), DG&CA4 (B = -0.87, 95%CI -1.56 to -0.19; P = 0.014), CA3 (B = -0.80, 95%CI -1.60 to 0.001; P = 0.050), and SUB (B = -0.77, 95% CI -1.49 to -0.049; P = 0.037). No significant differences in subfield volumes were found for ERC (B = -0.34, 95%CI -1.11 to 0.43; P = 0.38), CA2 (B = -0.50, 95%CI -1.28 to 0.29; P = 0.21), and tail (B = 0.01, 95%CI -0.81 to 0.83; P = 0.98).

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