The Repeatable Battery for the Assessment of Neuropsychological Status, While Useful for Measuring Cognitive Changes in Manifest Huntington Disease, May Show Limited Utility in Premanifest Disease.

BACKGROUND: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a brief, standardized neuropsychological test that assesses several areas of cognitive function. Recent studies, although sparse, have examined the use of the RBANS to detect cognitive deficits in individuals with manifest Huntington disease (HD); however, no studies have investigated its utility to detect cognitive deficits in individuals with premanifest HD (PreHD), where cognitive symptoms are thought to be more subtle. OBJECTIVE: To assess cognitive deficits in individuals with HD, particularly in individuals with PreHD, using an easily administered, brief but comprehensive, neuropsychological test. METHOD: We administered the RBANS to 31 individuals with HD, 29 individuals with PreHD, and 22 healthy controls (HC) at an academic HD clinical research center and collected RBANS Total, Index, and subtest scores for group comparisons. RESULTS: The HD group had significantly lower RBANS Total, Index, and subtest scores than the HC. The PreHD group had significantly lower RBANS Total scores and Coding subtest scores than the HC, but no other significant group differences were identified. CONCLUSION: Our results substantiate previous findings of significant impairment on the RBANS in individuals with HD. In addition, we are the first to demonstrate that, although the RBANS can identify deficits in psychomotor speed and information processing in individuals with PreHD, it does not appear to have the ability to detect impairment in any additional cognitive domains in individuals with PreHD.

Plasma neurofilament light in Huntington's disease: A marker for disease onset, but not symptom progression.

OBJECTIVE: To investigate whether plasma NfL levels correlate with clinical symptom severity in premanifest (PM) and manifest HD (HD) individuals, and whether a NfL cut-point could distinguish PM from HD patients with reasonable accuracy. METHOD: 98 participants (33 control, 26 PM, 39 HD), underwent blood sample collection and clinical assessment, using both UHDRS and non-UHDRS measures, at one academic HD Center. Years to onset (YTO), probability of disease onset in 5 years, and predicted years until 60% onset probability were also calculated. NfL levels were measured using a Meso Scale Discovery assay. RESULTS: Cohorts differed by age. NfL levels differed significantly across diagnostic groups and were significantly correlated with age. Age-adjusted NfL levels were not correlated with clinical measures in either HD or PM cohorts, but were correlated when cohorts were combined. In PM subjects, NfL levels correlated with YTO, probability of onset in 5 years, and years until 60% onset probability. Using ROC analysis, a NfL cut-point of <53.15 pg/ml distinguished HD from control; <74.84 pg/ml distinguished HD from PM. CONCLUSIONS: These findings implicate plasma NfL as a peripheral prognostic marker for premanifest-HD. Notably, we show that significant correlations between NfL and clinical symptoms are detected only when PM + HD subjects are combined, but not within HD subjects alone. To date, prior studies have investigated the clinical usefulness of NfL exclusively in merged PM + HD cohorts. Our data suggests a biasing of these previous correlations, and hence potentially limited usefulness of plasma NfL in monitoring HD symptom progression, for example, in clinical trials.

Central Cognitive Processing Speed Is an Early Marker of Huntington's Disease Onset.

BACKGROUND: Several studies have suggested that cognitive processing speed may be useful for assessing early cognitive change in premanifest Huntington's disease (HD); however, current measures lack the ability to control for the effects of motor dysfunction commonly found in HD. The Computerized Test of Information Processing (CTiP) is a rapidly administered computerized tool that allows for the examination of central cognitive processing speed by using motor-corrected scores to account for motor dysfunction. OBJECTIVE: To examine central cognitive processing speed as an early marker of HD onset using the CTiP. METHODS: The CTiP and other measures were administered to 102 HD gene carriers and 55 healthy adults (HA). Gene carriers included presymptomatic HD (pre-HD; n = 33), prodromal HD (pro-HD; ie, individuals close to disease onset; n = 23), and mild-moderate HD (HD; n = 46). RESULTS: The HD group performed significantly slower than all other groups (HA, pre-HD, and pro-HD) on most subtests (Ps < .05). Moreover, the pro-HD group performed significantly slower than the HA group on both motor-corrected subtests (Ps < 0.05). Effect sizes associated with significant group differences between the pro-HD and HA groups on motor-corrected CTiP subtests (d = 0.73 and 0.84) were similar to effect sizes associated with group differences on the Symbol Digit Modalities Test (d = .82) and other traditional cognitive assessments (Montreal Cognitive Assessment, d = .75; Mini-Mental State Examination, d = .84). CONCLUSIONS: The CTiP may be a useful marker of deficits in central cognitive processing speed in individuals close to manifest onset of HD.