Selective cognitive impairment and hyposmia in p.A53T SNCA PD vs typical PD

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ObjectiveTo evaluate nonmotor symptoms in early SNCA/p.A53T Parkinson disease (PD) (A53T PD) compared to typical PD (tPD).MethodsThe presence of hyposmia, neuropsychiatric, dysautonomic, and sleep disturbances was assessed by standardized questionnaires and validated scales in 18 patients with A53T PD and 18 patients with tPD, matched for age, sex, and disease duration. All patients were enrolled into the Parkinson's Progression Markers Initiative study.ResultsThe levodopa equivalent daily dose was higher in the A53T PD (p = 0.018) group vs the tPD group. Scores on the University of Pennsylvania Smell Identification Test (p = 0.001), Benton Judgement of Line Orientation test (p = 0.001), Letter Number Sequencing Test (p = 0.002), and phonemic verbal fluency (p = 0.002) were lower in the A53T PD group vs the tPD group. In contrast, overall cognition, verbal memory, and semantic fluency were similar between groups.ConclusionThe observed selective cognitive impairment reflecting frontal-parietal network dysfunction, together with impaired olfaction, define a set of nonmotor dysfunctions related to A53T PD. These results have implications for the prognosis of patients with A53T PD. Moreover, as the archetypal α-synucleinopathy, such results may give insights into tPD.

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