Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-26T07:38:54.508Z Has data issue: false hasContentIssue false
  • English
  • Français

Apathy predicts rate of cognitive decline over 24 months in premanifest Huntington's disease

Published online by Cambridge University Press:  17 February 2020

S. C. Andrews ,
D. R. Langbehn ,
D. Craufurd ,
A. Durr ,
B. R. Leavitt ,
R. A. Roos ,
S. J. Tabrizi ,
J. C. Stout Open the ORCID record for J. C. Stout [Opens in a new window]  and
the TRACK-HD Investigators
S. C. Andrews
Affiliation:
School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia Neuroscience Research Australia, Sydney, NSW, Australia School of Psychology, University of New South Wales, Sydney, NSW, Australia
D. R. Langbehn
Affiliation:
Department of Psychiatry, University of Iowa, Iowa City, USA
D. Craufurd
Affiliation:
Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
A. Durr
Affiliation:
Sorbonne Université, Institut du Cerveau et de la Moelle épinière (ICM), University Hospital Pitié-Salpêtrière, AP-HP, Inserm U 1127, CNRS UMR 7225, Paris, France
B. R. Leavitt
Affiliation:
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada
R. A. Roos
Affiliation:
Department Neurology LUMC, Universiteit Leiden, Leiden, The Netherlands
S. J. Tabrizi
Affiliation:
Department of Neurodegenerative Diseases, University College London, Queen Square Institute of Neurology, and National Hospital for Neurology and Neurosurgery, London, UK
J. C. Stout*
Affiliation:
School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia
*
Author for correspondence: J. C. Stout, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design.

Methods

A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months.

Results

In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline.

Conclusions

Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline.

Keywords

ApathycognitiondepressionHuntington's disease
Type
Original Articles
Information
Psychological Medicine , Volume 51 , Issue 8 , June 2021 , pp. 1338 - 1344
Check for updates
Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

TRACK-HD Investigators:

Canada – A Coleman, R Dar Santos, J Decolongon, A Sturrock (University of British Columbia, Vancouver).

France – E Bardinet, C Jauff ret, D Justo, S Lehericy, C Marelli, K Nigaud, R Valabrègue (APHP, Hôpital Salpêtriere, Paris).

Germany – N Bechtel, R Reilmann (University of Münster, Münster); A Hoff man, P Kraus (University of Bochum, Bochum); B Landwehrmeyer (University of Ulm)

Netherlands – SJA van den Bogaard, E M Dumas, J van der Grond, EP t'Hart, C Jurgens, M-N Witjes-Ane (Leiden University Medical Centre, Leiden).

UK – N Arran, J Callaghan (St Mary's Hospital, Manchester); C Frost, R Jones (London School of Hygiene and Tropical Medicine, London); N Fox, N Hobbs, N Lahiri, R Ordidge, G Owen, T Pepple, J Read, M Say, R Scahill, E Wild (University College London, London); S Keenan (Imperial College London, London); D M Cash (IXICO, London); S Hicks, C Kennard (Oxford)

USA – E Axelson, H Johnson, D Langbehn, C Wang (University of Iowa, Iowa City, IA); S Lee, W Monaco, H Rosas (Massachusetts General Hospital, Harvard, MA); C Campbell, S Queller, K Whitlock (Indiana University, IN).

Australia – C Campbell, M Campbell, E Frajman, C Milchman, A O'Regan (Monash University, Victoria).

