Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

Cognitive Dysfunction in Non-CNS Metastatic Cancer: Comparing Brain Metastasis, Non-CNS Metastasis, and Healthy Controls.

Limited research has compared cognition of people with non-central nervous system metastatic cancer (NCM) vs. metastatic brain cancer (BM). This prospective cross-sectional study was comprised 37 healthy controls (HC), 40 NCM, and 61 BM completing 10 neuropsychological tests. The NCM performed below HCs on processing speed and executive functioning tasks, while the BM group demonstrated lower performance across tests. Tasks of processing speed, verbal fluency, and verbal memory differentiated the clinical groups (BM < NCM). Nearly 20% of the NCM group was impaired on at least three neuropsychological tests whereas approximately 40% of the BM group demonstrated the same level of impairment.

Neurocognitive and psychiatric outcomes associated with postacute COVID-19 infection without severe medical complication: a meta-analysis.

BACKGROUND: Cognitive symptoms are often reported by those with a history of COVID-19 infection. No comprehensive meta-analysis of neurocognitive outcomes related to COVID-19 exists despite the influx of studies after the COVID-19 pandemic. This study meta-analysed observational research comparing cross-sectional neurocognitive outcomes in adults with COVID-19 (without severe medical/psychiatric comorbidity) to healthy controls (HCs) or norm-referenced data. METHODS: Data were extracted from 54 studies published between January 2020 and June 2023. Hedges' g was used to index effect sizes, which were pooled using random-effects modelling. Moderating variables were investigated using meta-regression and subgroup analyses. RESULTS: Omnibus meta-analysis of 696 effect sizes extracted across 54 studies (COVID-19 n=6676, HC/norm-reference n=12 986; average time since infection=~6 months) yielded a small but significant effect indicating patients with COVID-19 performed slightly worse than HCs on cognitive measures (g=-0.36; 95% CI=-0.45 to -0.28), with high heterogeneity (Q=242.30, p<0.001, τ=0.26). Significant within-domain effects was yielded by cognitive screener (g=-0.55; 95% CI=-0.75 to -0.36), processing speed (g=-0.44; 95% CI=-0.57 to -0.32), global cognition (g=-0.40; 95% CI=-0.71 to -0.09), simple/complex attention (g=-0.38; 95% CI=-0.46 to -0.29), learning/memory (g=-0.34; 95% CI=-0.46 to -0.22), language (g=-0.34; 95% CI=-0.45 to -0.24) and executive function (g=-0.32; 95% CI=-0.43 to -0.21); but not motor (g=-0.40; 95% CI=-0.89 to 0.10), visuospatial/construction (g=-0.09; 95% CI=-0.23 to 0.05) and orientation (g=-0.02; 95% CI=-0.17 to 0.14). COVID-19 samples with elevated depression, anxiety, fatigue and disease severity yielded larger effects. CONCLUSION: Mild cognitive deficits are associated with COVID-19 infection, especially as detected by cognitive screeners and processing speed tasks. We failed to observe clinically meaningful cognitive impairments (as measured by standard neuropsychological instruments) in people with COVID-19 without severe medical or psychiatric comorbidities.

Microstructural white matter abnormalities in Lesch-Nyhan disease.

Lesch-Nyhan disease is a rare, sex-linked, genetic neurodevelopmental disorder that is characterized by hyperuricemia, dystonia, cognitive impairment and recurrent self-injury. We previously found reduced brain white matter volume in patients with Lesch-Nyhan disease compared with healthy adults using voxel-based morphometry. Here, we address the structural integrity of white matter via diffusion tensor imaging. We hypothesized that white matter integrity would be decreased in men with Lesch-Nyhan disease and to a lesser extent in men with a milder variant of the disease (Lesch-Nyhan variant) relative to healthy men. After acquiring diffusion-weighted brain images from Lesch-Nyhan disease (n = 5), Lesch-Nyhan variant (n = 6) and healthy participants (n = 10), we used both tract-based spatial statistics and a regions of interest approach to analyse between-group fractional anisotropy differences. We first replicated earlier findings of reduced intracranial, grey matter and white matter volumes in patients. We then discovered marked reductions of fractional anisotropy relative to the healthy control group. The Lesch-Nyhan disease group showed more pronounced reductions in white matter integrity than the Lesch-Nyhan variant group. In addition to whole brain fractional anisotropy group differences, reductions in white matter integrity were observed in the corpus callosum, corona radiata, cingulum, internal capsule and superior longitudinal fasciculus. Moreover, the variant group had attenuated dystonia severity symptoms and cognitive deficits. These findings highlight the need to better understand the role of white matter in Lesch-Nyhan disease.

