Diaschisis-Like Association of Hippocampal Atrophy and Posterior Cingulate Cortex Hypometabolism in Cognitively Normal Elderly Depends on Impaired Integrity of Parahippocampal Cingulum Fibers.

Hippocampal atrophy and hypometabolism of the posterior cingulate cortex (PCC), early markers of Alzheimer's disease (AD), have been shown to be associated in late mild cognitive impairment and early AD via atrophy of connecting cingulum fibers. Recently, a direct association of hippocampal atrophy and PCC hypometabolism has been shown in cognitively normal elderly. We aimed to investigate if this association might be modulated by partly non-hippocampogenic alterations of parahippocampal cingulum (PHC) integrity. 45 cognitively healthy elderly aged 59 to 89 years were included from the Alzheimer's Disease Neuroimaging Initiative. Hippocampal volumes and PCC glucose metabolism were measured using MRI and FDG-PET. PHC fibers connecting the hippocampus and the PCC were reconstructed using diffusion weighted MRI and measures of diffusivity were calculated. Using robust linear regression, interaction effects of PHC diffusivity and hippocampal volume on PCC metabolism were calculated. For both hemispheres, significant interaction effects were found for PHC mean diffusivity. Interaction effects were such that the association of hippocampal volume and PCC metabolism was higher in subjects with increased mean diffusivity in PHC fibers. In cognitively normal elderly, compromised integrity of the PHC may increase the risk of PCC hypometabolism due to hippocampal atrophy. Spared PHC fiber integrity may protect against PCC hypometabolism due to hippocampal atrophy.