Neuropsychological Functioning in Primary Dystonia: Updated and Expanded Multidomain Meta‐Analysis

Abstract

A BS TRACT: Background: Primary dystonia is conventionally considered as a motor disorder, though an emerging literature reports associated cognitive dysfunction.Objectives: Here, we conducted meta-analyses on studies comparing clinical measures of cognition in persons with primary dystonia and healthy controls (HCs). Methods: We searched PubMed, Embase, Cochrane Library, Scopus, and PsycINFO (January 2000-October 2020). Analyses were modeled under random effects. We used Hedge's g as a bias-corrected estimate of effect size, where negative values indicate lower performance in dystonia versus controls. Between-study heterogeneity and bias were primarily assessed with Cochran's Q, I 2 , and Egger's regression. Results: From 866 initial results, 20 studies met criteria for analysis (dystonia n = 739, controls n = 643; 254 effect sizes extracted). Meta-analysis showed a significant combined effect size of primary dystonia across all studies (g = À0.56, P < 0.001), with low heterogeneity (Q = 25.26, P = 0.15, I 2 = 24.78). Within-domain effects of primary dystonia were motor speed = À0.84, nonmotor speed = À0.83, global cognition = À0.65, language = À0.54, executive functioning = À0.53, learning/memory = À0.46, visuospatial/construction = À0.44, and simple/complex attention = À0.37 (P-values <0.01). High heterogeneity was observed in the motor/nonmotor speed and learning/memory domains. There was no evidence of publication bias. Moderator analyses were mostly negative but possibly underpowered. Blepharospasm samples showed worse performance than other focal/cervical dystonias. Those with inherited (ie, genetic) disease etiology demonstrated worse performance than acquired. Conclusions: Dystonia patients consistently demonstrated lower performances on neuropsychological tests versus HCs. Effect sizes were generally moderate in strength, clustering around À0.50 SD units. Within the speed domain, results suggested cognitive slowing beyond effects from motor symptoms. Overall, findings indicate dystonia patients experience multidomain cognitive difficulties, as detected by neuropsychological tests.

Cognitive impairment in Chinese patients with cervical dystonia

“…Similarly, patients with CD were reported to have altered functional activity in the dorso-lateral-prefrontal loop, which may be involved in attention impairment (42,43). Moreover, several studies have reported language function impairment in CD and other types of focal dystonia like blepharospasm (44)(45)(46), which may indicate a connectivity dysfunction between the basal ganglia and the precuneus, thalamus, and frontal areas (44).…”

“…Others argued that CD may be a complex syndrome affecting multiple brain regions which are responsible for CI and other non-motor symptoms rather than a "pure" motor disorder (10,12,15). A recent meta-analysis failed to conclude the association between CI and other factors in CD owing to the small sample size and high heterogeneity of results (45). Yet, in our study, CI in patients with CD was highly associated with more severe motor symptoms, and this association was still valid between CD-RMCI and CD-RSCI in the subgroup analysis.…”

“…To conclude, the association between motor severity and CI indicates that there may be more widespread alterations beyond the basal ganglia, possibly including the frontal/prefrontal cortex and the cerebellum, which contribute to the pathophysiology of both motor symptoms and CI in patients with CD (42). The motor and non-motor regions may interact with each other during the development of the disease, resulting in different extents of motor impairment and CI (45). Future studies are needed to clarify the underlying mechanisms of the association between motor severity and CI.…”

“…This hypothesis would counter the commonly accepted view that CD is not a progressive disorder. However, a recent meta-analysis failed to detect the association between CI and disease duration in CD because of the small sample size and high heterogeneity of results (45). Therefore, longitudinal observations of cognition status in CD patients with large sample sizes are required in future prospective studies.…”

Topological differences and confounders of mental rotation in cervical dystonia and blepharospasm

“…In the same vein, temporal discrimination tasks for visual/tactile 59 and somatosensory 60 stimuli revealed significant impairment in CD and BS patients compared to HC, but no differences between the two focal dystonia groups. Beyond that, visuomotor and visuospatial ability is supposed to be disturbed in BS as well as in CD 61,62 . Therefore, despite the clearly diverging phenotypes of focal dystonia, neuropsychological performance seems to be similar in CD and BS, suggesting those findings as a common endophenotype.…”