Establishing normative data for the evaluation of cognitive performance in Huntington's disease considering the impact of gender, age, language, and education.

BACKGROUND: A declining cognitive performance is a hallmark of Huntington's disease (HD). The neuropsychological battery of the Unified HD Rating Scale (UHDRS'99) is commonly used for assessing cognition. However, there is a need to identify and minimize the impact of confounding factors, such as language, gender, age, and education level on cognitive decline. OBJECTIVES: Aim is to provide appropriate, normative data to allow clinicians to identify disease-associated cognitive decline in diverse HD populations by compensating for the impact of confounding factors METHODS: Sample data, N = 3267 (60.5% females; mean age of 46.9 years (SD = 14.61, range 18-86) of healthy controls were used to create a normative dataset. For each neuropsychological test, a Bayesian generalized additive model with age, education, gender, and language as predictors was constructed to appropriately stratify the normative dataset. RESULTS: With advancing age, there was a non-linear decline in cognitive performance. In addition, performance was dependent on educational levels and language in all tests. Gender had a more limited impact. Standardized scores have been calculated to ease the interpretation of an individual's test outcome. A web-based online tool has been created to provide free access to normative data. CONCLUSION: For defined neuropsychological tests, the impact of gender, age, education, and language as factors confounding disease-associated cognitive decline can be minimized at the level of a single patient examination.

Validation Study of a German Cognitive Battery for Huntington's Disease: Relationship Between Cognitive Performance, Functional Decline, and Disease Burden.

OBJECTIVE: Cognitive decline is a key characteristic of Huntington's disease (HD). This study aimed to investigate the diagnostic accuracy of a cognitive battery with six tests used by most HD research centers to assess cognitive impairment in HD. METHOD: In total, 106 HD patients in different disease stages with more (HD-CD, N = 30) and less cognitive impairments (HD-NC, N = 70) and 100 healthy controls (NC) were matched by age, sex, and education and were examined using a standardized protocol including cognitive, motor, and functional assessments. RESULTS: One-way between-groups analysis of variance showed that controls performed significantly better than HD patients and that HD-NC significantly outperformed HD-CD patients in all cognitive tests (NC > HD-NC > HD-CD), with all Games-Howell post-hoc tests p < .001. Analyses using area under the receiver-operating characteristic curve (AUC) disclosed the diagnostic accuracy of all tests included in the battery to discriminate between NC and HD patients with AUC ranging from 0.809 to 0.862 (all p < .001) and between HD-CD and HD-NC patients with AUC ranging from 0.833 to 0.899 (all p < .001). In both analysis, Stroop Color Naming Test showed the highest discriminative potential. Additional analyses showed that cognitive deficits in all domains progressed with disease duration. Moreover, cognitive performance correlated with the severity of motor and functional impairment (all p < .001) and with the Disease Burden Score regardless of disease duration and age. CONCLUSION: Our results indicate that the cognitive battery is a suitable tool for assessing cognitive impairment in HD.

The relationship between impairment of voluntary movements and cognitive impairment in Huntington's disease.

The relationship between motor symptoms and cognitive impairment in Huntington's disease (HD) is still discussed. We analysed 45 HD patients in various stages using Unified Huntington's Disease Rating Scale motor subscale (voluntary and involuntary components were evaluated separately), verbal memory and executive functions tests. Partial correlations controlling for HD duration and age were used to estimate the relationships among factor scores for motor and cognitive impairment. Voluntary components of motor performance were found to be significantly correlated with verbal short-term memory disturbances (r = -0.361, P = 0.03), with tests of executive functions more dependent on motor performance (r = 0.640, P < 0.01) and also with tests of executive functions less dependent on motor performance (r = 0.461, P < 0.01). Involuntary components did not correlate significantly with any part of cognitive performance.

Variation of selective gray and white matter atrophy in Huntington's disease.

The relationship between the extent of local gray/white matter atrophy, genetic load, and clinical impairment was studied in Huntington's disease (HD) by means of voxel-based morphometry. T1-weighted brain images from 33 patients (mean age 49.5, range 25-73 years) with HD duration of 1 to 15 years were analyzed by correlation of each voxel intensity with the number of CAG triplets and the UHDRS-motor score (P < 0.001). The CAG number correlated inversely with gray matter intensity in the caudate nuclei and with white matter intensity in the both postcentral gyri and the right cerebellum. The UHDRS-motor score correlated inversely with the atrophy of both caudates, right hippocampus, calcarine fissure, and with the white matter along the fourth and lateral ventricles. While atrophy of the caudate nucleus was related to a higher number of CAG triplets and higher UHDRS-motor score, atrophy in other parts of the brain covaried with the two parameters differently: higher genetic load was associated with greater loss of cortical somatosensory projections and the worse UHDRS-motor score was accompanied by increased atrophy of the internal capsule, lower brainstem, hippocampus, and visual cortex. According to our results, the genetic load in HD predicts partially the extent of selective gray/white brain matter atrophy, which is then reflected in the severity of motor impairment.

Unified Huntington's disease rating scale: clinical practice and a critical approach.

The purpose of this study was to test the usefulness of the Unified Huntington's Disease Rating Scale (UHDRS) in clinical practice. The UHDRS was used to examine 45 persons with genetically diagnosed Huntington's disease (HD) in various stages. The rate of motor involvement, cognitive deficit and reliance on nursing care rose in linear proportion to HD duration. The severity of motor involvement correlated significantly with all UHDRS subscales except for that of behavioral disorders, the rate of these disorders being unrelated to any of the parameters under study. The number of CAG triplets was inversely correlated with the age at onset of HD. Being considerably time consuming, administration of the whole UHDRS calls for interdisciplinary co-operation. For valid data acquisition, the participation of caregivers is also essential. In clinical practice it is advisable regularly to monitor the patient's conditions and the efficacy of treatment using the UHDRS motor, functional and behavioral subscales. Cognitive tests present difficulties but, in view of the progressive cognitive deterioration in HD, they are very useful in the early stage of the disease. The UHDRS does not assess impaired voluntary motor activity, or furnish information relating to therapy, dysphagia, weight loss, sexual problems or drug abuse.