References

Andrews, S. C., Craufurd, D., Durr, A., Leavitt, B. R., Roos, R. A., Tabrizi, S. J., … The Track HD Investigators (2018). Executive impairment is associated with unawareness of neuropsychiatric symptoms in premanifest and early Huntington's disease. Neuropsychology, 32(8), 958–965.CrossRefGoogle ScholarPubMed
Baake, V., Coppen, E. M., van Duijn, E., Dumas, E. M., van den Bogaard, S. J. A., Scahill, R. I., & Track HD Investigators (2018). Apathy and atrophy of subcortical brain structures in Huntington's disease: A two-year follow-up study. NeuroImage: Clinical, 19, 66–70.CrossRefGoogle ScholarPubMed
Baudic, S., Maison, P., Dolbeau, G., Boissé, M.-F., Bartolomeo, P., Dalla Barba, G., & Bachoud-Lévi, A.-C. (2006). Cognitive impairment related to apathy in early Huntington's disease. Dementia and Geriatric Cognitive Disorders, 21(5–6), 316–321.10.1159/000091523CrossRefGoogle ScholarPubMed
Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for the beck depression inventory-II. San Antonio, TX: Psychological Corporation.Google Scholar
Callaghan, J., Stopford, C., Arran, N., Boisse, M. F., Coleman, A., Santos, R. D., & Craufurd, D. (2015). Reliability and factor structure of the short problem behaviors assessment for Huntington's disease (PBA-s) in the TRACK-HD and REGISTRY studies. Journal of Neuropsychiatry and Clinical Neurosciences, 27(1), 59–64.10.1176/appi.neuropsych.13070169CrossRefGoogle ScholarPubMed
Carpenter, C., & Kenward, M. (2013). Multiple imputation and its application. New York: Wiley.10.1002/9781119942283CrossRefGoogle Scholar
Delmaire, C., Dumas, E. M., Sharman, M. A., van den Bogaard, S. J. A., Valabregue, R., Jauffret, C., & Lehéricy, S. (2013). The structural correlates of functional deficits in early Huntington's disease. Human Brain Mapping, 34(9), 2141–2153.CrossRefGoogle ScholarPubMed
Dorsey, E. R., Beck, C. A., Darwin, K., Nichols, P., Brocht, A. F. D., Biglan, K. M., & Shoulson, I. (2013). Natural history of Huntington disease. JAMA neurology, 70(12), 1520–1530.Google ScholarPubMed
Duff, K., Paulsen, J. S., Beglinger, L. J., Langbehn, D. R., Wang, C., Stout, J. C., & Predict HD Investigators of the HSG (2010). “Frontal” behaviors before the diagnosis of Huntington's disease and their relationship to markers of disease progression: Evidence of early lack of awareness. The Journal of Neuropsychiatry and Clinical Neurosciences, 22(2), 196–207.CrossRefGoogle Scholar
Dujardin, K., Sockeel, P., Delliaux, M., Destee, A., & Defebvre, L. (2009). Apathy may herald cognitive decline and dementia in Parkinson's disease. Movement Disorders, 24(16), 2391–2397.CrossRefGoogle ScholarPubMed
Garcia-Ramos, R., Villanueva, C., del Val, J., & Matias-Guiu, J. (2010). Apathy in Parkinson's disease. Neurologia (Barcelona, Spain), 25(1), 40–50.Google ScholarPubMed
Hart, E. P., Dumas, E. M., Schoonderbeek, A., Wolthuis, S. C., van Zwet, E. W., & Roos, R. A. (2014). Motor dysfunction influence on executive functioning in manifest and premanifest Huntington's disease. Movement Disorders, 29(3), 320–326.CrossRefGoogle ScholarPubMed
Hedner, M., Larsson, M., Arnold, N., Zucco, G. M., & Hummel, T. (2010). Cognitive factors in odor detection, odor discrimination, and odor identification tasks. Journal of Clinical and Experimental Neuropsychology, 32(10), 1062–1067.CrossRefGoogle ScholarPubMed
Huntington Study Group (1996). Unified Huntington's disease rating scale: Reliability and consistency. Movement Disorders, 11, 136–142.CrossRefGoogle Scholar
Knight, M. J., & Baune, B. T. (2018). Cognitive dysfunction in major depressive disorder. Current Opinion in Psychiatry, 31(1), 26–31.CrossRefGoogle ScholarPubMed
