Validation of alternative dot counting test E-score cutoffs based on degree of cognitive impairment in veteran and civilian clinical samples.

OBJECTIVE: This study examined Dot Counting Test (DCT) performance among patient populations with no/minimal impairment and mild impairment in an attempt to cross-validate a more parsimonious interpretative strategy and to derive optimal E-Score cutoffs. METHOD: Participants included clinically-referred patients from VA (n = 101) and academic medical center (AMC, n = 183) settings. Patients were separated by validity status (valid/invalid), and subsequently two comparison groups were formed from each sample's valid group. Namely, Group 1 included patients with no to minimal cognitive impairment, and Group 2 included those with mild neurocognitive disorder. Analysis of variance tested for differences between rounded and unrounded DCT E-Scores across both comparison groups and the invalid group. Receiver operating characteristic curve analyses identified optimal validity cut-scores for each sample and stratified by comparison groups. RESULTS: In the VA sample, cut scores of ≥13 (rounded) and ≥12.58 (unrounded) differentiated Group 1 from the invalid performers (87% sensitivity/88% specificity), and cut scores of ≥17 (rounded; 58% sensitivity/90% specificity) and ≥16.49 (unrounded; 61% sensitivity/90% specificity) differentiated Group 2 from the invalid group. Similarly, in the AMC group, a cut score of ≥13 (rounded and unrounded; 75% sensitivity/90% specificity) differentiated Group 1 from the invalid group, whereas cut scores of ≥18 (rounded; 43% sensitivity/94% specificity) and ≥16.94 (unrounded; 46% sensitivity/90% specificity) differentiated Group 2 from the invalid performers. CONCLUSIONS: Different cut scores were indicated based on degree of cognitive impairment, and provide proof-of-concept for a more parsimonious interpretative paradigm than using individual cut scores derived for specific diagnostic groups.

Comparing the Independent and Aggregated Accuracy of Trial 1 and the First 10 TOMM Items for Detecting Invalid Neuropsychological Test Performance Across Civilian and Veteran Clinical Samples.

Previous studies support using two abbreviated tests of the Test of Memory Malingering (TOMM), including (a) Trial 1 (T1) and (b) the number of errors on the first 10 items of T1 (T1e10), as performance validity tests (PVTs). In this study, we examined the independent and aggregated predictive utility of TOMM T1 and T1e10 for identifying invalid neuropsychological test performance across two clinical samples. We employed cross-sectional research to examine two independent and demographically diverse mixed samples of military veterans and civilians (VA = 108; academic medical center = 234) of patients who underwent neuropsychological evaluations. We determined validity groups by patient performance on four independent criterion PVTs. We established concordances between passing/failing the TOMM T1e10 and T1, followed by logistic regression to determine individual and aggregated accuracy of T1e10 and T1 for predicting validity group membership. Concordance between passing T1e10 and T1 was high, as was overall validity (87-98%) across samples. By contrast, T1e10 failure was more highly concordant with T1 failure (69-77%) than with overall invalidity status (59-60%) per criterion PVTs, whereas T1 failure was more highly concordant with invalidity status (72-88%) per criterion PVTs. Logistic regression analyses demonstrated similar results, with T1 accounting for more variance than T1e10. However, combining T1e10 and T1 accounted for the most variance of any model, with T1e10 and T1 each emerging as significant predictors. TOMM T1 and, to a lesser extent, T1e10 were significant predictors of independent criterion-derived validity status across two distinct clinical samples, but they did not offer improved classification accuracy when aggregated.

Assessment of differential neurocognitive performance based on the number of performance validity tests failures: A cross-validation study across multiple mixed clinical samples.