Cognitive Intra-individual Variability in HIV: an Integrative Review.

Nearly 30-50% of people living with HIV experience HIV-Associated Neurocognitive Disorder (HAND). HAND indicates performance at least one standard deviation below the normative mean on any two cognitive domains. This method for diagnosing or classifying cognitive impairment has utility, however, cognitive intraindividual variability provides a different way to understand cognitive impairment. Cognitive intraindividual variability refers to the scatter in cognitive performance within repeated measures of the same cognitive test (i.e., inconsistency) or across different cognitive tests (i.e., dispersion). Cognitive intraindividual variability is associated with cognitive impairment and cognitive decline in various clinical populations. This integrative review of 13 articles examined two types of cognitive intraindividual variability in people living with HIV, inconsistency and dispersion. Cognitive intraindividual variability appears to be a promising approach to detect subtle cognitive impairments that are not captured by traditional mean-based neuropsychological testing. Greater intraindividual variability in people living with HIV has been associated with: 1) poorer cognitive performance and cognitive decline, 2) cortical atrophy, both gray and white matter volume, 3) poorer everyday functioning (i.e., driving simulation performance), specifically medication adherence, and 4) even mortality. This inspires future directions for research. First, greater cognitive intraindividual variability may reflect a greater task demand on executive control to harness and regulate cognitive control over time. By improving executive functioning through cognitive training, it may reduce cognitive intraindividual variability which could slow down cognitive decline. Second, cognitive intraindividual variability may be reconsidered in prior cognitive intervention studies in which only mean-based cognitive outcomes were used. It is possible that such cognitive interventions may actually improve cognitive intraindividual variability, which could have clinical relevance.

Neuropsychological Functioning in Primary Dystonia: Updated and Expanded Multidomain Meta-Analysis.

BACKGROUND: Primary dystonia is conventionally considered as a motor disorder, though an emerging literature reports associated cognitive dysfunction. OBJECTIVES: Here, we conducted meta-analyses on studies comparing clinical measures of cognition in persons with primary dystonia and healthy controls (HCs). METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and PsycINFO (January 2000-October 2020). Analyses were modeled under random effects. We used Hedge's g as a bias-corrected estimate of effect size, where negative values indicate lower performance in dystonia versus controls. Between-study heterogeneity and bias were primarily assessed with Cochran's Q, I2 , and Egger's regression. RESULTS: From 866 initial results, 20 studies met criteria for analysis (dystonia n = 739, controls n = 643; 254 effect sizes extracted). Meta-analysis showed a significant combined effect size of primary dystonia across all studies (g = -0.56, P < 0.001), with low heterogeneity (Q = 25.26, P = 0.15, I2  = 24.78). Within-domain effects of primary dystonia were motor speed = -0.84, nonmotor speed = -0.83, global cognition = -0.65, language = -0.54, executive functioning = -0.53, learning/memory = -0.46, visuospatial/construction = -0.44, and simple/complex attention = -0.37 (P-values <0.01). High heterogeneity was observed in the motor/nonmotor speed and learning/memory domains. There was no evidence of publication bias. Moderator analyses were mostly negative but possibly underpowered. Blepharospasm samples showed worse performance than other focal/cervical dystonias. Those with inherited (ie, genetic) disease etiology demonstrated worse performance than acquired. CONCLUSIONS: Dystonia patients consistently demonstrated lower performances on neuropsychological tests versus HCs. Effect sizes were generally moderate in strength, clustering around -0.50 SD units. Within the speed domain, results suggested cognitive slowing beyond effects from motor symptoms. Overall, findings indicate dystonia patients experience multidomain cognitive difficulties, as detected by neuropsychological tests. © 2022 International Parkinson and Movement Disorder Society.

