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Meta-Analysis of Neurochemical Changes Estimated via Magnetic Resonance Spectroscopy in Mild Cognitive Impairment and Alzheimer's Disease

ABSTRACT: The changes of neurochemicals in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients has been observed via magnetic resonance spectroscopy in several studies. However, whether it exists the consistent pattern of changes of neurochemicals in the encephalic region during the progression of MCI to AD were still not clear. The study performed meta-analysis to investigate the patterns of neurochemical changes in the encephalic region in the progress of AD. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases, and finally included 63 studies comprising 1,086 MCI patients, 1,256 AD patients, and 1,907 healthy controls. It showed that during the progression from MCI to AD, N-acetyl aspartate (NAA) decreased continuously in the posterior cingulate (PC) (SMD: −0.42 [95% CI: −0.62 to −0.21], z = −3.89, P < 0.05), NAA/Cr (creatine) was consistently reduced in PC (SMD: −0.58 [95% CI: −0.86 to −0.30], z = −4.06, P < 0.05) and hippocampus (SMD: −0.65 [95% CI: −1.11 to −0.12], z = −2.44, P < 0.05), while myo-inositol (mI) (SMD: 0.44 [95% CI: 0.26–0.61], z = 4.97, P < 0.05) and mI/Cr (SMD: 0.43 [95% CI: 0.17–0.68], z = 3.30, P < 0.05) were raised in PC. Furthermore, these results were further verified by a sustained decrease in the NAA/mI of PC (SMD: −0.94 [95% CI: −1.24 to −0.65], z = −6.26, P < 0.05). Therefore, the levels of NAA and mI were associated with the cognitive decline and might be used as potentially biomarkers to predict the possible progression from MCI to AD. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020200308.

SUBMITTER: Liu H

PROVIDER: S-EPMC8569809 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo detect changes in brain lateralization in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) using resting-state functional magnetic resonance imaging (fMRI).Materials and methodsData from 61 well-matched right-handed subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative, including 19 healthy controls (HCs), 25 patients with MCI, and 17 patients with AD. First, we divided 256 pairs of seed regions from each hemisphere covering the entire cerebral gray matter. Then, we used the intrinsic laterality index (iLI) approach to quantify the functional laterality using fMRI. One-way ANOVA was employed to estimate the differences in iLI among the three groups. The sum, number and mean value of the iLI were calculated within the thresholds of 0?<?|iLI|?<?0.2, 0.2???|iLI|?<?0.4, 0.4???|iLI|?<?0.8, and |iLI|???0.8, to explore the changes in the lateralization of resting-state brain function in patients with MCI and AD.ResultsOne-way ANOVA revealed that the iLIs of the three groups were significantly different. The HCs showed a significant leftward interhemispheric difference within |iLI|???0.8. Compared with the HCs, the patients with MCI manifested a distinct abnormal rightward interhemispheric asymmetry, mainly within the thresholds of 0.2???|iLI|?<?0.4 and 0.4???|iLI|?<?0.8; in the patients with AD, the normal leftward lateralization that was observed in the HCs disappeared, and an abnormal rightward laterality was expressed within 0.4???|iLI|?<?0.8. By directly comparing the patients with MCI with the patients with AD, an exclusive abnormal rightward laterality was observed in the patients with MCI within the 0.2???|iLI|?<?0.4 threshold, and the normal leftward asymmetry vanished in the patients with AD within the |iLI|???0.8 threshold.ConclusionGlobal brain lateralization was different among three groups. The abnormal rightward dominance observed in the patients with MCI and AD may indicate that these patients use additional brain resources to compensate for the loss of cognitive function, and the observed disappearance of the leftward laterality in the patients with AD was likely associated with the damage in the left hemisphere. The observed disappearance of the rightward asymmetry in the patients with AD using the 0.2???|iLI|?<?0.4 threshold was likely a sign of decompensation. Our study provides new insights that may improve our understanding of MCI and AD.

