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Predictive Scale for Amyloid PET Positivity Based on Clinical and MRI Variables in Patients with Amnestic Mild Cognitive Impairment.

ABSTRACT: The presence of amyloid-β (Aβ) deposition is considered important in patients with amnestic mild cognitive impairment (aMCI), since they can progress to Alzheimer's disease dementia. Amyloid positron emission tomography (PET) has been used for detecting Aβ deposition, but its high cost is a significant barrier for clinical usage. Therefore, we aimed to develop a new predictive scale for amyloid PET positivity using easily accessible tools. Overall, 161 aMCI patients were recruited from six memory clinics and underwent neuropsychological tests, brain magnetic resonance imaging (MRI), apolipoprotein E (APOE) genotype testing, and amyloid PET. Among the potential predictors, verbal and visual memory tests, medial temporal lobe atrophy, APOE genotype, and age showed significant differences between the Aβ-positive and Aβ-negative groups and were combined to make a model for predicting amyloid PET positivity with the area under the curve (AUC) of 0.856. Based on the best model, we developed the new predictive scale comprising integers, which had an optimal cutoff score ≥ 3. The new predictive scale was validated in another cohort of 98 participants and showed a good performance with AUC of 0.835. This new predictive scale with accessible variables may be useful for predicting Aβ positivity in aMCI patients in clinical practice.

SUBMITTER: Chun MY

PROVIDER: S-EPMC9224873 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Predictive Scale for Amyloid PET Positivity Based on Clinical and MRI Variables in Patients with Amnestic Mild Cognitive Impairment.

Chun Min Young MY Kim Geon Ha GH Park Hee Kyung HK Yang Dong Won DW Kim SangYun S Choi Seong Hye SH Jeong Jee Hyang JH

Journal of clinical medicine 20220615 12

The presence of amyloid-β (Aβ) deposition is considered important in patients with amnestic mild cognitive impairment (aMCI), since they can progress to Alzheimer's disease dementia. Amyloid positron emission tomography (PET) has been used for detecting Aβ deposition, but its high cost is a significant barrier for clinical usage. Therefore, we aimed to develop a new predictive scale for amyloid PET positivity using easily accessible tools. Overall, 161 aMCI patients were recruited from six memor ...[more]

PMID: 35743503

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Project description:IntroductionPrevious studies have examined the predictive accuracy of plasma amyloid beta (Aβ) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of Aβ precursor protein 669-711/Aβ1-42, Aβ1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI).MethodsThis prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow-up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged ≥ 65 years with MCI at baseline. Plasma Aβ biomarkers were analyzed using immunoprecipitation-mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma Aβ markers were examined using multiple linear regression analysis. Associations of plasma biomarkers with clinical conversion to Alzheimer's disease (AD) dementia were evaluated using Kaplan‒Meier curves.ResultsThe participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0-80.0] years). Plasma biomarkers correlated with cortical amyloid uptake (ρ = 0.667-0.754). The composite biomarker had the best area under the curve (0.943, 95% confidence interval [CI]: 0.901 to 0.985) for predicting amyloid positivity. Apolipoprotein ε4 status showed significant correlations with increased plasma amyloid biomarker levels. Participants with high composite biomarker levels at baseline had a greater risk of conversion to AD dementia (hazard ratio 10.74, 95% CI: 3.51 to 32.84, P < 0.001). The higher composite biomarker was associated with a faster rate of cognitive decline (ρ = -0.575, P < 0.001).DiscussionPlasma Aβ composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community-based cohort.HighlightsPlasma amyloid beta (Aβ) biomarkers correlated with 11C-Pittsburgh compound B uptake, mainly in the frontal/parietotemporal cortices and posterior cingulate gyrus.The amyloid composite biomarker can predict amyloid positron emission tomography positivity with a high area under the curve of 0.943 in a community-based mild cognitive impairment cohort.The higher amyloid composite biomarker at baseline was significantly associated with worsening Mini-Mental State Examination score and a high risk for developing Alzheimer's disease (AD) dementia over 8 years.The amyloid composite biomarker can predict clinical progression to AD dementia with a high area under the curve of 0.860.Apolipoprotein E ε4 status influenced the plasma Aβ biomarker levels.

Project description:BackgroundMild cognitive impairment in Parkinson's disease (PD-MCI) is associated with faster cognitive decline and conversion to dementia. There is uncertainty about the role of β-amyloid (Aβ) co-pathology and its contribution to the variability in PD-MCI profile and cognitive progression.ObjectiveTo study how presence of Aβ affects clinical and cognitive manifestations as well as regional brain volumes in PD-MCI.MethodsTwenty-five PD-MCI patients underwent simultaneous PET/3T-MRI with [18F]flutemetamol and a clinical and neuropsychological examination allowing level II diagnosis. We tested pairwise differences in motor, clinical, and cognitive features with Mann-Whitney U test. We calculated [18F]flutemetamol (FMM) standardized uptake value ratios (SUVR) in striatal and cortical ROIs, and we performed a univariate linear regression analysis between the affected cognitive domains and the mean SUVR. Finally, we investigated differences in cortical and subcortical brain regional volumes with magnetic resonance imaging (MRI).ResultsThere were 8 Aβ+ and 17 Aβ- PD-MCI. They did not differ for age, disease duration, clinical, motor, behavioral, and global cognition scores. PD-MCI-Aβ+ showed worse performance in the overall executive domain (p = 0.037). Subcortical ROIs analysis showed significant Aβ deposition in PD-MCI-Aβ+ patients in the right caudal and rostral middle frontal cortex, in precuneus, in left paracentral and pars triangularis (p < 0.0001), and bilaterally in the putamen (p = 0.038). Cortical regions with higher amyloid load correlated with worse executive performances (p < 0.05). Voxel-based morphometry (VBM) analyses showed no between groups differences.ConclusionsPresence of cerebral Aβ worsens executive functions, but not motor and global cognitive abilities in PD-MCI, and it is not associated with middle-temporal cortex atrophy. These findings, together with the observation of significant proportion of PD-MCI-Aβ-, suggest that Aβ may not be the main pathogenetic determinant of cognitive deterioration in PD-MCI, but it would rather aggravate deficits in domains vulnerable to Parkinson primary pathology.

Dataset Information

Predictive Scale for Amyloid PET Positivity Based on Clinical and MRI Variables in Patients with Amnestic Mild Cognitive Impairment.

Publications

Predictive Scale for Amyloid PET Positivity Based on Clinical and MRI Variables in Patients with Amnestic Mild Cognitive Impairment.

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