Predicting conversion from mild cognitive impairment to Alzheimer's disease using brain 1H-MRS and volumetric changes: A two- year retrospective follow-up study

Abstract

This study investigated the ability of magnetic resonance spectroscopy ( 1 H-MRS) of posterior cingulate cortex (PCC) and brain volumetry to predict the progression from mild cognitive impairment (MCI) to Alzheimer's Disease (AD) on the basis of clinical classification at 2 years follow-up. Thirty-eight MCI patients, eighteen healthy older adults and twenty-three AD patients were included in this study. All participants underwent a brain-MR protocol (1.5 T GE scanner) including high-resolution T1-weighted volumetric sequence (isotropic 1mm 3 ). Voxel-wise differences in brain volumetry were evaluated using FreeSurfer software and all volumes were normalized by the total intracranial volume (TIV). Careful localization of 1 H-MRS volume of PCC was performed and data were processed with the LCModel program. MCI patients underwent a complete neuropsychological assessment at baseline and were clinically re-evaluated after a mean of 28 months; twenty-six MCI patients (68.4%) converted to AD and twelve remained stable. At baseline these two MCI subgroups did not differ in the global cognitive level (Mini Mental State Examination, MMSE) or in any of the other cognitive domains; the NAA/ mI ratio in the PCC was able to differentiate MCI converters from those MCI that did not develop AD (p = 0.022) with a level of accuracy (AUC area) of 0.779. A significantly reduced volume of parahippocampal gyrus (p = 0.010) and fusiform gyrus (p = 0.026) were found in the converter MCI subgroup compared to the stable MCI subgroup. The combined use of both N- acetyl-aspartate (NAA)/myo-Inositol (mI) ratio and volume of parahippocampal gyrus, increases the overall accuracy (AUC = 0.910) in predicting the conversion to AD two years before the development of clinical symptoms. Additional longitudinal studies with a broader representative sample of MCI patients and longer follow-up might be helpful to confirm these results and to elucidate the role of each parameter in predicting the possible progression to AD, and also to all the other non-AD dementia subtypes.

Proton Magnetic Resonance Spectroscopy in Common Dementias—Current Status and Perspectives

“…This is a particular challenge, as mild cognitive complaints caused by incipient dementia are difficult to distinguish from non-pathological ageing processes (4). Previous studies indicate that metabolic changes can be detected in preclinical (29,37,49) and MCI stages (27,38). However, in order to assess the potential use of MRS for early detection, large-scale, preferably longitudinal studies are necessary.…”

“…It is also worth taking a look at recent studies in which the clinical outcome was determined in a prospective study design, with three studies involving patients with MCI (27,30,35) and 283.0 T2,000/68 Singe-voxel AD (n=17),MCI (n=21),HC (N=15) 291.5 T2,000/25 Single-voxel Baseline: 303.0 T1,500/35 Single-voxel aMCI (n=48) + clinical follow-up after 3 years: AD (n=15), aMCI (n=33) one study involving cognitively healthy elderly individuals (29). The PCC was investigated in all studies.…”

Pineal volume reduction in patients with mild cognitive impairment who converted to Alzheimer's disease

“…The conversion rate from MCI to AD ranges from 23% to 68% for follow-up periods from 13 to 60 months. 7,9,[12][13][14][15][16] Dementia incidence in people over age 50 years with MCI is much higher than that in psychiatric outpatients of a similar age (249 vs 31 cases per 1000 person-years). 26 However, MCI has various pathologies, and not all MCI patients progress to dementia.…”

“…Neuroimaging studies have shown the brain regions associated with conversion from MCI to AD. Structural magnetic resonance imaging (MRI) has detected the temporal lobe, 7,9 medial temporal lobe, 7,10,11 hippocampus, 7,[12][13][14][15] and parahippocampal gyrus 16 as predictors of conversion, while functional neuroimaging has implied that the precuneus, 9,14 frontal cortex, 9 and temporoparietal cortex 15 are involved in conversion.…”

Early Detection of Alzheimer’s Disease: Detecting Asymmetries with a Return Random Walk Link Predictor

“…In [ 16 ], these regions are included in the list of the ten anatomical regions with the largest entropy differences between normal and AD subjects. Related work [ 31 , 32 , 33 , 34 , 35 , 36 , 44 ] has highlighted the asymmetries between right and left hemispheres of the hippocampus as one of the regions with more relevance (beside hippocampal subfields and entorhinal cortices), but they use a subset of MCI patients.…”