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Associations between Plasma Biomarkers and Cognition in Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment: A Cross-Sectional and Longitudinal Study.

ABSTRACT: Brain degeneration in patients with Alzheimer's disease (AD) results from the accumulation of pathological amyloid- (A?) plaques and tau protein tangles, leading to altered plasma levels of biomarkers. However, few studies have investigated the association between plasma biomarkers and cognitive impairment in patients with AD. In this cross-sectional study, we investigated correlations between mini-mental state examination (MMSE) scores and levels of plasma biomarkers in patients with amnestic mild cognitive impairment (aMCI) and AD. Thirteen individuals with normal cognition, 40 patients with aMCI, and 37 patients with AD were enrolled. Immunomagnetic reduction was used to assess the levels of plasma biomarkers, including amyloid A1-40, A1-42, total tau protein (t-Tau), and phosphorylated tau protein (threonine 181, p-Tau181). Our analysis revealed a significant negative correlation between MMSE and both measures of tau, and a trend toward negative correlation between MMSE and A1-42. In a longitudinal study involving three patients with aMCI and two patients with AD, we observed strong negative correlations (r < -0.8) between changes in MMSE scores and plasma levels of t-Tau. Our results suggest that plasma levels of t-Tau and p-Tau181 can be used to assess the severity of cognitive impairment in patients with AD. Furthermore, the results of our preliminary longitudinal study suggest that levels of t-Tau can be used to monitor the progression of cognitive decline in patients with aMCI/AD.

SUBMITTER: Tsai CL

PROVIDER: S-EPMC6912664 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Associations between Plasma Biomarkers and Cognition in Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment: A Cross-Sectional and Longitudinal Study.

Tsai Chia-Lin CL Liang Chih-Sung CS Lee Jiunn-Tay JT Su Ming-Wei MW Lin Chun-Chieh CC Chu Hsuan-Te HT Tsai Chia-Kuang CK Lin Guan-Yu GY Lin Yu-Kai YK Yang Fu-Chi FC

Journal of clinical medicine 20191106 11

Brain degeneration in patients with Alzheimer's disease (AD) results from the accumulation of pathological amyloid- (Aβ) plaques and tau protein tangles, leading to altered plasma levels of biomarkers. However, few studies have investigated the association between plasma biomarkers and cognitive impairment in patients with AD. In this cross-sectional study, we investigated correlations between mini-mental state examination (MMSE) scores and levels of plasma biomarkers in patients with amnestic m ...[more]

PMID: 31698867

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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:The increasing burden of Alzheimer's disease (AD) emphasizes the need for effective diagnostic and therapeutic strategies. Despite available treatments targeting amyloid beta (Aβ) plaques, disease-modifying therapies remain elusive. Early detection of mild cognitive impairment (MCI) patients at risk for AD conversion is crucial, especially with anti-Aβ therapy. While plasma biomarkers hold promise in differentiating AD from MCI, evidence on predicting cognitive decline is lacking. This study's objectives were to evaluate whether plasma protein biomarkers could predict both cognitive decline in non-demented individuals and the conversion to AD in patients with MCI. This study was conducted as part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a prospective, community-based cohort. Participants were based on plasma biomarker availability and clinical diagnosis at baseline. The study included MCI (n = 50), MCI-to-AD (n = 21), and cognitively unimpaired (CU, n = 40) participants. Baseline plasma concentrations of six proteins-total tau (tTau), phosphorylated tau at residue 181 (pTau181), amyloid beta 42 (Aβ42), amyloid beta 40 (Aβ40), neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP)-along with three derivative ratios (pTau181/tTau, Aβ42/Aβ40, pTau181/Aβ42) were analyzed to predict cognitive decline over a six-year follow-up period. Baseline protein biomarkers were stratified into tertiles (low, intermediate, and high) and analyzed using a linear mixed model (LMM) to predict longitudinal cognitive changes. In addition, Kaplan-Meier analysis was performed to discern whether protein biomarkers could predict AD conversion in the MCI subgroup. This prospective cohort study revealed that plasma NFL may predict longitudinal declines in Mini-Mental State Examination (MMSE) scores. In participants categorized as amyloid positive, the NFL biomarker demonstrated predictive performance for both MMSE and total scores of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-TS) longitudinally. Additionally, as a baseline predictor, GFAP exhibited a significant association with cross-sectional cognitive impairment in the CERAD-TS measure, particularly in amyloid positive participants. Kaplan-Meier curve analysis indicated predictive performance of NFL, GFAP, tTau, and Aβ42/Aβ40 on MCI-to-AD conversion. This study suggests that plasma GFAP in non-demented participants may reflect baseline cross-sectional CERAD-TS scores, a measure of global cognitive function. Conversely, plasma NFL may predict longitudinal decline in MMSE and CERAD-TS scores in participants categorized as amyloid positive. Kaplan-Meier curve analysis suggests that NFL, GFAP, tTau, and Aβ42/Aβ40 are potentially robust predictors of future AD conversion.

Dataset Information

Associations between Plasma Biomarkers and Cognition in Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment: A Cross-Sectional and Longitudinal Study.

Publications

Associations between Plasma Biomarkers and Cognition in Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment: A Cross-Sectional and Longitudinal Study.

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