Beatrice Orso, Ariane Bollack, Zulfiqar H Sheikh+3 more · 2025 · Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · Springer · added 2026-04-24
Dementia with Lewy Bodies (DLB) is a neurodegenerative disorder characterised by α-synuclein pathology, causing cognitive decline, motor and non-motor symptoms. This review explores the clinical and n Show more
Dementia with Lewy Bodies (DLB) is a neurodegenerative disorder characterised by α-synuclein pathology, causing cognitive decline, motor and non-motor symptoms. This review explores the clinical and neuropathological heterogeneity of DLB, which complicates its early diagnosis, prognosis, and treatment. The staging of Lewy body (LB) pathology varies, with both brain-first and body-first hypotheses suggesting different origins and pathways for disease progression. Co-pathologies, such as amyloid-β plaques, tau tangles, and cerebrovascular changes, further influence the clinical presentation and rate of disease progression in DLB patients, contributing to significant variability. In this review, the role of genetic factors, particularly APOE ε4 and GBA mutations, in shaping DLB's clinical and pathological diversity is also emphasized. Heterogeneous manifestations, including REM sleep behavior disorder (RBD), mild cognitive impairment, and psychiatric-onset DLB, highlight the need for improved biomarkers to guide early diagnosis. Neuroimaging techniques such as [ Overall, the paper explores the complexity of DLB's heterogeneous nature, advocating for deeper exploration of its diverse pathological pathways, genetic predispositions, and clinical profiles to improve diagnosis and treatment outcomes. Understanding this heterogeneity is crucial for the development of personalized therapeutic strategies and effective management of the disease. Show less