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Comparison of Cognitive and UHDRS Measures in Monitoring Disease

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Comparison of Cognitive and UHDRS Measures in Monitoring Disease Toh et al. Translational Neurodegeneration 2014, 3:15 http://www.translationalneurodegeneration.com/content/3/1/15 Translational Neurodegeneration RESEARCH Open Access Comparison of cognitive and UHDRS measures in monitoring disease progression in Huntington’s disease: a 12-month longitudinal study Eng A Toh1,2*, Michael R MacAskill1,2, John C Dalrymple-Alford1,2,3, Daniel J Myall2, Leslie Livingston1,2, Sandy AD Macleod4 and Tim J Anderson1,2,5 Abstract Progressive cognitive decline is a feature of Huntington’s disease (HD), an inherited neurodegenerative movement disorder. Comprehensive neuropsychological testing is the ‘gold standard’ to establish cognitive status but is often impractical in time-constrained clinics. The study evaluated the utility of brief cognitive tests (MMSE and MoCA), UHDRS measures and a comprehensive neuropsychological tests battery in monitoring short-term disease progression in HD. Twenty-two manifest HD patients and 22 matched controls were assessed at baseline and 12-month. A linear mixed-effect model showed that although the HD group had minimal change in overall global cognition after 12 months, they did show a significant decline relative to the control group. The controls exhibited a practice effect in most of the cognitive domain scores over time. Cognitive decline at 12-month in HD was found in the executive function domain but the effect of this on global cognitive score was masked by the improvement in their language domain score. The varying practice effects by cognitive domain with repeated testing indicates the importance of comparing HD patients to control group in research trials and that cognitive progression over 12 months in HD should not be judged by changes in global cognitive score. The three brief cognitive tests effectively described cognition of HD patients on cross-sectional analysis. The UHDRS cognitive component, which focuses on testing executive function and had low variance over time, is a more reliable brief substitute for comprehensive neuropsychological testing than MMSE and MoCA in monitoring cognitive changes in HD patients after 12 months. Keywords: Huntington’s disease, Disease progression, Cognition, UHDRS, Longitudinal Background for easily administered and yet robust tool to detect cogni- Huntington’s disease (HD) is an inherited neurodegener- tive changes in HD. Comprehensive neuropsychological ative disease caused by expansion of CAG trinucleotide testing is necessary to verify cognitive status. However, repeats secondary to mutation in the huntingtin gene on neuropsychological batteries are time-consuming and chromosome 4p16.3 [1]. The disease is characterized by brief cognitive screening tools such as the Mini Mental involuntary hyperkinetic movements, cognitive impair- State Examination (MMSE) and the Montreal Cognitive ment and behavioural disorders. Cognitive impairment, Assessment (MoCA) are commonly used in clinical set- which may be evident even in gene-positive individuals tings and in a broad range of conditions. The Unified yet to be clinically diagnosed [2-5], is progressive in nature Huntington’s Disease Rating Scale (UHDRS), a standard and a contributing factor in the loss of everyday function assessment tool for HD, also includes a brief cognitive [6]. Subtle cognitive impairment can be overlooked by cli- component. nicians during routine follow-up [7], indicating the need The MMSE [8] comprises eleven questions spanning five aspects of cognitive function: executive function, lan- guage, memory function, visuospatial ability and orienta- * Correspondence: [email protected] 1Department of Medicine, Christchurch School of Medicine & Health tion. It has good inter-rater, test and re-test reliability in Sciences, University of Otago, Christchurch, New Zealand differentiating cognitive status in dementia syndromes [9] 2 New Zealand Brain Research Institute, Christchurch, New Zealand and other disorders featuring cognitive impairment [10]. Full list of author information is available at the end of the article © 2014 Toh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Toh et al. Translational Neurodegeneration 2014, 3:15 Page 2 of 10 http://www.translationalneurodegeneration.com/content/3/1/15 Nevertheless, it is influenced by demographic factors such Table 1 Demographic characteristics (mean and SD) of as age, education and cultural background [9,11,12]. The control and HD groups MoCA places greater emphasis than the MMSE