Abstract
BackgroundDementia 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.MethodsWe 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.ResultsWe 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.ConclusionsThis 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.
Highlights
Dementia with Lewy bodies (DLB) includes various core clinical features that result in different pheno‐ types
Very few studies have directly addressed the biological heterogeneity in DLB, there is an increasing interest in how Alzheimer’s disease (AD)related pathology contributes to clinical presentation in DLB
Our preliminary data suggest the possibility that these different subtypes may have their own disease trajectories, and may need to be managed differently due to distinct combinations of core clinical features and concomitant AD and cerebrovascular pathologies
Summary
Dementia with Lewy bodies (DLB) includes various core clinical features that result in different pheno‐ types. Alzheimer’s disease (AD) and cerebrovascular pathologies are common in DLB All this increases the heterogeneity within DLB and hampers clinical diagnosis. Abdelnour et al Alzheimer’s Research & Therapy (2022) 14:14 be present: parkinsonism, recurrent visual hallucinations, cognitive fluctuations, and/or rapid eye movement (REM) sleep behavior disorder (RBD) [1] These core clinical features often manifest in different combinations at the time of diagnosis or during the course of the disease, increasing the clinical heterogeneity within probable DLB. Previous studies have addressed part of this heterogeneity by investigating subgroups of patients with certain core clinical features or different rates of clinical progression [2, 3] Extending these analyses to biological features of the disease is warranted to elucidate the pathophysiology underlying the heterogeneity within probable DLB.
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