Neuropsychological Assessment of the Aging Physician: A Review & Commentary.

Late-career physicians (LCPs) are at risk for cognitive changes that may affect their ability to practice medicine. This review aggregates and discusses research that has examined cognitive functioning among physicians, typically when clinically referred for various medical and psychological reasons that may interfere with their ability to practice medicine. Special consideration is devoted to the role of approaches for examining cognitive functioning (e.g., cognitive screening, cognitive testing, & neuropsychological assessment), normative challenges, and cultural factors that should be considered when evaluating a physician. Based on published studies, there is evidence supportive of the use of cognitive testing and neuropsychological assessment among physicians in a fitness for duty setting. However, prospective studies designed to identify physicians at-risk (i.e., to prevent medical error) are lacking. Additional research is warranted to establish physician-based normative reference groups and aid in test interpretation and prognostication. Moreover, given limitations associated with cognitive testing in isolation, there is a potential role for comprehensive neuropsychological assessment to identify cognitive changes in physicians and provide a supportive pathway to preserve physicians' ability to practice medicine.

Increased odds and predictive rates of MMPI-2-RF scale elevations in patients with psychogenic non-epileptic seizures and observed sex differences.

OBJECTIVE: The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a self-report instrument, previously shown to differentiate patients with epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). At present, the odds of MMPI-2-RF scale elevations in PNES patients, as well as the diagnostic predictive value of such scale elevations, remain largely unexplored. This can be of clinical utility, particularly when a diagnosis is uncertain. METHOD: After looking at mean group differences, we applied contingency table derived odds ratios to a sample of ES (n=92) and PNES (n=77) patients from a video EEG (vEEG) monitoring unit. We also looked at the positive and negative predictive values (PPV, NPV), as well as the false discovery rate (FDR) and false omission rate (FOR) for scales found to have increased odds of elevation in PNES patients. This was completed for the overall sample, as well as the sample stratified by sex. RESULTS: The odds of elevations related to somatic concerns, negative mood, and suicidal ideation in the PNES sample ranged from 2 to 5 times more likely. Female PNES patients had 3-6 times greater odds of such scale elevations, while male PNES patients had odds of 5-15 times more likely. PPV rates ranged from 53.66% to 84.62%, while NPV rates ranged from 47.52% to 90.91%. FDR across scales ranged from 15.38% to 50%, while the FOR ranged from 9.09% to 52.47%. CONCLUSIONS: Consistent with prior research, PNES patients have greater odds of MMPI-2-RF scale elevations, particularly related to somatic concerns and mood disturbance. Female PNES patients endorsed greater emotional distress, including endorsement of suicide related items. Elevations of these scales could aid in differentiating PNES from ES patients, although caution is warranted due to the possibility of both false positives and the incorrect omissions of PNES cases.

Severe multisensory speech integration deficits in high-functioning school-aged children with Autism Spectrum Disorder (ASD) and their resolution during early adolescence.

