Objective: The alpha-synuclein gene (SNCA) is implicated in both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The purpose of this case study was to describe the neuropsychological profile, clinical trajectory, and treatment course of an individual with a known SNCA gene duplication who was followed over the course of three years. Methods: The patient was a healthy man who developed olfactory changes in early adulthood followed by parkinsonism and cognitive concerns around age 40. He underwent serial neurologic and neuropsychological evaluations and neuroimaging, as well as genetic testing for PD gene mutations. He consented to share his medical information to increase awareness of his condition. Results: Initial neuropsychological evaluation (age 44) revealed mild cognitive impairment primarily affecting executive and frontal/subcortical functions. Follow-up evaluations showed rapid cognitive decline that far surpassed the patient's Parkinsonism, which responded well to carbidopa-levodopa. As symptoms progressed, he also developed features characteristic of DLB, including cognitive fluctuations, rapid eye movement sleep behavior disorder, and visual hallucinations. Conclusion: SNCA gene duplication has classically been associated with a slowly progressive syndrome closely resembling idiopathic PD, but less frequently it can cause rapidly progressive dementia. This case study is the first to describe this rare phenotype in terms of its full neuropsychological profile and trajectory. The case highlights the value of a transdisciplinary evaluation and treatment and brings up important ethical and practical issues that should be considered when working with patients who have suspected or known genetic disorders.
Keywords: PARK4; Parkinsonism; Parkinson’s disease; SNCA; alpha-synuclein; differential diagnosis; early-onset dementia.