Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data.

Olivier Bousiges, Eric Westman, Afina W Lemstra, Dag Aarsland, Jaime Kulisevsky, Javier Pagonabarraga, Mercè Boada, Alessandro Padovani, Lars-Olof Wahlund, Andrea Pilotto, Frédéric Blanc, Lena Cavallin, Ketil Oppedal, Nira Cedres, Marleen van de Beek, Daniel Ferreira, Carla Abdelnour

Journal: Alzheimer's research & therapy 2022;14(1):14

PMID: 35063023

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Abstract

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.

Address: Research 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. [email protected].; Department of Medicine of the Universitat Autònoma de Barcelona, Barcelona, Spain. [email protected].; Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; Department of Psychology, Sensory Cognitive Interaction Laboratory (SCI-lab), Stockholm University, Stockholm, Sweden.; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.; Department of Radiology, Stavanger University Hospital, Stavanger, Norway.; Department of Electrical Engineering and Computer Science, University of Stavanger, Stavanger, Norway.; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.; Department of Radiology Karolinska University Hospital, Stockholm, Sweden.; Service, Memory Resources and Research Centre, University Hospital of Strasbourg, Strasbourg, France.; Team IMIS/Neurocrypto, French National Center for Scientific Research, ICube Laboratory and Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.; Centre Mémoire, de Ressources et de Recherche d'Alsace (Strasbourg-Colmar), Strasbourg, France.; Laboratory of Biochemistry and Molecular Biology, CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives, UMR7364, University Hospital of Strasbourg, Strasbourg, France.; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.; Research 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.; Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau. Biomedical Research Institute (IIB-Sant Pau), Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.; Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

DOI: 10.1186/s13195-021-00946-w

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MeSH Terms: Alzheimer Disease, Amyloid beta-Peptides, Cluster Analysis, Demography, Humans, Lewy Body Disease