Introduction to Huntington’s Disease
Huntington’s disease (HD) is a rare, genetic neurodegenerative condition featuring progressive motor, cognitive, psychiatric, and behavioral symptoms. A recent meta-analysis found incidence rates to be 0.47 per 100,000 from 1985-2022, with evidence of increased rates over the past 1-2 decades (Medina et al., 2022).
While chorea and other extrapyramidal signs are hallmarks of HD and required for diagnosis, people with HD (PwHD) experience a wide range of non-motor symptoms. These symptoms can emerge 10-15 years prior to motor symptoms and are associated with functional declines and reduced quality of life (QoL; Hamilton et al., 2003; Hendel et al., 2022; McCabe et al., 2009). The diversity of symptoms, severity, and their progressive nature require specialized care from providers knowledgeable about HD. The requirement for specialized care and the rarity of HD creates a need for multidisciplinary clinics (MDCs), as they improve follow-up rates, reduce travel burden, and improve outcomes (Ciancarelli et al., 2013; Cruickshank et al., 2015).
Due to the diverse cognitive and psychiatric symptoms, the Huntington’s Disease Society of America (HDSA) lists neuropsychology as a core multidisciplinary team member. The role of neuropsychology within MDCs requires flexibility in and integration of a variety of clinical skills (i.e., assessment, intervention, and consultation).
Neuropsychologists’ Roles within a Multidisciplinary Clinic
MDCs often benefit from neuropsychologists providing services beyond lengthy outpatient assessments, covering a wide range of services integral to comprehensive care. These roles cover care gaps common to PwHD, promote holistic conceptualization and treatment, and provide essential consultation to other team members (e.g., educating providers about accommodating cognitive dysfunction). The following will discuss 4 areas: cognitive assessment, cognitive rehabilitation (CR), brief psychological intervention, and caregiver support and psychoeducation. The importance of these roles will be highlighted, and we will reference our clinical experiences at an HDSA Center of Excellence (COE). This HDSA-COE sees patients at 4-month intervals for multidisciplinary visits. Given time constraints, neuropsychology completes serial assessments (e.g., every 18 months) that bookend regular check-ins and also offers brief CR and/or psychological intervention. These interventions do not represent full treatment but can nonetheless offer valuable skills and resources for patients and their caregivers (see Figure 1 for an example session structure).
Cognitive Assessment
PwHD tend to present early with frontal-subcortical deficits. Processing speed decline is one of the earliest features, although deficits in executive functioning, attention, learning, visuoperceptual skills, and emotion recognition are also present (Snowden, 2017). Cognitive changes have been found in up to 40-60% of individuals with premanifest-HD (Duff et al., 2010).
Cognitive assessment is particularly important for PwHD, as cognitive decline is associated with functional deficits, care need changes (e.g., placement outside the home), and disability (Ross et al., 2014). Assessment results assist with capturing current functioning, making recommendations (including treatment, such as CR), educating patients and caregivers, and tracking progression.
In the context of an MDC, cognitive assessment must be adjusted to fit time and setting limitations. Interviews and assessment batteries are targeted and shorter than outpatient evaluations. The HD-Cognitive Assessment Battery (HD-CAB) was designed as a brief (30-minute), standardized assessment for PwHD, and it yields a composite z-score sensitive to premanifest-HD and early-HD (Stout et al., 2014). More recently, the HD neuropsychology study group has provided a comprehensive hierarchical battery of tests (Considine et al., 2024), which can be applied for a flexible approach to patient needs.
Clinically, in our HDSA-COE, we conduct a clinical interview, MoCA, and neuropsychological assessment at baseline for all patients. Baseline batteries are intended to provide a comprehensive assessment across domains while respecting time limitations. Repeat visits include a cognitive check-in (e.g., repeat MoCA and discussion with patient/caregiver) with re-evaluations at 12–18 month intervals, as appropriate. Table 1 includes example batteries administered to PwHD. While there are similarities, differences in the batteries highlight how assessment can differ for various settings and purposes. For example, the HD Study group provides a range of tests to consider predominantly for outpatient contexts, whereas the time-limit of our MDC has led to choices wherein we can be comprehensive but less exhaustive (e.g., opting to use F-only phonemic fluency).