Objective: This cross-sectional study examined the effect of number of Performance Validity Test (PVT) failures on neuropsychological test performance among a demographically diverse Veteran (VA) sample (n = 76) and academic medical sample (AMC; n = 128). A secondary goal was to investigate the psychometric implications of including versus excluding those with one PVT failure when cross-validating a series of embedded PVTs. Method: All patients completed the same six criterion PVTs, with the AMC sample completing three additional embedded PVTs. Neurocognitive test performance differences were examined based on number of PVT failures (0, 1, 2+) for both samples, and effect of number of criterion failures on embedded PVT performance was analyzed among the AMC sample. Results: Both groups with 0 or 1 PVT failures performed better than those with ≥2 PVT failures across most cognitive tests. There were nonsignificant differences between those with 0 or 1 PVT failures except for one test in the AMC sample. Receiver operator characteristic curve analyses found no differences in optimal cut score based on number of PVT failures when retaining/excluding one PVT failure. Conclusion: Findings support the use of ≥2 PVT failures as indicative of performance invalidity. These findings strongly support including those with one PVT failure with those with zero PVT failures in diagnostic accuracy studies, given that their inclusion reflects actual clinical practice, does not reduce sample sizes, and does not artificially deflate neurocognitive test results or inflate PVT classification accuracy statistics.

Performance validity testing via telehealth and failure rate in veterans with moderate-to-severe traumatic brain injury: A veterans affairs TBI model systems study.

BACKGROUND: The COVID-19 pandemic has led to increased utilization of teleneuropsychology (TeleNP) services. Unfortunately, investigations of performance validity tests (PVT) delivered via TeleNP are sparse. OBJECTIVE: The purpose of this study was to examine the specificity of the Reliable Digit Span (RDS) and 21-item test administered via telephone. METHOD: Participants were 51 veterans with moderate-to-severe traumatic brain injury (TBI). All participants completed the RDS and 21-item test in the context of a larger TeleNP battery. Specificity rates were examined across multiple cutoffs for both PVTs. RESULTS: Consistent with research employing traditional face-to-face neuropsychological evaluations, both PVTs maintained adequate specificity (i.e., > 90%) across previously established cutoffs. Specifically, defining performance invalidity as RDS < 7 or 21-item test forced choice total correct < 11 led to < 10%false positive classification errors. CONCLUSIONS: Findings add to the limited body of research examining and provide preliminary support for the use of the RDS and 21-item test in TeleNP via telephone. Both measures maintained adequate specificity in veterans with moderate-to-severe TBI. Future investigations including clinical or experimental "feigners" in a counter-balanced cross-over design (i.e., face-to-face vs. TeleNP) are recommended.

Validity of early-onset dementia diagnoses in VA electronic medical record administrative data.

OBJECTIVE: To determine the validity of diagnoses indicative of early-onset dementia (EOD) obtained from an algorithm using administrative data, we examined Veterans Health Administration (VHA) electronic medical records (EMRs). METHOD: A previously used method of identifying cases of dementia using administrative data was applied to a random sample of 176 cases of Post-9/11 deployed veterans under 65 years of age. Retrospective, cross-sectional examination of EMRs was conducted, using a combination of administrative data, chart abstraction, and review/consensus by board-certified neuropsychologists. RESULTS: Approximately 73% of EOD diagnoses identified using existing algorithms were identified as false positives in the overall sample. This increased to approximately 76% among those with mental health conditions and approximately 85% among those with mild traumatic brain injury (TBI; i.e. concussion). Factors related to improved diagnostic accuracy included more severe TBI, diagnosing clinician type, presence of neuroimaging data, absence of a comorbid mental health condition diagnosis, and older age at time of diagnosis. CONCLUSIONS: A previously used algorithm for detecting dementia using VHA administrative data was not supported for use in the younger adult samples and resulted in an unacceptably high number of false positives. Based on these findings, there is concern for possible misclassification in population studies using similar algorithms to identify rates of EOD among veterans. Further, we provide suggestions to develop an enhanced algorithm for more accurate dementia surveillance among younger populations.

The Word Memory Test genuine memory impairment profile discriminates genuine memory impairment from invalid performance in a mixed clinical sample with cognitive impairment.

