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PROGRESSIVE COGNITIVE DIFFICULTIES IN ADULT PATIENTS WITH MITOCHONDRIAL DISEASE
  1. Heather Moore,
  2. Thomas Kelly,
  3. Michael Trenell,
  4. Ian Deary,
  5. Douglass Turnbull,
  6. Grainne Gorman
  1. Newcastle University; Edinburgh University

    Abstract

    Introduction Mitochondrial diseases are a common group of genetic neurometabolic disorders characterised by heterogeneous clinical features including myopathy, auditory, visual, cardiac, and brain dysfunction. Mitochondrial dysfunction has been implicated in ageing as well as in a number of other neurodegenerative diseases. Thus, information gained from research in patients with mitochondrial disease may provide useful insights into other age–related and neurodegenerative diseases. Cognitive features are present in patients with mitochondrial disease, but have not been comprehensively explored.

    Aims This longitudinal study sought to compare estimated premorbid and current levels of general cognitive functioning and examine the cognitive profile of patients with mitochondrial disease.

    Methods Forty–nine adult patients harbouring either the m.3243A>G or m.8344A>G mtDNA point mutations and 49 age–and ability–matched controls were recruited. The Wechsler Test of Adult Reading (WTAR) was performed to estimate premorbid cognitive ability and the Wechsler Adult Intelligence Scale–IV (WAIS–IV) was used to assess current cognitive functioning. The Speed of Comprehension test and the Birt Memory & Information Processing Battery were employed to assess processing speed in addition to WAIS–IV tests. The Wechsler Memory Scale–IV (WMS–IV) was used to measure auditory memory. The Tower test, Verbal Fluency (phonetic and semantic), and the Self–Ordered Pointing task were employed to measure executive functions. The Addenbrooke's Cognitive Examination–Revised (ACE–R) provided a clinical screening tool for cognitive impairment. Baseline, cross–sectional data of patients with mitochondrial disease are considered here. Results: Patients with mitochondrial disease performed significantly worse than the norm on the WTAR (p=.002), suggestive of developmental cognitive problems. Current cognitive functioning, measured by the WAIS–IV, was also significantly lower than the norm (p<.001), with 22% of patients scoring more than 2SD below the norm. There was a significant decline in cognitive ability between premorbid estimates (WTAR) and current levels of cognitive ability (WAIS–IV; mean change:–8.37 IQ points; p<.001). Comparing the WAIS–IV Index scores from four different areas of cognitive functioning, patients with mitochondrial disease performed significantly better on Perceptual Reasoning than Processing Speed (p=.008), equivalent to an average difference of 7 IQ points. Logical memory was impaired in this group compared to the norm (Immediate: p<.001, Delayed: p<.001), whereas verbal declarative memory was not. Both Verbal Fluency and Tower Tests showed evidence of executive dysfunction.

    Conclusion These findings demonstrate widespread cognitive difficulties that can undermine independence and quality of life in patients with mitochondrial disease, and emphasise the need to incorporate cognitive testing into clinical practice, in order to ensure that appropriate care is provided. These findings serve as an informative guide for assessing the true nature and severity of cognitive disability in patients with mitochondrial disease and preface future studies assessing speed of progression and final cognitive outcome, whilst providing clues to the role of mitochondrial dysfunction in other neurodegenerative conditions and age–related cognitive decline.

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