Larsson, M., Finkel, D., & Pedersen, N. L. (2000). Odor identification: Influences of age, gender, cognition, and personality. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 55(5), 304–310.CrossRefGoogle Scholar
Levy, R., & Dubois, B. (2006). Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cerebral Cortex, 16(7), 916–928.CrossRefGoogle ScholarPubMed
Martinez-Horta, S., Perez-Perez, J., Sampedro, F., Pagonabarraga, J., Horta-Barba, A., Carceller-Sindreu, M., & Kulisevsky, J. (2018). Structural and metabolic brain correlates of apathy in Huntington's disease. Movement Disorders, 33(7), 1151–1159.CrossRefGoogle ScholarPubMed
Martinez-Horta, S., Perez-Perez, J., van Duijn, E., Fernandez-Bobadilla, R., Carceller, M., Pagonabarraga, J., & Kulisevsky, J. (2016). Neuropsychiatric symptoms are very common in premanifest and early stage HD. Parkinsonism & Related Disorders, 25, 58–64.CrossRefGoogle Scholar
McNally, G., Rickards, H., Horton, M., & Craufurd, D. (2015). Exploring the validity of the short version of the problem behaviours assessment (PBA-s) for Huntington's disease: A Rasch analysis. Journal of Huntingtons Disease, 4(4), 347–369.CrossRefGoogle ScholarPubMed
Nobis, L., & Husain, M. (2018). Apathy in Alzheimer's disease. Current Opinion in Behavioral Sciences, 22, 7–13.CrossRefGoogle ScholarPubMed
Nordin, S., Paulsen, J. S., & Murphy, C. (1995). Sensory- and memory-mediated olfactory dysfunction in Huntington's disease. Journal of the International Neuropsychology Society, 1(3), 281–290.CrossRefGoogle ScholarPubMed
Orth, M., Handley, O. J., Schwenke, C., Dunnett, S. B., Craufurd, D., Ho, A. K., & Investigators of the European Huntington's Disease, Network (2010). Observing Huntington's disease: The European Huntington's Disease Network's REGISTRY. PLoS Currents, 2, RRN1184..Google ScholarPubMed
Palminteri, S., Justo, D., Jauffret, C., Pavlicek, B., Dauta, A., Delmaire, C., & Pessiglione, M. (2012). Critical roles for anterior insula and dorsal striatum in punishment-based avoidance learning. Neuron, 76(5), 998–1009.CrossRefGoogle ScholarPubMed
Papoutsi, M., Labuschagne, I., Tabrizi, S. J., & Stout, J. C. (2014). The cognitive burden in Huntington's disease: Pathology, phenotype, and mechanisms of compensation. Movement Disorders, 29(5), 673–683.CrossRefGoogle ScholarPubMed
Paulsen, J. S., & Long, J. D. (2014). Onset of Huntington's disease: Can it be purely cognitive? Movement Disorders, 29(11), 1342–1350.CrossRefGoogle ScholarPubMed
Paulsen, J. S., Smith, M. M., Long, J. D., & Predict HD Investigators & Coordinators of the Huntington Study Group. (2013). Cognitive decline in prodromal Huntington disease: Implications for clinical trials. Journal of Neurology, Neurosurgery and Psychiatry, 84(11), 1233–1239.10.1136/jnnp-2013-305114CrossRefGoogle ScholarPubMed
Penney, J. B. Jr., Vonsattel, J. P., MacDonald, M. E., Gusella, J. F., & Myers, R. H. (1997). CAG Repeat number governs the development rate of pathology in Huntington's disease. Annals of Neurology, 41(5), 689–692.10.1002/ana.410410521CrossRefGoogle ScholarPubMed
Pirogovsky-Turk, E., Moore, R. C., Filoteo, J. V., Litvan, I., Song, D. D., Lessig, S. L., & Schiehser, D. M. (2017). Neuropsychiatric predictors of cognitive decline in Parkinson disease: A longitudinal study. American Journal of Geriatric Psychiatry, 25(3), 279–289.CrossRefGoogle ScholarPubMed
Radakovic, R., & Abrahams, S. (2014). Developing a new apathy measurement scale: Dimensional apathy scale. Psychiatry Research, 219(3), 658–663.CrossRefGoogle ScholarPubMed
Reedeker, N., Bouwens, J. A., van Duijn, E., Giltay, E. J., Roos, R. A. C., & van der Mast, R. C. (2011). Incidence, course, and predictors of apathy in Huntington's disease: A two-year prospective study. The Journal of Neuropsychiatry and Clinical Neurosciences, 23(4), 434–441.10.1176/jnp.23.4.jnp434CrossRefGoogle ScholarPubMed