Objective: The Word Memory Test (WMT) is a memory-based performance validity test (PVT) with adjusted interpretive criteria (Genuine Memory Impairment Profile; GMIP) proposed for those with cognitive impairment (CI). The GMIP has been criticized for poor discriminability; thus, this study sought to validate the GMIP in a mixed clinical sample. Analyses aimed to demonstrate enhanced detection of invalid neuropsychological test performance while minimizing false positives in a sample including patients with mild CI. Method: Data included 116 Veterans who completed the WMT and four criterion PVTs during clinical evaluation. This sample was 37.1% valid-CI, 33.6% valid-unimpaired, and 29.3% invalid per criterion PVTs. Group differences in WMT performance and diagnostic accuracy were assessed. Results: WMT performance significantly differed between validity groups (Wilk's Λ = .40, F[6, 109] = 27.62, p < .001, ηp2 = .60) with invalid participants scoring significantly lower across all WMT indices, with larger effect sizes for the effort subtests ( ηp2 = .44-.55) than memory subtests ( ηp2 = .16-.32). CI also had a significant effect on WMT performance (Wilk's Λ = .65, F[6, 75] = 6.66, p < .001, ηp2 = .35). Those with CI scored lower across all indices, with larger effect sizes for the memory subtests ( ηp2 = .29-.30) relative to effort subtests ( ηp2 = .18-.20). Standard WMT pass/fail criteria were sensitive (.97), but had unacceptable specificity (.66). GMIP sensitivity (.94) and specificity (.91) were robust with a DOR of 171.43. Conclusions: WMT indices were more significantly affected by performance validity than memory. However, with CI, GMIP criteria is essential to improve diagnostic accuracy and reduce false positive errors when identifying invalid performance.

Evaluating the accuracy of the Wechsler Memory Scale-Fourth Edition (WMS-IV) logical memory embedded validity index for detecting invalid test performance.

Embedded performance validity tests (PVTs) allow for continuous assessment of invalid performance throughout neuropsychological test batteries. This study evaluated the utility of the Wechsler Memory Scale-Fourth Edition (WMS-IV) Logical Memory (LM) Recognition score as an embedded PVT using the Advanced Clinical Solutions (ACS) for WAIS-IV/WMS-IV Effort System. This mixed clinical sample was comprised of 97 total participants, 71 of whom were classified as valid and 26 as invalid based on three well-validated, freestanding criterion PVTs. Overall, the LM embedded PVT demonstrated poor concordance with the criterion PVTs and unacceptable psychometric properties using ACS validity base rates (42% sensitivity/79% specificity). Moreover, 15-39% of participants obtained an invalid ACS base rate despite having a normatively-intact age-corrected LM Recognition total score. Receiving operating characteristic curve analysis revealed a Recognition total score cutoff of < 61% correct improved specificity (92%) while sensitivity remained weak (31%). Thus, results indicated the LM Recognition embedded PVT is not appropriate for use from an evidence-based perspective, and that clinicians may be faced with reconciling how a normatively intact cognitive performance on the Recognition subtest could simultaneously reflect invalid performance validity.

Restructuring Blank Spaces: The Role of Cognitive-Behavioral Interventions for Two Patients With Post-traumatic Amnesia After Severe Traumatic Brain Injury.