While less frequent, capacity evaluations can also be helpful, particularly when considering areas of functional independence. These often involve specific capacity questions (e.g., medical decision-making), although more extensive questions (e.g., guardianship) can also be considered and can highlight the need for proactive planning.
Cognitive Rehabilitation (CR)
PwHD are candidates for CR due to the variety of cognitive symptoms they experience. Several studies have demonstrated the benefit of CR in HD (Bartlett et al., 2020; Cruickshank et al., 2015; Moreu-Valls et al., 2025; Thompson et al., 2013; Zinzi et al., 2007), and there is growing support for CR in neurodegenerative populations (Krellman & Mercuri, 2023). However, individual treatment is best suited to early disease stages due to HD’s progressive nature. In later stages, other cognitive interventions, such as cognitive stimulation, can be considered (Saragih et al., 2022). While data is still limited for long-term effectiveness of cognitive interventions in PwHD, data from other groups, including Alzheimer’s disease (Germain et al., 2019), Parkinson’s disease (Diez-Cirarda et al., 2018), schizophrenia (Tao et al., 2015), older adults (Willis et al., 2006), and traumatic brain injury (Kennedy et al., 2022), suggest that benefits can extend at least 1-5 years after intervention.
For PwHD, CR tends to be most effective with individualized treatment planning that considers cognitive strengths and deficits, preferences, and daily life. Treatment should incorporate compensatory rehabilitation to prolong autonomy and reduce caregiver burden (Krellman & Mercuri, 2023). As the disease progresses, there should be an increased focus on environmental modifications and caregiver engagement.
CR should reference objective data from cognitive assessment paired with subjective reports from PwHD and their caregivers. Specific attention should be paid to maintaining independence, which indirectly supports psychological wellness (Krellman & Mercuri, 2023). A multidisciplinary approach is best, as research indicates improved outcomes when CR is paired with physical interventions (Maggio et al., 2024). In our clinic, cases are seen for CR on an as-needed basis. Due to the clinic model, CR sessions focus on targeted compensatory strategies that patients and caregivers can use to monitor and support abilities between visits. In cases where more extensive CR is indicated (e.g., pre-manifest or early-HD), patients may be seen on an outpatient basis.
Brief Psychological Interventions
High variability of psychiatric symptoms is present in HD, including relatively common conditions (e.g., depression), more severe presentations (e.g., psychosis), and neuropsychiatric symptoms (e.g., apathy). Psychological difficulties are overwhelmingly present, seen in up to 87% of gene expression carriers (Dale et al., 2022). Mood symptoms can appear several years before motor changes and can have a significant impact on functional capacity (Duff et al., 2007; Epping et al., 2016; Hamilton et al., 2003). Also important to PwHD is suicide risk, particularly in premanifest-HD, necessitating routine risk assessment for safety (Kachian et al., 2019).
While there is a biological basis to these changes, providers should not discount the emotional burden of the experience of HD. Patients and their families rate psychological and behavioral symptoms as primary stressors (Hamilton et al., 2003), and these symptoms significantly predict QoL and impact other symptom domains (Bilal, Harding, & Stout, 2023). Preliminary evidence points to benefits of various treatment modalities, including CBT, progressive muscle relaxation (PMR), and psychoeducation (Zarotti, Dale, Eccles, & Simpson, 2020). Data from other clinical populations which also demonstrate neuropsychiatric symptoms, such as Parkinson’s disease, have shown similar benefits from psychological interventions with benefits maintained for at least 1-6 months after treatment (Dissanayaka et al., 2017; Koychev & Okai, 2017; Moonen et al., 2021). While neuropsychologists might not provide full therapeutic services, brief psychological interventions can be valuable and are amenable to delivery within this setting. For example, anxiety could benefit from PMR, depression could be addressed via behavioral activation, and emotion dysregulation could be managed through techniques from Dialectical Behavioral Therapy. Patients and their caregivers can also be provided with resource packets, including psychoeducation and easy-to-implement activities promoting emotional wellness. For more extensive needs, neuropsychologists can utilize their connections to local therapists to facilitate appropriate referrals.