Richard, E., Schmand, B., Eikelenboom, P., Yang, S. C., Ligthart, S. A., Moll van Charante, E. P., & Alzheimer's Disease Neuroimaging Investigators. (2012). Symptoms of apathy are associated with progression from mild cognitive impairment to Alzheimer's disease in non-depressed subjects. Dementia and Geriatric Cognnitive Disorders, 33(2-3), 204–209.CrossRefGoogle ScholarPubMed
Robert, P. H., Berr, C., Volteau, M., Bertogliati-Fileau, C., Benoit, M., Guerin, O., & PréAL Study Group, (2008). Importance of lack of interest in patients with mild cognitive impairment. American Journal of Geriatric Psychiatry, 16(9), 770–776.10.1097/JGP.0b013e31817e73dbCrossRefGoogle ScholarPubMed
Ross, C. A., Pantelyat, A., Kogan, J., & Brandt, J. (2014). Determinants of functional disability in Huntington's disease: Role of cognitive and motor dysfunction. Movement Disorders, 29(11), 1351–1358.10.1002/mds.26012CrossRefGoogle ScholarPubMed
Rubin, D. B. (1987). Multiple imputation for nonresponses in surveys. New York: Wiley.CrossRefGoogle Scholar
SAS Institute Inc. (2015). SAS/STAT 14.0. Cary, NC, USA.Google Scholar
Schab, F. R. (1991). Odor memory: Taking stock. Psychological Bulletin, 109(2), 242–251.CrossRefGoogle ScholarPubMed
Shoulson, I., & Fahn, S. (1979). Huntington's disease: Clinical care and evaluation. Neurology, 29(1), 1–3.CrossRefGoogle ScholarPubMed
Smith, M. M., Mills, J. A., Epping, E. A., Westervelt, H. J., Paulsen, J. S., & PREDICT-HD Investigators of the Huntington Study Group (2012). Depressive symptom severity is related to poorer cognitive performance in prodromal Huntington disease. Neuropsychology, 26(5), 664–669.CrossRefGoogle ScholarPubMed
Sousa, M., Moreira, F., Jesus-Ribeiro, J., Marques, I., Cunha, F., Canario, N., & Januario, C. (2018). Apathy profile in Parkinson's and Huntington's disease: A comparative cross-sectional study. European Neurology, 79(1–2), 13–20.CrossRefGoogle ScholarPubMed
Starkstein, S. E., Jorge, R., Mizrahi, R., & Robinson, R. G. (2006). A prospective longitudinal study of apathy in Alzheimer's disease. Journal of Neurology Neurosurgery and Psychiatry, 77(1), 8–11.CrossRefGoogle ScholarPubMed
Stout, J. C., Glikmann-Johnston, Y., & Andrews, S. C. (2016). Cognitive assessment strategies in Huntington's disease research. Journal of Neuroscience Methods, 265, 19–24.CrossRefGoogle ScholarPubMed
Stout, J. C., Jones, R., Labuschagne, I., O'Regan, A. M., Say, M. J., Dumas, E. M., & Frost, C. (2012). Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 83(7), 687–694.CrossRefGoogle ScholarPubMed
Stout, J. C., Paulsen, J. S., Queller, S., Solomon, A. C., Whitlock, K. B., Campbell, J. C., & Aylward, E. H. (2011). Neurocognitive signs in prodromal Huntington disease. Neuropsychology, 25(1), 1–14.CrossRefGoogle ScholarPubMed
Tabrizi, S. J., Langbehn, D. R., Leavitt, B. R., Roos, R. A., Durr, A., Craufurd, D., & Stout, J. C. (2009). Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: Cross-sectional analysis of baseline data. The Lancet. Neurology, 8(9), 791–801..CrossRefGoogle ScholarPubMed
Tabrizi, S. J., Scahill, R. I., Owen, G., Durr, A., Leavitt, B. R., Roos, R. A., & Track HD Investigators (2013). Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: Analysis of 36-month observational data. Lancet Neurology, 12(7), 637–649.CrossRefGoogle ScholarPubMed
Verhaeghen, P., & Salthouse, T. A. (1997). Meta-analyses of age-cognition relations in adulthood: Estimates of linear and nonlinear age effects and structural models. Psychological Bulletin, 122(3), 231–249.CrossRefGoogle ScholarPubMed
Walker, F. O. (2007). Huntington's disease. Lancet, 369, 218–228.10.1016/S0140-6736(07)60111-1CrossRefGoogle ScholarPubMed