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A Metallomic Approach to Assess Associations of Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: An Exploratory Study.

ABSTRACT: Alzheimer's disease (AD) involves the abnormal activity of transition metals and metal ion dyshomeostasis; however, the potential of trace metal biomarkers in predicting cognitive decline has not been evaluated. This study aimed to assess the potential of 36 trace elements in predicting cognitive decline in patients with amnestic mild cognitive impairment (aMCI) or AD. Participants (9 controls, 23 aMCI due to AD, and 8 AD dementia) underwent comprehensive cognitive tests, including the Mini-Mental State Examination (MMSE) and trace metal analysis. The correlations between the plasma trace element levels and annual MMSE changes during follow-up were analyzed. We found that an increase in disease severity was linked to lower plasma levels of boron (B), bismuth (Bi), thorium (Th), and uranium (U) (adjusted p < 0.05). Higher baseline calcium levels (r = 0.50, p = 0.026) were associated with less annual cognitive decline; those of B (r = -0.70, p = 0.001), zirconium (r = -0.58, p = 0.007), and Th (r = -0.52, p = 0.020) with rapid annual cognitive decline in the aMCI group; and those of manganese (r = -0.91, p = 0.035) with rapid annual cognitive decline in the AD group. Overall, our exploratory study suggests that plasma metal levels have great potential as in vivo biomarkers for aMCI and AD. Larger sample studies are necessary to confirm these results.

SUBMITTER: Lin YK

PROVIDER: S-EPMC9267221 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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A Metallomic Approach to Assess Associations of Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: An Exploratory Study.

Lin Yu-Kai YK Liang Chih-Sung CS Tsai Chia-Kuang CK Tsai Chia-Lin CL Lee Jiunn-Tay JT Sung Yueh-Feng YF Chou Chung-Hsing CH Shang Hung-Sheng HS Yang Bing-Heng BH Lin Guan-Yu GY Su Ming-Wei MW Yang Fu-Chi FC

Journal of clinical medicine 20220624 13

Alzheimer’s disease (AD) involves the abnormal activity of transition metals and metal ion dyshomeostasis; however, the potential of trace metal biomarkers in predicting cognitive decline has not been evaluated. This study aimed to assess the potential of 36 trace elements in predicting cognitive decline in patients with amnestic mild cognitive impairment (aMCI) or AD. Participants (9 controls, 23 aMCI due to AD, and 8 AD dementia) underwent comprehensive cognitive tests, including the Mini-Ment ...[more]

PMID: 35806940

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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.

Project description:BackgroundAlzheimer's disease (AD) is characterized by progressive cognitive decline and specific brain atrophy patterns, primarily involving the medial temporal lobes. A number of studies have discussed hypothalamic involvement in AD with consecutive metabolic and/or autonomic disturbances yet only few studies have investigated hypothalamic atrophy in AD and its early stages in particular.MethodsWe applied semi-automated volumetry of the hypothalamus (HTH) in 3 T MRI in a sample N = 175 participants [age 74.9 ± 7.22; gender 85 m/90f; cognitively normal controls (CN; N = 56); amnestic mild cognitive impairment (MCI; N = 78); AD (N = 41)] from the Alzheimer's Disease Neuroimaging Initiative (ADNI). In addition, we used voxel-based morphometry (VBM), cortical thickness (CTH) analyses and source-based morphometry (SBM) derived networks of structural covariance to investigate brain structural covariance patterns of the HTH under consideration of diagnostic groups, β-amyloid (AB) positivity and apolipoprotein E (APOE) ε4 status.ResultsHypothalamic atrophy was observed in both early and advanced disease stages (i.e. hypothalamic volume CN > MCI > AD). VBM, CTH analysis and SBM revealed positive associations between hypothalamic volume (HV) and AD-vulnerable regions, largely corresponding to the Papez circuit and brain regions implicated in autonomic regulation, however, group differences regarding HTH structural covariance were not observed. Similar observations were made in carriers and non-carriers of the ε4 allele, yet more pronounced in ε4 carriers. Although not reaching significance, comparisons of AB positive vs. negative subjects indicated stronger HTH atrophy in biomarker positive participants. HV was not associated with body mass index or longitudinal weight change.ConclusionsOur findings support early structural changes of the HTH in AD. HV covaries with regional volumes of AD-vulnerable regions. This could point to secondary atrophy of the HTH following atrophy of the hippocampus and other structures of the Papez circuit in AD.

Dataset Information

A Metallomic Approach to Assess Associations of Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: An Exploratory Study.

Publications

A Metallomic Approach to Assess Associations of Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: An Exploratory Study.

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