Comparing phenotypic features between Parkinson’s disease dementia and dementia with Lewy bodies

Abstract Background Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are two synucleinopathies that share considerable overlap in their clinical and pathological characteristics. Objective This study aimed to evaluate the profile of phenotypic features across PDD and DLB to highlight their shared and distinctive features to explore any possible neurobiological underpinnings. Methods Patients diagnosed with Parkinson's disease dementia (PDD) (n=31) and dementia with Lewy bodies (DLB) (n=30) underwent evaluation for motor and non-motor symptoms using the International Parkinson and Movement Disorder Society -Unified Parkinson's Disease Rating Scale, the Scales for Outcomes in Parkinson’s Disease-Psychiatric Complications, the Montreal Cognitive Assessment, the Hospital Anxiety and Depression Scale and the Epworth Sleepiness Scale. Results Patients with PDD showed a more severe phenotype than those with DLB, with higher scores in motor severity, hallucinations, delusions, somnolence, and urinary dysfunction (all p≤0.01). The correlations between neuropsychiatric symptoms differed between groups. In both PDD and DLB, depression correlated with anxiety (PDD ρ=0.54; DLB ρ=0.65; both p<0.001). In PDD, depression was additionally correlated with delusions (ρ=0.47; p<0.001), apathy (ρ=0.41; p<0.001), and sexual preoccupation (ρ=0.35; p<0.001), whereas in DLB depression correlated with hallucinations (ρ=0.38; p<0.001). PDD patients showed greater impairment in activities of daily living (ADLs) than DLB patients (p<0.001), correlating with motor severity (ρ=0.65; p<0.001) and fatigue (ρ=0.58; p<0.001). In DLB, impaired ADLs were linked to hallucinations (ρ=0.39; p<0.05), poorer cognition (ρ=0.47; p<0.01), urinary dysfunction (ρ=0.38; p<0.001), and fatigue (ρ=0.45; p<0.001). Conclusion Despite being grouped under Lewy body dementias, these findings show PDD and DLB have distinct phenotypes reflecting their neurobiological underpinnings. This has implications for symptomatic and disease-modifying management. Future research should explore pathological mechanisms of these characteristics to improve diagnosis and treatment strategies.