ATROPHY OF HIPPOCAMPAL-FORMATION SUBDIVISIONS CORRELATES WITH STAGE AND DURATION OF ALZHEIMER-DISEASE

The hippocampal formations of 13 subjects with severe Alzheimer diseas e [AD; Global Deterioration Scale (GDS) stage 7] and of 5 age-matched subjects without symptoms of dementia were reconstructed from serial s ections. Functional assessment staging (FAST) was used at the time of demise to assess 9 patients at stages 7a-c (incipient averbal and nona mbulatory) and 4 patients at stages 7e-f(immobile). The duration of th e disease from FAST stage 5 until demise ranged from 2 to 8 years in t he first of these subgroups, and from 10 to 13 years in the second. Th e volumes of the entire hippocampal formation and of the cornu ammonis , its sectors and layers, the dentate gyrus, the subicular complex, an d the entorhinal cortex were calculated. Hippocampal formation volume decreased by 36% in the incipient averbal and nonambulatory patients a nd by 60% in the severely functionally impaired immobile patients, in comparison with controls. In the final substages of AD, immobile patie nts exhibited significant atrophy, in comparison with controls, in the cornu ammonis and all of its sectors and layers except CA4, the subic ular complex and all of its parts, and the entorhinal cortex (p < 0.05 ). Within the AD patient group, significant correlations were noted be tween both the magnitude of functional severity and the duration of AD and the volumes of most hippocampal formation subdivisions studied. F or the cornu ammonis, subicular complex, and entorhinal cortex, volume tric loss correlations with FAST stage 7 ordinally enumerated substage s were r = -0.71, -0.79, and -0.62, respectively. Calculations project ed a decrease of 60% in the volume of the hippocampal formation over t he duration of clinically manifest AD (from GDS and FAST stage 3 until demise). The projected decreases in the volumes of the cornu ammonis, subicular complex, and entorhinal cortex over the duration of AD were 64, 70, and 51%, respectively. We conclude that continuing changes oc cur in the hippocampal formation and most of its structural components throughout the clinical course of AD. These changes in the volume of the hippocampal subdivisions correlate with the stage and the duration of AD but not with age at onset of the disease.