Initial neuropsychological impairments in patients with the E46K mutation of the α-synuclein gene (PARK 1)

Abstract

Introduction: In 2004 we described the mutation E46K of the α-Synuclein (SNCA). These patients show Parkinson's disease with early cognitive impairment, sleep disorders and autonomic dysfunction.

Objective: The main objective is to identify early neuropsychological impairments in patients with the E46K mutation.

Methods: This is a longitudinal neuropsychological study of 4 of the 5 surviving patients with E46K mutation by semi-structured interviews and the following scales: Mattis Dementia Rating Scale (MDRS), semantic and phonemic verbal fluency tests (VFT), Benton Visual Retention Test (BVRT), Stroop Test (STROOP), Clock drawing test (CLOCK), WAIS III Letter and Number sequencing (WAIS III LN), Rey Auditory Verbal Learning Test (RAVLT) and Benton Judgement of Line Orientation Test (BJLOT). Motor status was assessed by UPDRS III.

Results: Motor status: Patients 1, 2 and 3 present mild to moderate Parkinson disease of 7, 8 and 3years of evolution respectively, patient 4 is asymptomatic. Cognitive status: Patient 2 and 3 both refer cognitive decline while patient 1 presents no cognitive complaints, however they all show a progressive cognitive decline across various tasks. Tests of frontal function showed the first alterations in all patients but fluctuate. The first cognitive complaints coincide with deterioration of tasks of posterior cortical basis. Patient 4 presents a normal performance on all tests. Patient 1, 2 and 3 have all presented visual hallucinations.

Conclusions: A fluctuating frontal impairment is observed at early stages. Prominent visuospatial alterations and visual hallucinations suggest that posterior cortical dysfunction might be a distinct early feature of the cognitive impairment observed in patients with this mutation.