Under noisy listening conditions, visualizing a speaker's articulations substantially improves speech intelligibility. This multisensory speech integration ability is crucial to effective communication, and the appropriate development of this capacity greatly impacts a child's ability to successfully navigate educational and social settings. Research shows that multisensory integration abilities continue developing late into childhood. The primary aim here was to track the development of these abilities in children with autism, since multisensory deficits are increasingly recognized as a component of the autism spectrum disorder (ASD) phenotype. The abilities of high-functioning ASD children (n = 84) to integrate seen and heard speech were assessed cross-sectionally, while environmental noise levels were systematically manipulated, comparing them with age-matched neurotypical children (n = 142). Severe integration deficits were uncovered in ASD, which were increasingly pronounced as background noise increased. These deficits were evident in school-aged ASD children (5-12 year olds), but were fully ameliorated in ASD children entering adolescence (13-15 year olds). The severity of multisensory deficits uncovered has important implications for educators and clinicians working in ASD. We consider the observation that the multisensory speech system recovers substantially in adolescence as an indication that it is likely amenable to intervention during earlier childhood, with potentially profound implications for the development of social communication abilities in ASD children.

From Practice to Public Health: Broadening Neuropsychology's Reach & Value-An Introduction to the National Academy of Neuropsychology's 2022 Annual Conference Special Issue.

This special issue is centered around presentations from the National Academy of Neuropsychology 2022 Annual Conference. The theme of the conference, "From Practice to Public Health: Broadening Neuropsychology's Reach & Value" is pivotal for the field's future. With an ever-shifting technological landscape and recent changes in clinical practice post-COVID, we are left wondering how neuropsychology will develop. How will we use biomedical and technological advances, such as blood-based Alzheimer's disease biomarkers or passive digital recordings, to improve clinical care and further expand our understanding of disease mechanisms? As neuropsychologists, how can we use our expertise to empirically inform public health policy? The diagnosis and treatment of post-acute sequelae of COVID-19, the identification and characterization of post-pandemic educational setbacks, and the adaptation of new technological and diagnostic advances into clinical practice workflows represent a vital set of new challenges and opportunities poised to disrupt traditional modes of practice. The articles in this special issue convey the role of neuropsychology in addressing these emerging issues and illustrate how and why neuropsychology is well positioned to be at the forefront of clinical practice and scientific advancements.

Neural correlates of audiovisual narrative speech perception in children and adults on the autism spectrum: A functional magnetic resonance imaging study.

Autistic individuals show substantially reduced benefit from observing visual articulations during audiovisual speech perception, a multisensory integration deficit that is particularly relevant to social communication. This has mostly been studied using simple syllabic or word-level stimuli and it remains unclear how altered lower-level multisensory integration translates to the processing of more complex natural multisensory stimulus environments in autism. Here, functional neuroimaging was used to examine neural correlates of audiovisual gain (AV-gain) in 41 autistic individuals to those of 41 age-matched non-autistic controls when presented with a complex audiovisual narrative. Participants were presented with continuous narration of a story in auditory-alone, visual-alone, and both synchronous and asynchronous audiovisual speech conditions. We hypothesized that previously identified differences in audiovisual speech processing in autism would be characterized by activation differences in brain regions well known to be associated with audiovisual enhancement in neurotypicals. However, our results did not provide evidence for altered processing of auditory alone, visual alone, audiovisual conditions or AV- gain in regions associated with the respective task when comparing activation patterns between groups. Instead, we found that autistic individuals responded with higher activations in mostly frontal regions where the activation to the experimental conditions was below baseline (de-activations) in the control group. These frontal effects were observed in both unisensory and audiovisual conditions, suggesting that these altered activations were not specific to multisensory processing but reflective of more general mechanisms such as an altered disengagement of Default Mode Network processes during the observation of the language stimulus across conditions.

An Exploratory Pilot Study of Neuropsychological Performance in Two Huntington Disease Centers of Excellence Clinics.

