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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.To assess cognitive deficits in individuals with HD, particularly in individuals with PreHD, using an easily administered, brief but comprehensive, neuropsychological test.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.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.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.

IntroductionMeasuring Huntingtin (Htt) protein in peripheral cells represents an essential step in biomarker discovery for Huntington’s Disease (HD), however to date, investigations into the salivary expression of Htt has been lacking.MethodIn the current study, we quantified total Htt (tHtt) and mutant Htt (mHtt) protein in matched blood and saliva samples using single molecule counting (SMC) immunoassays: 2B7-D7F7 (tHtt) and 2B7-MW1 (mHtt). Matched samples, and clinical data, were collected from 95 subjects: n=19 manifest HD, n=34 premanifest HD (PM), and n=42 normal controls (NC). ResultsTotal Htt and mHtt levels were not correlated in blood and saliva. Plasma tHtt was significantly associated with age, and participant sex; whereas salivary mHtt was significantly correlated with age, CAG repeat length and CAP score. Plasma and salivary tHtt did not differ across cohorts. Salivary and plasma mHtt were significantly increased in PM compared to NC; salivary mHtt was also significantly increased in HD compared to NC. Only salivary tHtt and mHtt were significantly correlated with clinical measures.Conclusions Salivary Htt is uniquely associated with clinical measures of HD and offers significant promise as a relevant, non-invasive HD biomarker. Its use could be immediately implemented into both translational and clinical research applications.

IntroductionThe inclusion of premanifest Huntington's Disease (Pre-HD) subjects in clinical trials necessitates selecting those who are near transition to manifest Huntington's disease (Man-HD). We previously determined that plasma neurofilament light (NfL) levels are significantly correlated with predicted years to Man-HD onset, using established formulae. Recently, a new normalized prognostic index (PIN) score for predicting Pre-HD disease progression has been validated. Our objective was to determine whether plasma NfL levels are similarly associated with PIN score and PIN score-derived years to Man-HD onset (PIN-YTO).Method112 individuals (46 Pre-HD, 66 Man-HD) underwent blood sample collection and clinical assessment, inclusive of the Symbol Digit Modalities Test and Unified Huntington's Disease Rating Scale Total Motor Score. Plasma NfL levels were measured using a Meso Scale Discovery assay.ResultsPre-HD and Man-HD cohorts differed by age (p10 predicted years from Man-HD onset, compared to those ≤10 predicted years.ConclusionsWe have extensively shown that plasma NfL levels are associated with predicted years to manifest HD onset in Pre-HD participants, and present a plasma NfL cut-point that may help exclude far-from-onset Pre-HD patients from clinical trials.

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