Resting State Connectivity in Posterior Cingulate and Hippocampus in Mild Alzheimer’s

Abstract

Proton Magnetic Resonance Spectroscopy (1H MRS) has been proposed as a diagnostic tool in the early phase of dementia. The main metabolites measured with this technique are N-acetylaspartate (NAA), myoinositol (mI), choline (Cho) and creatine (Cr). NAA is a sensitive marker for neuronal density and viability; increased mI levels correlate with glial proliferation; Cho is associated with membrane breakdown and turnover, Cr is commonly used to normalize metabolite values. In this study we measured these metabolites in the posterior cingulate gyrus and in the medial occipital lobe in a large number of cognitively healthy elderly, subjects with amnesic mild cognitive impairment (MCI) and patients with mild (CDR = 1) Alzheimer's disease (AD). All subjects underwent double voxel 1H MRS at 1.5 T. 1H MR spectroscopy voxels of 8 cm3 (2x2x2 cm) were placed over the posterior cingulate gyrus and the medial occipital lobe. An echo time of 35 ms and repetition time of 2000 ms were used in acquisitions from the VOIs. Mean NAA/Cr value measured in posterior cingulate based voxel was 1.45±0.08 in healthy controls, 1.40±0.08 in MCI subjects and 1.36±0.11 in AD patients. mI/Cr raised from controls and MCI to AD (0.66±0.08 in controls, 0.66±0.15 in MCI, 0.71±0.10 in AD). Reduction in NAA/mI ratio was found in AD patients compared to MCI and controls (2.23±0.43 in controls, 2.03±0.35 in MCI, 1.94±0.32 in AD). After adjustment for age and gender, mI/Cr was significantly higher in AD patients compared to MCI and the difference between AD and MCI was still significant after adjusting for age and gender (p<0.01). Diagnosis of MCI was still associated with higher posterior cingulate NAA/mI ratio compared to AD (ß (SE)= 0.25 (0.12), p < 0.05). Mean values differences of metabolites in medial occipital lobe among groups were not statistically significant. Our findings confirm that 1H MR spectroscopy is a useful diagnostic tool in dementia, mostly in the posterior cingulate gyrus, that can be explained with the regional neuropathological alteration commonly observed in AD (plaques and tangles) that typically affects limbic cortical regions in the early stage of the disease. Further analysis will be necessary to confirm these results that however highlight the diagnostic value of 1H MR, whose great potential in this field is still to be expressed.