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

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.