Differentiation of symptoms associated with post-traumatic amnesia (PTA) versus post-traumatic stress symptoms (PTSS) following trauma presents many treatment challenges among veterans and active duty service members receiving rehabilitation after traumatic brain injury (TBI). The acute phase of rehabilitation poses difficulties for amnestic individuals that may elicit classic PTA symptoms as well as premorbid PTSS, thereby activating maladaptive cognitions and an increase in agitation and arousal. Historically, explicit learning and memory strategies were considered non-efficacious with amnestic individuals until PTA resolves; therefore, rehabilitation therapies have utilized implicit learning in the initial phases of recovery. However, cognitive-behavioral therapy (CBT), which uses explicit learning and memory strategies based on cognitive, trauma, and neuropsychology lowers agitation and confusion for amnestic individuals with PTSS. In this paper, two case studies present preliminary evidence for effective implicit learning following a CBT intervention for individuals in PTA after a severe TBI receiving care. Notably, following a CBT intervention, agitation, confusion, and arousal were diminished despite having no recollection of the intervention. Thus, these cases suggest amnestic individuals in the acute recovery stage after severe TBI benefit from CBT to replace maladaptive attributions minimizing PTA and PTSS (e.g., confusion, arousal, and agitation) and improving motivation, participation, and recovery.

Cognitive impairment does not cause invalid performance: analyzing performance patterns among cognitively unimpaired, impaired, and noncredible participants across six performance validity tests.

Objective: Performance validity tests (PVTs) are essential in neuropsychological evaluations; however, it has been questioned how PVTs function in the context of cognitive impairment, and whether cognitive impairment alone is sufficient to cause PVT failure. Further, there is concern that some clinicians will disregard failed PVTs due to their perception that failures represent false-positive errors secondary to cognitive impairment. This study examined patterns associated with cognitively impaired versus noncredible performance across a battery of PVTs and neuropsychological tests. Additionally, the impact of VA service-connection and disability-seeking status on test validity was investigated. Method: A mixed-clinical sample of 103 veterans were administered six PVTs and neuropsychological tests. Performance was compared across three groups: valid-cognitively unimpaired, valid-cognitively impaired, and noncredible. Results: Significant PVT score differences and failure rates emerged across the three groups, with nonsignificant to small differences between valid-unimpaired and valid-impaired groups, and large differences between impaired and noncredible groups. In contrast, there were nonsignificant to small differences on neuropsychological tests between the valid-impaired and noncredible groups, indicating that impaired participants performed significantly better on PVTs despite comparable neurocognitive test scores. Service-connection rating itself was not associated with PVT failure, but an active disability claim to increase and/or establish service connection was associated with worse PVT performance. Conclusion: This study supports the use of multiple PVTs during evaluations of patients with varied cognitive abilities. Results indicated increased risk of PVT failure in patients who were seeking initiation/increase in service-connected payments, and shows that cognitive impairment does not cause PVT failure.

The Dot Counting Test adds up: Validation and response pattern analysis in a mixed clinical veteran sample.

OBJECTIVE: This study cross-validated the Dot Counting Test (DCT) as a performance validity test (PVT) among a mixed clinical veteran sample. Completion time and error patterns also were examined by validity group and cognitive impairment status. METHOD: This cross-sectional study included 77 veterans who completed the DCT during clinical evaluation. Seventy-four percent (N = 57) were classified as valid and 26% as noncredible (N = 20) via the Word Memory Test (WMT) and Test of Memory Malingering (TOMM). Among valid participants, 47% (N = 27) were cognitively impaired, and 53% (N = 30) were unimpaired. RESULTS: DCT performance was not significantly associated with age, education, or bilingualism. Seventy-five percent of the overall sample committed at least one error across the 12 stimulus cards; however, valid participants had a 27% higher rate of 0 errors, while noncredible participants had a 35% higher rate of ≥4 errors. Overall, noncredible individuals had significantly longer completion times, more errors, and higher E-scores. Conversely, those with cognitive impairment had longer completion times, but comparable errors to their unimpaired counterparts. Finally, DCT E-scores significantly predicted group membership with 83.1% classification accuracy and an area under the curve of .87 for identifying invalid performance. The optimal cut-score of 15 was associated with 70% sensitivity and 88% specificity. CONCLUSION: The DCT demonstrated good classification accuracy and sensitivity/specificity for identifying noncredible performance in this mixed clinical veteran sample, suggesting utility as a non-memory-based PVT with this population. Moreover, cognitive impairment significantly contributed to slower completion times, but not reduced accuracy.