Project description:BackgroundMild cognitive impairment (MCI) of an amnestic type is a common condition in older people and highly predictive of Alzheimer's disease (AD). To date, there is no clear consensus regarding the best antecedent biomarker to predict early conversion to AD.ObjectiveThe aim of the study is to demonstrate that (1)H magnetic resonance spectroscopy (MRS) of the brain in MCI patients may predict early conversion to dementia within the 2-year period after baseline assessment.MethodsA cohort of patients fulfilling the criteria of amnestic MCI were enrolled consecutively. At baseline the patients underwent neuropsychological examination, standard blood tests and APOE genotype. (1)H-MRS (1.5 T) of the brain was carried out by exploring two areas: the posteromedial bilateral parietal lobe and left medial occipital lobe. The patients were followed up to detect conversion to probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association group criteria.ResultsAfter a 2-year follow-up, 27 (38%) patients converted to AD. The mean N-acetyl-aspartate/creatine (NAA/Cr) ratio in the posteromedial bilateral parietal cortex was 1.38 in converters versus 1.49 in non-converters (p<0.0001). An NAA/Cr ratio equal to or lower than 1.43 in this area predicted conversion to probable AD at 74.1% sensitivity and 83.7% specificity (area under the curve: 0.84; 95% CI 0.73 to 0.92). The cross-validated accuracy of classification was 82%, which reaches 85% when the APOE4 genotype and memory test are included in the analysis. In the left medial occipital lobe, the predictive value was somewhat lower with 85.2% sensitivity and 61.4% specificity (area under the curve: 0.8; 95% CI 0.69 to 0.89). Neither the APOE4 genotype nor leuco-araiosis was predictive of conversion to dementia.ConclusionMRS is a valuable biomarker to predict early conversion to dementia in patients with amnestic MCI.

Project description:Several magnetic resonance imaging studies have shown that the entorhinal cortex (ERC) is the first brain area related to pathologic changes in Alzheimer's disease (AD), even before atrophy of the hippocampus (HP). However, change in ERC morphology (thickness, surface area and volume) in the progression from aMCI to AD, especially in the subtypes of aMCI (single-domain and multiple-domain: aMCI-s and aMCI-m), however, is still unclear. ERC thickness, surface area and volume were measured in 29 people with aMCI-s, 22 people with aMCI-m, 18 patients with AD and 26 age-/sex-matched healthy controls. Group comparisons of the ERC geometry measurements (including thickness, volume and surface area) were performed using analyses of covariance (ANCOVA). Furthermore, receiver operator characteristic (ROC) analyses and the area under the curve (AUC) were employed to investigate classification ability (HC, aMCI-s, aMCI-m and AD from each other). There was a significant decreasing tendency in ERC thickness from HC to aMCI-s to aMCI-m to finally AD in both the left and the right hemispheres (left hemisphere: HC > aMCI-s > AD; right hemisphere: aMCI-s > aMCI-m > AD). For ERC volume, both the AD group and the aMCI-m group showed significantly decreased volume on both sides compared with the HC group. In addition, the AD group also had significantly decreased volume on both sides compared with the aMCI-s group. As for the ERC surface area, no significant difference was identified among the four groups. Furthermore, the AUC results demonstrate that combined ERC parameters (thickness and volume) can better discriminate the four groups from each other than ERC thickness alone. Finally, and most importantly, relative to HP volume, the capacity of combined ERC parameters was better at discriminating between HC and aMCI-s, as well as aMCI-m and AD. ERC atrophy, particularly the combination of ERC thickness and volume, might be regarded as a promising candidate biomarker in the diagnosis and differential diagnosis of aMCI and AD.

Project description:A sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential monitoring marker, in patients with amnestic mild cognitive impairment, according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen amnestic mild cognitive impairment patients underwent magnetic resonance imaging and 18FDG-positron emission tomography scans both at inclusion and 18 months later. Baseline and follow-up positron emission tomography data were corrected for partial volume effects and spatially normalized using magnetic resonance imaging data, scaled to the vermis and compared using SPM2. 'PET-PAC' maps reflecting metabolic per cent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than non-converters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-positron emission tomography for monitoring early Alzheimer's disease progression.

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Meta-Analysis of Neurochemical Changes Estimated via Magnetic Resonance Spectroscopy in Mild Cognitive Impairment and Alzheimer's Disease

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