Cognitive impairment in rapid‐onset dystonia‐parkinsonism

Abstract

Background Rapid-Onset Dystonia-Parkinsonism (RDP) is caused by mutations in the ATP1A3 gene. This observational study sought to determine if cognitive performance is decreased in patients with RDP compared with mutation-negative controls. Methods We studied 22 familial RDP patients, 3 non-motor manifesting mutation-positive family members, 29 mutation-negative family member controls in 9 families, and 4 unrelated RDP patients, totaling 58 individuals. We administered a movement disorder assessment, including the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Unified Parkinson’s Disease Rating Scale (UPDRS), and a cognitive battery of learning, memory, psychomotor speed, attention, and executive function. The cognitive battery was designed to evaluate a wide range of functions; recognition memory instruments were selected to be relatively pure measures of delayed memory, devoid of significant motor or vocal production limitations. Comparisons of standardized cognitive scores were assessed both with and without controlling for psychomotor speed, and similarly for severity of depressive symptoms. Results Among RDP patients, a majority had onset of motor symptoms by age 25, and had initial symptom presentation in the upper body (face, mouth, or arm). Among patients, the BFMDRS (mean ± SD, 52.1 ± 29.5) and UPDRS motor subscore (29.8 ± 12.7) confirmed dystonia-parkinsonism. The affected RDP patients performed more poorly, on average, than mutation-negative controls for all learning, memory, psychomotor speed, attention, and executive function scores (all P ≤0.01). These differences persisted after controlling for psychomotor speed and severity of depressive symptoms. Conclusions Impaired cognitive function may be a manifestation of ATP1A3 mutation and RDP.

Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

“…Similarly, a recent care report showed that 90% of RDP patients with onset at or after 18 years had trouble learning in school33. The α 3 +/D801Y mice were tested for spatial learning and memory performance using the Barnes Maze (Hippocampus-based spatial reference memory) and passive avoidance (amygdala- and hippocampus-based memory)34.…”

The Expanding Spectrum of Neurological Phenotypes in Children With ATP1A3 Mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and Beyond

“…33 A separate study with 29 patients with RDP showed consistent impairment in attention, verbal fluency, coding tasks, visual memory, and verbal learning tasks compared with controls, suggesting cognitive impairment as part of the RDP phenotype. 34 Published studies to date assessing detailed cognitive function in AHC are limited, but cognitive impairment is virtually universal among cohorts.…”

Altered Glutamate Protein Co-Expression Network Topology Linked to Spine Loss in the Auditory Cortex of Schizophrenia

“…The onset of RDP bears some similarities to that of first psychotic episodes in SCZ, including precipitation by an acute or sub-acute stressful event, sub-acute onset, and highest incidence of onset in the second decade of life(74). RDP patients with ATP1A3 mutations also display significant impairments in memory, attention, and executive function(75). 19% of RDP patients with an ATP1A3 mutation exhibited a psychotic syndrome characterized by auditory hallucinations(74), which occurred prior to or at onset of the motor symptoms.…”