Clinical utility of the Rey 15-Item Test, recognition trial, and error scores for detecting noncredible neuropsychological performance in a mixed clinical sample of veterans.

OBJECTIVE: This cross-sectional study examined the Rey 15-Item Test (RFIT), Recognition Trial, and Error Scores for identifying noncredible performance in a mixed clinical veteran sample compared to another widely used validity measure, the Test of Memory Malingering (TOMM). METHOD: Sixty-two veterans who completed the RFIT (Recall/Recognition Trials), TOMM, and Word Memory Test (WMT) during clinical evaluation were included. Using the WMT as the criterion, 71% (N = 44) were classified as valid and 29% (N = 18) as invalid. RESULTS: Among valid participants, 25% failed the RFIT Recall, whereas 78% of invalid participants passed (sensitivity: 22%; specificity: 75%; diagnostic odds ratio [DOR]: .86). The Recognition Trial increased sensitivity to 39% for identifying invalid performance, but 25% of valid participants still scored below cut-off (specificity: 75%; DOR: 1.91). RFIT Recall and Recognition Trial logistic regression and receiver operating characteristic (ROC) analyses were nonsignificant, with respective classification accuracies of 71 and 72.6% and areas under the curve (AUCs) of .52 and .55. RFIT Error Scores also failed to differentiate validity groups. In contrast, TOMM had stronger psychometric properties (sensitivity: 50%; specificity: 97.7%; DOR: 43; classification accuracy: 82.3%; AUC: .91). Moreover, RFIT Recall and Recognition failure rates were 14 and 22% greater, respectively, among those with cognitive impairment, whereas 95% of those with impairment and 100% without passed the TOMM. CONCLUSION: Despite frequent use among VA neuropsychologists, the RFIT displayed limited ability to detect noncredible performance and misclassified a large percentage of valid participants in this mixed clinical veteran sample, suggesting limited utility with this population.

Neuropsychological Evaluation in Traumatic Brain Injury.

Clinical neuropsychology is a subspecialty of professional psychology that is concerned with the scientific study and clinical application of brain-behavior relationships. Broadly defined, a neuropsychological evaluation is a flexible clinical tool that involves integration of objective, psychometric test data along with various other sources of clinical information to comprehensively elucidate the cognitive, behavioral, and emotional sequelae after traumatic brain injury (TBI). In addition to characterizing TBI sequelae, evidenced-based neuropsychological assessment can contribute to TBI patient care by aiding with prognostic assessment, measuring interval change/recovery over time (eg, resolution of posttraumatic amnesia), informing and implementing rehabilitation strategies, and evaluating the effectiveness of interventions.

Slow and Steady Does Not Always Win the Race: Investigating the Effect of Processing Speed across Five Naming Tests.

OBJECTIVE: This retrospective study investigated the effect of processing speed on confrontation naming performance via five naming tests with varying time components. METHOD: The effect of processing speed, as measured by the Wechsler Adult Intelligence Scale-Fourth Edition Processing Speed Index (PSI), and cognitive impairment were examined using Boston Naming Test, Neuropsychological Assessment Battery Naming Test, Visual Naming Test (VNT), Auditory Naming Test (ANT), and Woodcock-Johnson III Rapid Picture Naming (RPN) performance among a mixed clinical sample of 115 outpatient veterans. RESULTS: PSI scores accounted for 5%-26% of the total variance in naming test performances. Comparison of cognitively impaired versus unimpaired participants found significant differences and medium to large effect sizes (η2 = .08-.20) for all naming measures except ANT tip-of-the-tongue responses. After controlling for the effect processing speed, VNT tip-of-the-tongue responses also became non-significant, whereas significant group differences remained present for all other naming test scores, albeit with notably smaller effects sizes (η2 = .06-.10). CONCLUSIONS: Confrontation naming test performance is related to cognitive processing speed, although the magnitude of this effect varies by the demands of each naming test (i.e., largest for RPN; smallest for VNT). Thus, results argue that processing speed is important to consider for accurate clinical interpretation of naming tests, especially in the context of cognitive impairment.

