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Published on: December 15, 2023
Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data
Carla Abdelnour1,2, Daniel Ferreira3, Marleen van de Beek4
1Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya-Barcelona, Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. carla.abdelnour@gmail.com.
Insights
Researchers identified four distinct subgroups within Dementia with Lewy bodies (DLB) patients, revealing variations in biological, clinical, and demographic features to improve diagnosis and treatment strategies for this complex neurodegenerative disease.
Area of Science:
- Neuroscience
- Neurology
- Geriatrics
Background:
- Dementia with Lewy bodies (DLB) presents heterogeneous clinical features, often co-occurring with Alzheimer's disease (AD) and cerebrovascular pathologies, complicating diagnosis.
- This heterogeneity poses challenges for accurate clinical diagnosis and targeted therapeutic interventions in DLB patients.
Purpose of the Study:
- To address the heterogeneity in DLB by identifying distinct patient subgroups based on biological, clinical, and demographic characteristics.
- To investigate potential correlations between identified subgroups and specific pathological markers and clinical presentations.
Main Methods:
- Utilized Factorial Analysis of Mixed Data (FAMD) on 107 extensively phenotyped DLB patients to identify key data dimensions.
- Employed hierarchical clustering analysis based on FAMD dimensions to subgroup patients according to biological, clinical, and demographic features.
- Included assessment of sex, age, education, disease duration, MMSE, CSF AD biomarkers, DLB core features, and regional brain atrophy.
Main Results:
- Identified 3 FAMD dimensions explaining 38% of the variance, leading to the definition of 4 distinct patient clusters.
- Cluster 1: Characterized by amyloid-β and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations.
- Cluster 2: Exhibited posterior atrophy, lowest frequency of visual hallucinations/fluctuations, and worst cognitive performance.
- Cluster 3: Showcased highest tau pathology, posterior atrophy, and low parkinsonism frequency.
- Cluster 4: Presented with normal AD biomarkers, minimal atrophy/cerebrovascular pathology, and highest MMSE scores.
Conclusions:
- Demonstrated the existence of distinct subgroups within DLB patients, each with unique biological, clinical, and demographic profiles.
- These findings hold significant implications for refining DLB diagnosis, predicting prognosis, and optimizing patient selection for clinical trials and treatment strategies.
Background:
Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer's disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features.
Methods:
We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions.
Results:
We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-β and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores.
Conclusions:
This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials.
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