Although memory is commonly affected in elderly healthy subjects, neuroimaging studies seeking for age related hippocampal volume loss have been controversial. One reason for this might be that the hippocampus is not homogenous but consists of histologically and functionally different subfields which might be differently affected by age. 1. To test for global age related gray and white matter volume changes. 2. To test if hippocampal age effects are global or subfield specific. 45 cognitively normal controls (aged 21–85, mean 54.5±17.4, m/f: 27/18) were studied on a 4T magnet with the following sequences: 1. Volumetric T1–weighted gradient echo MRI (MPrage) resolution 1 × 1 × 1 mm. 2. High resolution T2–weighted fast spin echo 0.4 × 0.5 × 2 mm resolution, 2, angulated perpendicular to the long axis of the hippocampus. The MPrage was segmented into gray (GM) and white maps (WM) which were used for optimized voxel–based–morphometry (VBM) in SPM2. The entorhinal cortex (ERC), subiculum, CA1, CA2 and CA3/4/dentate–compound were marked on the high resolution image on 5 consecutive slices using anatomical landmarks. The influence of age, gender and total intracranial volume on hippocampal subfields was tested using linear regression and regionally unbiased tests for age related GM/WM reductions were performed using SPM2. VBM showed age related GM reductions bilaterally in hippocampus, putamen, thalamus, cerebellum, operculum, anterior and posterior cingulate and parieto–occipital and frontal cortex while WM reductions were found in corona radiata, corpus callosum, and periventricular, temporal and frontal WM. Significant negative age effects were found for ERC (p>0.005) and CA1 (p<0.00001) and significant age and gender effects (p<0.025) for CA2 which was primarily driven by volume loss in men. Neither CA1 nor ERC volume loss was correlated with GM losses after correction for age effects. Healthy aging is associated with regionally restricted volume loss that involves cortical regions incl. ERC. In the hippocampus age effects are restricted to specific subfields, notably CA1 while others, e.g. subiculum, are less affected. This regionally distinct pattern of atrophic changes, particularly also in the hippocampus, may have diagnostic value for early detection of Alzheimer's disease.
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