OBJECTIVES: To describe the characteristics of patients receiving a clinical referral for neuropsychological evaluation in two Huntington's Disease Society of America Centers of Excellence (HDSA COE). In this exploratory pilot study, we used an empirically supported clinical neuropsychological battery to assess differences in cognitive performance between premanifest and manifest HD patient groups (compared with each other and normative expectations). METHOD: Clinical data from 76 adult genetically confirmed patients referred for neuropsychological evaluations was retrospectively collected from two HDSA COEs. ANOVA and Chi-square tests were used to compare variables between pre-manifest (n = 14) and manifest (n = 62) groups for demographic, cognitive, neuropsychiatric, and disease severity variables. RESULTS: Our clinics serviced a disproportionate number of motor manifest patients. Six measures were excluded from analyses due to infrequent administration. The full WAIS-IV Digit Span was disproportionately administered to the manifest group. The premanifest group showed stronger cognitive performance with effect sizes in the large range on subtests of the WAIS-IV Digit Span, HVLT-R, SDMT, and verbal fluency. CONCLUSIONS: This is the first study to assess an empirically supported neuropsychological research battery in a clinical setting with a relatively large sample size given the rarity of HD. The battery adequately captured areas of impairment across the disease spectrum. Application of the current battery with larger premanifest samples is warranted.

Formal Neuropsychological Testing: Test Batteries, Interpretation, and Added Value in Practice.

Neuropsychologists evaluate patients for cognitive decline and dementia, using validated psychometric tests, along with behavioral observation, record review, clinical interview, and information about psychological functioning, to evaluate brain-behavior relationships and aid in differential diagnosis and treatment planning. Also considered are premorbid functioning, education, sex, socioeconomic status, primary language, culture, and race-related health disparities when selecting tests, interpreting performance, and providing a diagnostic impression. Neuropsychologists provide diagnostic clarity, explain symptoms and likely disease course to patients and family members, and assist the family with future planning, behavioral management strategies, and ways to mitigate caregiver burden.

Longitudinal associations of anticholinergic medications on cognition and possible mitigating role of physical activity.

BACKGROUND: Many older adults take at least one prescription medication with anticholinergic (ACH) activity, which can impact the central nervous system and can lead to cognitive decline and impairment especially in an aging population susceptible to cognitive changes. We examined this relationship between ACH burden and cognitive function in middle-aged and older adults. We further determined if increased activity levels mitigated the relationships between ACH burden and cognition. METHODS: Data from The Reasons for Geographic and Racial Differences in Stroke project were used. We included 20,575 adults aged ≥45 years with longitudinal cognitive testing. The anticholinergic cognitive burden (ACB) scale was used to assess for ACH use and overall burden. Cognitive data included an overall composite score, a memory, and verbal fluency composites. Mixed effects models were conducted to determine if cognitive function worsened over time for participants with higher ACB (>3) scores. The full model adjusted for age, sex, race, education, diabetes, hypertension, cardiovascular disease, congestive heart failure, and dyslipidemia, self-reported physical activity (PA) and depressive symptoms. RESULTS: A significant relationship between ACH burden and composite cognitive scores was found (p = <0.001), with those with higher ACB showing more rapid cognitive decline over time. There was an effect of age for participants with higher ACB (>3) scores and ACB as a continuous variable. Baseline PA level was associated with less cognitive decline over time and this effect was greater in older cohorts. CONCLUSIONS: We observed an effect of ACHs on cognition in adults ≥45 years old that worsened with age. ACH users showed more cognitive effects, whereas PA emerged as a possible mitigating factor.

Alternative patterns of deep brain stimulation in neurologic and neuropsychiatric disorders.

Deep brain stimulation (DBS) is a widely used clinical therapy that modulates neuronal firing in subcortical structures, eliciting downstream network effects. Its effectiveness is determined by electrode geometry and location as well as adjustable stimulation parameters including pulse width, interstimulus interval, frequency, and amplitude. These parameters are often determined empirically during clinical or intraoperative programming and can be altered to an almost unlimited number of combinations. Conventional high-frequency stimulation uses a continuous high-frequency square-wave pulse (typically 130-160 Hz), but other stimulation patterns may prove efficacious, such as continuous or bursting theta-frequencies, variable frequencies, and coordinated reset stimulation. Here we summarize the current landscape and potential clinical applications for novel stimulation patterns.

Predictors of an Active Lifestyle in Middle-Aged and Older Adults with HIV in the United States Deep South.