Caregiver Support and Psychoeducation
An important component of HD treatment is working with caregivers. HD caregivers experience high rates of decline in mood, personal health, and QoL, even when compared to other caregiving groups (McCabe et al., 2009), and caregiver burden also impacts patient outcomes (Torti Jr et al., 2004). Consequently, caregiver well-being should be assessed and monitored to facilitate intervention and connection to resources. For example, meeting with a neuropsychologist can serve as a prompting event to connect caregivers to case management to help navigate care needs.
Neuropsychologists also play an important role in psychoeducation, helping caregivers understand symptoms, and normalizing caregiving experiences. Neuropsychologists possess knowledge of the neurologic basis of HD symptoms as well as non-specific therapeutic and communication skills that can facilitate informative yet validating conversations. Education can increase acceptance by family members by reducing blame on the patient and reframing symptoms as a part of the disease. Also important in these conversations is planting seeds regarding future care assistance for caregivers who might not yet need or be ready to accept help. Consistent and early conversations enable caregivers to be more open to utilizing resources in the future.
Summary
HD is a neurodegenerative condition with a range of motor and non-motor symptoms. The relative rarity of HD and the need for specialized care positions MDCs as particularly beneficial. The preponderance of cognitive, behavioral, and psychiatric symptoms creates opportunities for neuropsychologists to serve in a variety of roles. Time-efficient cognitive assessments can be provided at baseline to uncover areas of concern, direct treatments and consultation, and serially track progression. If needed, capacity evaluations can be performed. However, beyond these traditional services, neuropsychologists can provide assessment-informed CR, including compensatory strategies for patients and caregivers. Further, neuropsychologists can offer brief psychological interventions for PwHD as well as assess and educate caregivers. Taking on non-traditional roles as a neuropsychologist can lead to better outcomes for patients, fulfill care needs, and bolster the utility of neuropsychology as an integral component of multidisciplinary teams.
References
Bartlett, D. M., Govus, A., Rankin, T., Lampit, A., Feindel, K., Poudel, G., … & Cruickshank, T. M. (2020). The effects of multidisciplinary rehabilitation on neuroimaging, biological, cognitive and motor outcomes in individuals with premanifest Huntington’s disease. Journal of the neurological sciences, 416, 117022.
Bilal, H., Harding, I. H., & Stout, J. C. (2024). The relationship between disease-specific psychosocial stressors and depressive symptoms in Huntington’s disease. Journal of neurology, 271(1), 289–299. https://doi.org/10.1007/s00415-023-11982-x
Ciancarelli, I., Tozzi Ciancarelli, M. G., & Carolei, A. (2013). Effectiveness of intensive neurorehabilitation in patients with Huntington’s disease. Eur J Phys Rehabil Med, 49(2), 189-95.
Considine, C. M., Rossetti, M. A., Anderson, K., Del Bene, V. A., Anderson, S. A., Celka, A. S., … & Stout, J. C. (2024). Huntington study group’s neuropsychology working group position on best practice recommendations for the clinical neuropsychological evaluation of patients with Huntington disease. The Clinical Neuropsychologist, 38(4), 984-1006.
Cruickshank, T. M., Thompson, J. A., Domínguez D, J. F., Reyes, A. P., Bynevelt, M., Georgiou‐Karistianis, N., … & Ziman, M. R. (2015). The effect of multidisciplinary rehabilitation on brain structure and cognition in Huntington’s disease: an exploratory study. Brain and behavior, 5(2), e00312.
Dale, M., Wood, A., Zarotti, N., Eccles, F., Gunn, S., Kiani, R., … & Simpson, J. (2022). Using a clinical formulation to understand psychological distress in people affected by Huntington’s disease: A descriptive, evidence-based model. Journal of Personalized Medicine, 12(8), 1222.