The effect of perceptual reasoning abilities on confrontation naming performance: An examination of three naming tests.

INTRODUCTION: Confrontation naming tests are a common neuropsychological method of assessing language and a critical diagnostic tool in identifying certain neurodegenerative diseases; however, there is limited literature examining the visual-perceptual demands of these tasks. This study investigated the effect of perceptual reasoning abilities on three confrontation naming tests, the Boston Naming Test (BNT), Neuropsychological Assessment Battery (NAB) Naming Test, and Visual Naming Test (VNT) to elucidate the diverse cognitive functions underlying these tasks to assist with test selection procedures and increase diagnostic accuracy. METHOD: A mixed clinical sample of 121 veterans were administered the BNT, NAB, VNT, and Wechsler Adult Intelligence Scale-4th Edition (WAIS-IV) Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI) as part of a comprehensive neuropsychological evaluation. RESULTS: Multiple regression indicated that PRI accounted for 23%, 13%, and 15% of the variance in BNT, VNT, and NAB scores, respectively, but dropped out as a significant predictor once VCI was added. Follow-up bootstrap mediation analyses revealed that PRI had a significant indirect effect on naming performance after controlling education, primary language, and severity of cognitive impairment, as well as the mediating effect of general verbal abilities for the BNT (B = 0.13; 95% confidence interval, CI [.07, .20]), VNT (B = 0.01; 95% CI [.002, .03]), and NAB (B = 0.03; 95% CI [.01, .06]). CONCLUSIONS: Findings revealed a complex relationship between perceptual reasoning abilities and confrontation naming that is mediated by general verbal abilities. However, when verbal abilities were statistically controlled, perceptual reasoning abilities were found to have a significant indirect effect on performance across all three confrontation naming measures with the largest effect noted with the BNT relative to the VNT and NAB Naming Test.

Longitudinal stability of RBANS profiles in a geriatric community-dwelling sample.

This investigation is an extension of a previous study that identified four neurocognitive RBANS groups via cluster analysis in a geriatric community-dwelling sample of 699 individuals who were at least 65 years of age. Groups were examined longitudinally over a 2-year interval to establish if they exhibited marked score changes over three assessment periods. Dropout rates, onset of medical pathology, and self-reported functioning were tracked at each evaluation. Results confirmed that cluster scores were generally stable over time although the Low Immediate Memory group's Immediate Memory index score regressed upward toward the mean by the third assessment. Of interest, individuals in the Below Average group had substantial dropout between the first and third assessments. Results are interpreted through a clinical framework to explore how RBANS cluster profiles may have predictive value in general neurocognitive functioning over the observed time period and be potentially influenced by general health factors.

Quality of Life in Prodromal HD: Qualitative Analyses of Discourse from Participants and Companions.

Persons who are at risk for Huntington's Disease (HD) can be tested for the HD gene expansion before symptom onset. People with the gene expansion, but no clinical diagnosis, are in the prodromal phase of HD. This study explored quality of life (QOL) in prodromal HD. Interviews about QOL, conducted with 9 prodromal HD participants and 6 companions, were transcribed. Discourse was coded for emotional valence, content (e.g., coping, spirituality, interpersonal relationships, HD in others, and employment), and time frame (e.g., current, past, and future). Respondents were more positive than negative about the present, which was their major focus. The most common statements were about positive attitudes. Positive statements were made about spirituality, and negative statements were made about HD in other people. Relationships, employment, and coping with HD reflected both positivity and negativity. Participants and companions spoke of the future with different concerns. Applicability of findings to the clinical management of HD are discussed.

The Trail Making Test in prodromal Huntington disease: contributions of disease progression to test performance.