on nam- Mean (SD) ing, attention, abstraction and delayed recall, functions Control group HD group that are most likely to be compromised in the earlier n=22 n=22 stages of cognitive impairment and unlike the MMSE, it Age 50 (15) 50 (15) compensates for education level [13]. Both the MMSE CAG repeat no. - 44 (4) and MoCA have been employed as measures of cognitive Education level (years) 13 (2) 13 (2) performance in manifest HD patients [14-17] and MoCA Follow-up interval (weeks) 53 (3) 54 (4) was also found to have higher sensitivity without losing specificity than the MMSE in identifying those with cog- Retention rate at 12-month 91% (n = 20) 100% (n = 22) nitive impairment in HD [16]. Furthermore, Bezdicek et al. [17] demonstrated a strong correlation between English and consented to participate in compliance with the MoCA scores and comprehensive neuropsychological the requirements of the New Zealand Ministry of Health assessment scores in manifest HD patients. The UHDRS Ethics Committee. cognitive component [18] includes three tests of executive function – letter fluency test, Symbol Digit Modalities test Experiment procedure and Stroop test; which can be used with corrected norms The MMSE, MoCA and a comprehensive neuropsycho- to attenuate the impact of various demographic variables logical test battery were administered to all participants. [19,20]. The comprehensive assessment of cognitive function The progressive nature of HD means that any cog- used 19 neuropsychological tests to assess six domains nitive assessments should also be useful longitudinally. of cognitive function (executive function; working mem- HD patients are routinely followed up at clinics at 6- ory and attention; learning and memory; processing speed; month and 12-month intervals thus it is preferable that language; and visuospatial function). These tests were: ex- brief cognitive assessment tools are sensitive to changes ecutive function: letter, action and category fluency tests even over relatively short time intervals. Effective yet [21], Trail Making Test (Part B), Stroop-interference test; brief cognitive tools would enable easier detection of working memory and attention: digits forward, backward cognitive changes in HD patients in clinic settings than and sequencing tests [22], Symbol Digit Modalities Test time consuming comprehensive cognitive assessment [23] and Ruff 2 & 7 Cancellation Test – Accuracy [24]; and also assist health care providers in designing treat- learning and memory: Short California Verbal Learn- ment and care plans aimed at improving patient’s quality ing Test-II and Brief Visuospatial Memory Test-Revised; of life. MMSE and MoCA have been extensively evalu- processing speed: Stroop-word reading, Stroop-colour ated in previous cross-sectional HD studies [14-16] but naming, Trail Making Test (Part A) and Ruff 2 & 7 to our knowledge, there is no longitudinal data on the Cancellation Test – Speed; language: Brief Boston Naming utility of these brief cognitive tests compared to UHDRS Test [25] and Indiana University Token Test [26]; and cognitive assessment in monitoring cognitive changes in visuospatial function: Judgement of Line Orientation test HD patients. Therefore the objective of this study was to (Form H) and Rey Complex Figure Copying test. For the examine and compare the relative utility of two widely MMSE, both alternatives (‘World’ spelled backwards and used brief cognitive tests (MMSE and MoCA) concur- serial sevens) were assessed. The number of tests adminis- rently with the UHDRS cognitive assessment to a com- tered was evenly distributed over two separate sessions, prehensive neuropsychological test battery for monitoring one week apart and presented in the same order for all cognitive changes in HD patients over a short interval of participants. Each session began with the MMSE in the 12 months. Such a direct comparison has not been previ- first and MoCA in the second session. The three-part ously reported. UHDRS, comprising motor, cognitive and behavioural components, was administered in the first session to the Methods HD group only. All returning participants were reassessed Study participants were a convenience sample of 22 in identical manner 12 months later. manifest HD patients (10 males and 12 females) with mild to moderate disease severity and 22 age, gender Data analysis and education matched control volunteers recruited Cognitive status – normal, mild cognitive impairment through the New Zealand Brain Research Institute data- (MCI) or dementia – of HD participants was determined base (Table 1). Patients were genetically verified and clin- using evidence
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