Abstract
ObjectiveTo determine the cognitive profile of adult patients with mitochondrial disease, and the effect of disease severity on cognition.MethodsUsing a prospective case‐control design, we compared cognition of patients to normative data and to matched controls, assessed three times over 18 months. Forty‐nine patients with m.3243A>G (N = 36) and m.8344A>G (N = 13) mtDNA mutations and 32 controls, matched by age (±5 years) and premorbid cognition (±10 WTAR FSIQ points), participated. Participants completed neuropsychological assessments of general cognition (WAIS‐IV), executive function (D‐KEFS), and memory (WMS‐IV). Potential predictors of cognition were explored.ResultsPatients show mild‐to‐moderate premorbid cognitive impairment, but substantial impairment in current general cognition and distinct domains, including verbal comprehension, perceptual reasoning, working memory, processing speed, and memory retrieval. Executive dysfunction may be caused by slower decision‐making. Patients performed worse than controls, except on memory tasks, indicating intact memory, when premorbid cognition is controlled for. Premorbid cognition and disease severity were consistent predictors of cognition in patients; however, cognitive decline appears slow and is unlikely in the short‐term, when other disease‐specific factors remain stable.InterpretationPatients should be monitored to facilitate early identification of a complex profile of cognitive deficits and individuals with higher disease burden should be followed up more closely. On development of cognitive difficulties, appropriate compensatory strategies should be determined through in‐depth assessment. Using strategies such as slower presentation of information, multiple modes of presentation, active discussion to aid understanding and decision‐making, and use of memory aids, may ameliorate difficulties.
Highlights
Mitochondrial diseases are a common group of genetic neuromuscular disorders characterized by genotypic and phenotypic heterogeneity with a prevalence comparable to many other genetically determined neurodegenerative diseases.[1]
In patients with mitochondrial disease, high rates of cognitive delay, cognitive and memory impairment, and dementia have been reported in small case studies and review articles only
Forty-nine adult patients with mitochondrial disease, with either m.3243A>G (N = 36) or m.8344A>G (N = 13)–related mitochondrial disease, and 32 controls matched for age (Æ5 years) and premorbid cognitive ability (Æ10 Wechsler Test of Adult Reading[15] (WTAR) FSIQ points) participated
Summary
Mitochondrial diseases are a common group of genetic neuromuscular disorders characterized by genotypic and phenotypic heterogeneity with a prevalence comparable to many other genetically determined neurodegenerative diseases.[1]. In patients with mitochondrial disease, high rates of cognitive delay, cognitive and memory impairment, and dementia have been reported in small case studies and review articles only. These studies are primarily a retrospective analysis of patients manifesting high genotypic variability and disease burden. Focal cognitive deficits of memory, executive functioning, visuospatial abilities, and processing speed have been reported in small-scale, systematic investigations carried out at a single time point, with marked variability in results.[2,3,4,5,6,7,8,9,10,11] While studies have suggested mtDNA genotype-specific differences in cognition[6]; group sizes have been insufficient to identify specific profiles and cognitive performance may better relate to disease burden.[11]. We sought to evaluate cognitive ability and delineate potential predictors of cognition in patients with the m.3243A>G and m.8344A>G-related mitochondrial diseases[1] compared to standardized normative data[12,13,14] and to age- and premorbid cognitive ability-matched control participants over time
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