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The association between plasma and MRI biomarkers in dementia with lewy bodies
Carmen Peña-Bautista1,2, Katharina Bolsewig3, Maria C Gonzalez4,5,6
1Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, NEO floor 7th, Stockholm, Huddinge, 141 83, SE, Sweden.
Background:
The diagnosis of Dementia with Lewy Bodies (DLB) is primarily based on clinical features. The main driver of DLB is alpha-synuclein-related pathology, but cerebrovascular disease (CVD) and Alzheimer's Disease (AD) co-pathologies are often found in patients with DLB. Fluid biomarkers and magnetic resonance imaging (MRI) can provide mechanistic and diagnostic information beyond clinical features. Therefore, the aim of this study was to investigate the association of plasma biomarkers (GFAP, NfL, Aβ42/40, pTau231, pTau181) with MRI markers of neurodegeneration and CVD in DLB and in patients with AD as a control group. We also evaluated the ability of biomarkers and clinical features to discriminate between DLB and AD.
Methods:
We included 134 patients from the European DLB consortium (DLB (n = 92) and AD (n = 43)) with plasma biomarkers determined with Simoa and MRI assessed with radiological scales for medial temporal lobe atrophy (MTA), global cortical atrophy scale - frontal subscale (GCA-F), posterior atrophy (PA), and cerebrovascular disease (Fazekas scale). Associations between plasma and MRI biomarkers were assessed with the Mann-Whitney U test, and group differences and the discrimination between DLB and AD were assessed with ANCOVA, Random Forest, and ROC analyses.
Results:
In DLB, plasma concentrations of GFAP and NfL were associated with MTA, GCA-F, and Fazekas scale; and the Aβ42/40 ratio was associated with PA and Fazekas. Most of these associations were not statistically significant in AD. Individually, plasma and MRI biomarkers had a limited ability to discriminate DLB from AD. Plasma biomarkers helped increase the low specificity of core clinical features from 68% up to 79%, keeping the high sensitivity of 90%.
Conclusions:
Plasma biomarkers of AD co-pathology, glial processes and unspecific neurodegeneration are associated with MRI biomarkers of atrophy and cerebrovascular disease in DLB patients. Plasma biomarkers increase the ability of core clinical features to discriminate between DLB and AD.
Insights
Plasma biomarkers like GFAP and NfL correlate with MRI findings in Dementia with Lewy Bodies (DLB). These biomarkers improve the diagnostic accuracy of clinical assessments for differentiating DLB from Alzheimer's Disease (AD).
Area of Science:
- Neuroscience
- Biomarker Research
- Neuroimaging
Background:
- Dementia with Lewy Bodies (DLB) diagnosis relies on clinical features, often with co-pathologies like Alzheimer's Disease (AD) and cerebrovascular disease (CVD).
- Fluid biomarkers and MRI offer additional diagnostic and mechanistic insights beyond clinical evaluation.
- Investigating plasma biomarkers and MRI markers is crucial for understanding DLB pathology and improving diagnosis.
Purpose of the Study:
- To examine the associations between plasma biomarkers (GFAP, NfL, Aβ42/40, pTau231, pTau181) and MRI markers of neurodegeneration and CVD in DLB.
- To compare these associations in DLB patients versus AD patients.
- To assess the diagnostic discrimination between DLB and AD using biomarkers and clinical features.
Main Methods:
- Included 134 patients (92 DLB, 43 AD) from the European DLB consortium.
- Plasma biomarkers measured using Simoa; MRI assessed for medial temporal lobe atrophy (MTA), global cortical atrophy (GCA-F), posterior atrophy (PA), and Fazekas scale.
- Statistical analyses included Mann-Whitney U test, ANCOVA, Random Forest, and ROC analyses.
Main Results:
- In DLB, GFAP and NfL correlated with MTA, GCA-F, and Fazekas scale; Aβ42/40 ratio associated with PA and Fazekas.
- Most associations were not significant in AD.
- Plasma biomarkers improved specificity for differentiating DLB from AD when combined with clinical features (from 68% to 79%), maintaining high sensitivity (90%).
Conclusions:
- Plasma biomarkers reflect AD co-pathology, glial activation, and neurodegeneration, correlating with MRI markers of atrophy and CVD in DLB.
- Plasma biomarkers enhance the diagnostic performance of clinical features for distinguishing DLB from AD.
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