Díez‐Cirarda, M., Ojeda, N., Peña, J., Cabrera‐Zubizarreta, A., Lucas‐Jiménez, O., Gómez‐Esteban, J. C., … & Ibarretxe‐Bilbao, N. (2018). Long‐term effects of cognitive rehabilitation on brain, functional outcome and cognition in Parkinson’s disease. European Journal of Neurology, 25(1), 5-12.
Dissanayaka, N. N., Pye, D., Mitchell, L. K., Byrne, G. J., O’Sullivan, J. D., Marsh, R., & Pachana, N. A. (2017). Cognitive behavior therapy for anxiety in Parkinson’s disease: outcomes for patients and caregivers. Clinical Gerontologist, 40(3), 159-171.
Duff, K., Paulsen, J. S., Beglinger, L. J., Langbehn, D. R., Stout, J. C., & Predict-HD Investigators of the Huntington Study Group. (2007). Psychiatric symptoms in Huntington’s disease before diagnosis: the predict-HD study. Biological psychiatry, 62(12), 1341-1346.
Duff, K., Paulsen, J., Mills, J., Beglinger, L. J., Moser, D. J., Smith, M. M., … & Harrington, D. L. (2010). Mild cognitive impairment in prediagnosed Huntington disease. Neurology, 75(6), 500-507.
Epping, E. A., Kim, J. I., Craufurd, D., Brashers-Krug, T. M., Anderson, K. E., McCusker, E., … & PREDICT-HD Investigators and Coordinators of the Huntington Study Group. (2016). Longitudinal psychiatric symptoms in prodromal Huntington’s disease: a decade of data. American Journal of Psychiatry, 173(2), 184-192.
Germain, S., Wojtasik, V., Lekeu, F., Quittre, A., Olivier, C., Godichard, V., & Salmon, E. (2019). Efficacy of cognitive rehabilitation in Alzheimer disease: a 1-year follow-up study. Journal of Geriatric Psychiatry and Neurology, 32(1), 16-23.
Hamilton, J. M., Salmon, D. P., Corey-Bloom, J., Gamst, A., Paulsen, J. S., Jerkins, S., … & Peavy, G. (2003). Behavioural abnormalities contribute to functional decline in Huntington’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 74(1), 120-122.
Hendel, R. K., Hellem, M. N., Hjermind, L. E., Nielsen, J. E., & Vogel, A. (2022). An Exploratory Study Investigating Autonomy in Huntington’s Disease Gene Expansion Carriers. Journal of Huntington’s disease, 11(4), 373-381.
Kachian, Z. R., Cohen-Zimerman, S., Bega, D., Gordon, B., & Grafman, J. (2019). Suicidal ideation and behavior in Huntington’s disease: Systematic review and recommendations. Journal of Affective Disorders, 250, 319-329.
Kennedy, J. E., Cooper, D. B., Curtiss, G., Shelton, J. L., Bowles, A. O., Tate, D. F., … & Vanderploeg, R. D. (2022). Long-term outcomes following cognitive rehabilitation for mild traumatic brain injury: A 5-year follow-up of a cohort from the SCORE randomized clinical trial. The Journal of Head Trauma Rehabilitation, 37(6), 390-395.
Koychev, I., & Okai, D. (2017). Cognitive–behavioural therapy for non-motor symptoms of Parkinson’s disease: a clinical review. BMJ Ment Health, 20(1), 15-20.
Krellman, J. W., & Mercuri, G. (2023). Cognitive interventions for neurodegenerative disease. Current Neurology and Neuroscience Reports, 23(9), 461-468.
Maggio, M. G., Billeri, L., Cardile, D., Quartarone, A., & Calabrò, R. S. (2024). The Role of Innovation Technology in the Rehabilitation of Patients Affected by Huntington’s Disease: A Scoping Review. Biomedicines, 12(1), 39. https://doi.org/10.3390/biomedicines12010039
McCabe, M. P., Firth, L., & O’Connor, E. (2009). A comparison of mood and quality of life among people with progressive neurological illnesses and their caregivers. Journal of clinical psychology in medical settings, 16, 355-362.
