MRI of hippocampal volume loss in early Alzheimers disease in relation to ApoE genotype and biomarkers

Hippocampal volume change over time, measured with MRI, has huge potential as a marker for Alzheimers disease. The objectives of this study were: (i) to test if constant and accelerated hippocampal loss can be detected in Alzheimers disease, mild cognitive impairment and normal ageing over short periods, e.g. 612 months, with MRI in the large multicentre setting of the Alzheimers Disease Neuroimaging Initiative (ADNI); (ii) to determine the extent to which the polymorphism of the apolipoprotein E (ApoE) gene modulates hippocampal change; and (iii) to determine if rates of hippocampal loss correlate with cerebrospinal fluid (CSF) biomarkers of Alzheimers disease, such as the -amyloid (A(142)) and tau proteins (tau). The MRI multicentre study included 112 cognitive normal elderly individuals, 226 mild cognitive impairment and 96 Alzheimers disease patients who all had at least three successive MRI scans, involving 47 different imaging centres. The mild cognitive impairment and Alzheimers disease groups showed hippocampal volume loss over 6 months and accelerated loss over 1 year. Moreover, increased rates of hippocampal loss were associated with presence of the ApoE allele 4 gene in Alzheimers disease and lower CSF A(142) in mild cognitive impairment, irrespective of ApoE genotype, whereas relations with tau were only trends. The power to measure hippocampal change was improved by exploiting correlations statistically between successive MRI observations. The demonstration of considerable hippocampal loss in mild cognitive impairment and Alzheimers disease patients over only 6 months and accelerated loss over 12 months illustrates the power of MRI to track morphological brain changes over time in a large multisite setting. Furthermore, the relations between faster hippocampal loss in the presence of ApoE allele 4 and decreased CSF A(142) supports the concept that increased hippocampal loss is an indicator of Alzheimers disease pathology and a potential marker for the efficacy of therapeutic interventions in Alzheimers disease.