Background and Purpose: An active lifestyle is important for health maintenance and disease prevention. This study was to examine what factors predict an active lifestyle in HIV+ and HIV- adults from the United States Deep South. Methods: The sample included 279 participants (174 HIV+ and 105 HIV-) who completed a comprehensive assessment. An active lifestyle composite was created using variables of employment status, level of social support, level of physical activity, and diet. Correlations and regression analyses were conducted between the active lifestyle composite and possible predictors for all (HIV+ and HIV-), HIV+, and HIV- participants, respectively. Results: Lower levels of depression, higher socioeconomic status (SES), and younger age were significant predictors of a more active lifestyle for the full sample, HIV+, and HIV- participants, respectively. Conclusion: SES and depression represent important factors influencing engagement in an active lifestyle in PLWH. Such factors should be considered when developing and implementing lifestyle interventions.

Within-Person Test Score Distributions: How Typical Is "Normal"?

We evaluated within-person variability across a cognitive test battery by analyzing the shape of the distribution of each individual's scores within a battery of tests. We hypothesized that most healthy adults would produce test scores that are normally distributed around their own personal battery-wide, within-person (wp) mean. Using cross-sectional data from 327 neurologically healthy adults, we computed each person's mean, standard deviation, skew, and kurtosis for 30 neuropsychological measures. Raw scores were converted to T-scores using three degrees of calibration: (a) none, (b) age, and (c) age, sex, race, education, and estimated premorbid IQ. Regardless of calibration, no participant showed abnormal within-person skew (wpskew) and only 10 (3.1%) to 16 (4.9%) showed wpkurtosis greater than 2. If replicated in other samples and measures, these findings could illuminate how healthy individuals are endowed with different cognitive abilities and provide the foundation for a new method of inference in clinical neuropsychology.

A rationale and framework for addressing physician cognitive impairment.

Medical error is costly, in terms of the health and wellbeing of the patient, their family, and the financial burden placed on the medical system. Reducing medical error is paramount to minimizing harm and improving outcomes. One potential source of medical error is physician cognitive impairment. Determining how to effectively assess and mange physician cognitive impairment is an important, albeit difficult problem to address. There have been calls and attempts to implement age-based cognitive screening, but this approach is not optimal. Instead, we propose that neuropsychological assessment is the gold standard for fitness-for-duty evaluations and that there is a need for the development of physician-based, normative data to improve these evaluations. Here, we outline the framework of our research protocol in a large, academic medical center, in partnership with hospital leadership and legal counsel, which can be modeled by other medical centers. With high rates of physician burnout and an aging physician population, the United States is facing a looming public health crisis that requires proactive management.

Huntington Study Group's Neuropsychology Working Group: Implementing Non-Motor Diagnostic Criteria.

Background: The clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD-consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non-motor diagnostic criteria for HD. Objectives: To provide (1) a recommended clinical approach toward non-motor diagnostic criteria in persons with HD and facilitation of accurate diagnosis; (2) recommended practices for medical treatment providers to screen and longitudinally monitor non-motor signs of HD. Methods: The Huntington Study Group re-established the Neuropsychology Working Group, then recruited a multi-disciplinary group of neuropsychologists, neurologists, and psychiatrists to conduct an unstructured literature review and discuss expert opinions on practice, to facilitate an informal consensus opinion to accomplish the objectives. Results: The opinion and an example protocol for medical treatment providers to screen, monitor, and triage non-motor signs and symptoms of Huntington's disease is provided. Conclusions: Clinical diagnosis of non-motor HD is empirically justified and clinically important. Screening and triage by non-neuropsychologist clinicians can aid in detecting and monitoring non-motor Huntington's disease manifestation. The Neuropsychology Working Group consensus advances good clinical practice, clinical research, and quality of life. A companion position paper presenting the details of our consensus opinion regarding evidence-based guidelines for neuropsychological practice is forthcoming.