Clinical severity of Huntington's disease does not always correlate with neuropathologic stage.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a triplet-repeat, CAG expansion mutation. Although CAG repeat length is thought to correlate with pathologic burden and disease severity, considerable variability in clinical phenotype remains. This study examined whether neuropathologic burden at autopsy corresponded with severity of clinical phenotype in HD. The brains of 24 patients with a clinical and genetic diagnosis of HD were analyzed at autopsy. Subjects were stratified on the basis of Vonsattel staging as mild/moderate (stage 1-2; n = 7) or severe (stage 3-4; n = 17). Clinical severity was assessed on the basis of the Mini-Mental State Examination (MMSE; 0-30) and two Unified Huntington's Disease Rating Scale (UHDRS) functional components: the Independence Scale (10-100) and the Total Functional Capacity (0-13). Mild/moderate subjects were significantly older, had lower CAG repeat lengths, and greater fixed brain weights than those classified as severe. Patients who were pathologically classified as severe at autopsy were, on average, younger at age of onset and death and less well educated. Despite obvious clinical and pathological differences between mild-moderate and severe HD subjects at autopsy, mean MMSE scores of the two groups before death were surprisingly similar. Correlations between Vonsattel stage and functional assessment scores before death were low and not statistically significant. Our results suggest that the extent of striatal changes in HD may not always correlate with clinical disease severity as measured by UHDRS functional scales.

A comparison of two brief screening measures of cognitive impairment in Huntington's disease.

The goal of this study was to explore whether the Montreal Cognitive Assessment (MoCA), a new screening instrument, would be more sensitive to mild to moderate cognitive impairment in Huntington's disease (HD) than an established screening measure, the Mini Mental State Exam (MMSE). Our reasoning for this query is that the MoCA includes a broader range of test items and an additional assessment of executive functioning and attention compared with the MMSE. Using the receiver operating characteristic (ROC) analysis to examine performance of HD and control groups on both tests on overall scores and scores from various subdomains (i.e., visuospatial abilities) revealed that the MoCA achieved higher sensitivity without sacrificing specificity in many domains relative to the MMSE.

Cognitive and functional decline in Huntington's disease: dementia criteria revisited.

The importance of designating criteria for diagnosing dementia lies in its implications for clinical treatment, research, caregiving, and decision-making. Dementia diagnosis in Huntington's disease (HD) is often based on criteria developed for Alzheimer's disease requiring memory loss. However, it is likely that other cognitive deficits contribute to functional impairment in HD before memory declines. The goal is to identify cognitive deficits that contribute to functional impairment to support dementia criteria that reflect HD neuropathology. Eighty-four HD mutation-positive subjects completed neuropsychological tests and the Unified Huntington's Disease Rating Scale Functional Independence Scale (FIS). Functional impairment was defined as 80 or below on the FIS. Speed of processing, initiation, and attention measures accounted for 70.0% of the variance in FIS ratings (linear regression) and correctly classified 91.7% of subjects as functionally impaired or intact (logistic regression). Measures of memory, motor impairment except dysarthria, neuroleptic use, and depressed mood did not improve prediction. A definition of HD dementia that includes cognitive impairment in at least two areas of cognition but does not require a memory deficit, in the context of impaired functional abilities and a deteriorating course, more accurately reflects HD neuropathology and could lead to improved research methods and patient care.

Difficulty modifying a sustained motor response in prodromal Huntington's disease.

We investigated the nature of motor symptoms in the preclinical stage of Huntington's disease. Individuals with the CAG expanded repeat of Huntington's disease (prHD) and two control groups were tested on a task requiring a releasing movement (releasing a depressed button) followed by a ballistic movement (pressing a different button). Movement times were measured separately for releasing and ballistic movements. The mean reaction time of the prHD group was significantly longer when releasing a movement than that of the other groups. The groups, however, did not differ significantly on movement time for ballistic movements. Our results show that motor slowing is evident prior to the clinical diagnosis of Huntington's disease and may reflect difficulty in modifying a sustained motor program.