Medina, A., Mahjoub, Y., Shaver, L., & Pringsheim, T. (2022). Prevalence and incidence of Huntington’s disease: an updated systematic review and meta‐analysis. Movement disorders, 37(12), 2327-2335.
Moonen, A. J., Mulders, A. E., Defebvre, L., Duits, A., Flinois, B., Köhler, S., … & Leentjens, A. F. (2021). Cognitive behavioral therapy for anxiety in Parkinsonʼs disease: a randomized controlled trial. Movement Disorders, 36(11), 2539-2548.
Moreu-Valls, A., Puig-Davi, A., Martinez-Horta, S., Kulisevsky, G., Sampedro, F., Perez-Perez, J., … & Kulisevsky, J. (2025). A randomized clinical trial to evaluate the efficacy of cognitive rehabilitation and music therapy in mild cognitive impairment in Huntington’s disease. Journal of Neurology, 272(3), 1-14.
Orth, M., & European Huntington’s Disease Network. (2011). Observing Huntington’s disease: the European Huntington’s disease network’s REGISTRY. Journal of Neurology, Neurosurgery & Psychiatry, 82(12), 1409-1412.
Ross, C. A., Aylward, E. H., Wild, E. J., Langbehn, D. R., Long, J. D., Warner, J. H., … & Tabrizi, S. J. (2014). Huntington disease: natural history, biomarkers and prospects for therapeutics. Nature Reviews Neurology, 10(4), 204-216.
Saragih, I. D., Tonapa, S. I., Saragih, I. S., & Lee, B. O. (2022). Effects of cognitive stimulation therapy for people with dementia: A systematic review and meta-analysis of randomized controlled studies. International Journal of Nursing Studies, 128, 104181.
Snowden, J. S. (2017). The neuropsychology of Huntington’s disease. Archives of Clinical Neuropsychology, 32(7), 876-887.
Stout, J. C., Queller, S., Baker, K. N., Cowlishaw, S., Sampaio, C., Fitzer‐Attas, C., … & HD‐CAB Investigators. (2014). HD‐CAB: A cognitive assessment battery for clinical trials in Huntington’s disease1, 2, 3. Movement Disorders, 29(10), 1281-1288.
Tao, J., Zeng, Q., Liang, J., Zhou, A., Yin, X., & Xu, A. (2015). Effects of cognitive rehabilitation training on schizophrenia: 2 years of follow-up. International Journal of Clinical and Experimental Medicine, 8(9), 16089.
Thompson, J. A., Cruickshank, T. M., Penailillo, L. E., Lee, J. W., Newton, R. U., Barker, R. A., & Ziman, M. R. (2013). The effects of multidisciplinary rehabilitation in patients with early‐to‐middle‐stage Huntington’s disease: a pilot study. European Journal of Neurology, 20(9), 1325-1329.
Torti Jr, F. M., Gwyther, L. P., Reed, S. D., Friedman, J. Y., & Schulman, K. A. (2004). A multinational review of recent trends and reports in dementia caregiver burden. Alzheimer Disease & Associated Disorders, 18(2), 99-109.
Willis, S. L., Tennstedt, S. L., Marsiske, M., Ball, K., Elias, J., Koepke, K. M., … & ACTIVE Study Group, F. T. (2006). Long-term effects of cognitive training on everyday functional outcomes in older adults. Jama, 296(23), 2805-2814.
Zarotti, N., Dale, M., Eccles, F., & Simpson, J. (2020). Psychological Interventions for People with Huntington’s Disease: A Call to Arms. Journal of Huntington’s disease, 9(3), 231–243. https://doi.org/10.3233/JHD-200418
Zinzi, P., Salmaso, D., De Grandis, R., Graziani, G., Maceroni, S., Bentivoglio, A., … & Jacopini, G. (2007). Effects of an intensive rehabilitation programme on patients with Huntington’s disease: a pilot study. Clinical Rehabilitation, 21(7), 603-613.