We examined the Trail Making Test (TMT) in a sample of 767 participants with prodromal Huntington disease (prodromal HD) and 217 healthy comparisons to determine the contributions of motor, psychiatric, and cognitive changes to TMT scores. Eight traditional and derived TMT scores were also evaluated for their ability to differentiate prodromal participants closer to estimated age of diagnosis from those farther away and prodromal individuals from healthy comparisons. Results indicate that motor signs only mildly affected Part A, and psychiatric symptoms did not affect either part. Tests of perceptual processing, visual scanning, and attention were primarily associated with Part A, and executive functioning (response inhibition, set-shifting), processing speed, and working memory were associated with Part B. Additionally, TMT scores differentiated between healthy comparisons and prodromal HD individuals as far as 9-15 years before estimated diagnosis. In participants manifesting prodromal motor signs and psychiatric symptoms, the TMT primarily measures cognition and is able to discriminate between groups based on health status and estimated time to diagnosis.

Estimating premorbid functioning in huntington's disease: the relationship between disease progression and the wide range achievement test reading subtest.

The estimation of premorbid abilities is an essential part of a neuropsychological evaluation, especially in neurodegenerative conditions. Although word pronunciation tests are one standard method for estimating the premorbid level, research suggests that these tests may not be valid in neurodegenerative diseases. Therefore, the current study sought to examine two estimates of premorbid intellect, the Wide Range Achievement Test (WRAT) Reading subtest and the Barona formula, in 93 patients with mild to moderate Huntington's disease (HD) to determine their utility and to investigate how these measures relate to signs and symptoms of disease progression. In 89% of participants, WRAT estimates were below the Barona estimates. WRAT estimates were related to worsening memory and motor functioning, whereas the Barona estimates had weaker relationships. Neither estimate was related to depression or functional capacity. Irregular word reading tests appear to decline with HD progression, whereas estimation methods based on demographic factors may be more robust but overestimate premorbid functioning.

Self-paced timing detects and tracks change in prodromal Huntington disease.

OBJECTIVE: This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington's disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC). METHOD: Participants (747 pr-HD: 188 NC) listened to tones presented at 550-ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and other demographic factors. RESULTS: Pr-HD participants showed significantly less timing precision than NC. Comparison of pr-HD and NC participants showed a significant performance difference on two task administration conditions (dominant hand: p < .0001; alternating thumbs: p < .0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t = -11.14, df = 920, p < .0001; alternating thumbs: t = -11.32, df = 918, p < .0001). Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and rate of decline increases with estimated proximity to diagnosis in both conditions (dominant hand: t = -2.85, df = 417, p = .0045; alternating thumbs: t = -3.56, df = 445, p = .0004). Effect sizes based on adjusted mean annual change ranged from -0.34 to 0.25 in the longitudinal model. CONCLUSIONS: The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically mediated improvement or maintenance of function.

Earliest functional declines in Huntington disease.

We examined the gold standard for Huntington disease (HD) functional assessment, the Unified Huntington's Disease Rating Scale (UHDRS), in a group of at-risk participants not yet diagnosed but who later phenoconverted to manifest HD. We also sought to determine which skill domains first weaken and the clinical correlates of declines. Using the UHDRS Total Functional Capacity (TFC) and Functional Assessment Scale (FAS), we examined participants from Huntington Study Group clinics who were not diagnosed at their baseline visit but were diagnosed at a later visit (N=265). Occupational decline was the most common with 65.1% (TFC) and 55.6% (FAS) reporting some loss of ability to engage in their typical work. Inability to manage finances independently (TFC 49.2%, FAS 35.1%) and drive safely (FAS 33.5%) were also found. Functional decline was significantly predicted by motor, cognitive, and depressive symptoms. The UHDRS captured early functional losses in individuals with HD prior to formal diagnosis, however, fruitful areas for expanded assessment of early functional changes are performance at work, ability to manage finances, and driving. These are also important areas for clinical monitoring and treatment planning as up to 65% experienced loss in at least one area prior to diagnosis.