Lee Isaac, PsyD
Correspondence: lisaac@uams.edu
Chrystal Fullen, PsyD
Correspondence: cfullen@uams.edu
Hilary Clark, PhD
Correspondence: hclark@uams.edu
Jennifer Kleiner, PhD, ABPP
Board Certified in Clinical Neuropsychology
Correspondence: jskleiner@uams.edu
Table 1
This table lists example batteries administered to PwHD, including the HD-Cognitive Assessment Battery (HD-CAB), the HD study group, and those typically administered at the University of Arkansas for Medical Sciences (UAMS) HDSA-COE.
| Domain | HD-CAB | HD Study Groupa | UAMS HDSA-COEb |
|---|---|---|---|
| Screening Measures | _ | MoCA, PD-CRS | MoCA |
| Attention, Working Memory, and Processing Speed | SDMT; CANTAB One Touch Stockings | TMT-A, Digit Span, SDMT, Stroop word and color naming | TMT-A, Digit Span, RBANS: Coding or SDMT |
| Language | _ | NAB: Naming, Animal Fluency, COWAT | F-only Phonemic Fluency, Animal Fluency |
| Memory | HVLT-R | HVLT-R, BVMT-R | HVLT-R, RBANS: Figure Recall |
| Visuospatial | _ | RCFT-Copy, RBANS-LO | RBANS: Figure Copy |
| Socio-Emotional | Emotion Recognition | ACS-Affect Recognition | _ |
| Executive Functioning | TMT-B | TMT-B, Stroop color/word, DKEFS: Tower, WCST | TMT-B, DKEFS: Color Word Interference |
| Motor and Sensory | Paced Tapping | Grooved Pegboard, BSIT | _ |
| Premorbid Functioning | _ | ToPF | _ |
| Patient-Report Measures | _ | PHQ-9, GAD-7, FrSBE, PBA-s, HD-CRFS, ESS, PSQI, Anosognosia Scale | GDS-SF/GAI, OR PHQ-9/GAD-7, OR BAI/BDI-2 |
| Collateral-Report Measures | _ | NPI-Q, FrSBE | ZBI-22 |
a The HD study group provides a range of exemplar and alternative tests that can be considered. The included tests represent only exemplars in the stated domains. Please reference the original work by Considine et al. (2024) for the full list of measures.
b Decisional points of the UAMS battery are based on clinician discretion considering patient factors, such as age and degree of cognitive and motor dysfunction.
Test acronyms in order of appearances: SDMT: Symbol Digit Modality Test; CANTAB: Cambridge Neuropsychological Test Automated Battery; HVLT-R: Hopkins Verbal Learning Test – Revised; TMT: Trail-Making Test; MoCA: Montreal Cognitive Assessment; PD-CRS: Parkinson’s Disease – Cognitive Rating Scale; NAB: Neuropsychological Assessment Battery; COWAT: Controlled Oral Word Association Test; BVMT-R: Brief Visual Memory Test-Revised; RCFT: Rey-Osterrieth Complex Figure Test; RBANS: Repeatable Battery for the Assessment of Neuropsychological Status; LO: Judgment of Line Orientation Test; D-KEFS: Delis-Kaplan Executive Function System; WCST: Wisconsin Card Sorting Test; B-SIT: Brief Smell Identification Test; ToPF: Test of Premorbid Functioning; PHQ-9: Patient Health Questionnaire; GAD-7: Generalized Anxiety Disorder Scale; FrSBe: Frontal Systems Behavior Scale; PBA-s: Short Problems Behavior Assessment for Huntington Disease; HD-CFRS: Huntington’s Disease-Cognitive Functional Rating Scale; ESS: Epworth Sleepiness Scale; PSQI: Pittsburgh Sleep Quality Index; NPI-Q: Neuropsychiatric Inventory Questionnaire; GDS-SF: Geriatric Depression Scale – Short Form; GAI: Geriatric Anxiety Inventory; BAI: Beck Anxiety Inventory; BDI-II: Beck Depression Inventory-Second Edition; and ZBI: Zarit Burden Interview.
Figure 1
This figure demonstrates example sessions that would be conducted in a multidisciplinary clinic for Huntington’s Disease. It illustrates the role flexibility and shift in services provided across the HD spectrum, albeit on a shortened timescale.
