Gray Matter Vulnerabilities Predict Longitudinal Development of Apathy in Huntington's Disease.
Huntington's disease
apathy
individual differences
longitudinal
neurodegeneration
structural MRI
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
15
04
2021
received:
20
11
2020
accepted:
16
04
2021
pubmed:
18
5
2021
medline:
14
10
2021
entrez:
17
5
2021
Statut:
ppublish
Résumé
Apathy, a common neuropsychiatric disturbance in Huntington's disease (HD), is subserved by a complex neurobiological network. However, no study has yet employed a whole-brain approach to examine underlying regional vulnerabilities that may precipitate apathy changes over time. To identify whole-brain gray matter volume (GMV) vulnerabilities that may predict longitudinal apathy development in HD. Forty-five HD individuals (31 female) were scanned and evaluated for apathy and other neuropsychiatric features using the short-Problem Behavior Assessment for a maximum total of six longitudinal visits (including baseline). In order to identify regions where changes in GMV may describe changes in apathy, we performed longitudinal voxel-based morphometry (VBM) on those 33 participants with a magnetic resonance imaging (MRI) scan on their second visit at 18 ± 6 months follow-up (78 MRI datasets). We next employed a generalized linear mixed-effects model (N = 45) to elucidate whether initial and specific GMV may predict apathy development over time. Utilizing longitudinal VBM, we revealed a relationship between increases in apathy and specific GMV atrophy in the right middle cingulate cortex (MCC). Furthermore, vulnerability in the right MCC volume at baseline successfully predicted the severity and progression of apathy over time. This study highlights that individual differences in apathy in HD may be explained by variability in atrophy and initial vulnerabilities in the right MCC, a region implicated in action-initiation. These findings thus serve to facilitate the prediction of an apathetic profile, permitting targeted, time-sensitive interventions in neurodegenerative disease with potential implications in otherwise healthy populations. © 2021 International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Apathy, a common neuropsychiatric disturbance in Huntington's disease (HD), is subserved by a complex neurobiological network. However, no study has yet employed a whole-brain approach to examine underlying regional vulnerabilities that may precipitate apathy changes over time.
OBJECTIVES
To identify whole-brain gray matter volume (GMV) vulnerabilities that may predict longitudinal apathy development in HD.
METHODS
Forty-five HD individuals (31 female) were scanned and evaluated for apathy and other neuropsychiatric features using the short-Problem Behavior Assessment for a maximum total of six longitudinal visits (including baseline). In order to identify regions where changes in GMV may describe changes in apathy, we performed longitudinal voxel-based morphometry (VBM) on those 33 participants with a magnetic resonance imaging (MRI) scan on their second visit at 18 ± 6 months follow-up (78 MRI datasets). We next employed a generalized linear mixed-effects model (N = 45) to elucidate whether initial and specific GMV may predict apathy development over time.
RESULTS
Utilizing longitudinal VBM, we revealed a relationship between increases in apathy and specific GMV atrophy in the right middle cingulate cortex (MCC). Furthermore, vulnerability in the right MCC volume at baseline successfully predicted the severity and progression of apathy over time.
CONCLUSIONS
This study highlights that individual differences in apathy in HD may be explained by variability in atrophy and initial vulnerabilities in the right MCC, a region implicated in action-initiation. These findings thus serve to facilitate the prediction of an apathetic profile, permitting targeted, time-sensitive interventions in neurodegenerative disease with potential implications in otherwise healthy populations. © 2021 International Parkinson and Movement Disorder Society.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2162-2172Informations de copyright
© 2021 International Parkinson and Movement Disorder Society.
Références
MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993;72(6):971-983.
Langbehn DR, Hayden M, Paulsen JS. CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches. Am J Med Genet Part B Neuropsychiatr Genet 2010;153B(2):397-408.
Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D, et al. Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 2009;8(9):791-801.
Waldvogel HJ, Kim EH, Tippett LJ, Vonsattel J-PG, Faull RL. The neuropathology of Huntington's disease. In: HHP N, Cenci MA, eds. Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease. Heidelberg: Springer; 2014:33-80. https://doi.org/10.1007/7854_2014_354. Accessed November 4, 2017.
Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA, et al. 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 Neurol 2013;12(7):637-649.
Camacho M, Barker RA, Mason SL. Apathy in Huntington's disease: a review of the current conceptualization. J Alzheimer's Dis Park 2018;08(02):431.
Chase TN. Apathy in neuropsychiatric disease: diagnosis, pathophysiology, and treatment. Neurotox Res 2011;19(2):266-278.
Paoli R, Botturi A, Ciammola A, Silani V, Prunas C, Lucchiari C, et al. Neuropsychiatric burden in Huntington's disease. Brain Sci 2017;7(6):67.
Thompson J, Harris J, Sollom A, Stopford C, Howard E, Snowden J, et al. Longitudinal evaluation of neuropsychiatric symptoms in Huntington's disease. J Neuropsychiatry Clin Neurosci 2012;24:53-60.
Naarding P, Janzing JG, Eling P, van der Werf S, Kremer B. Apathy is not depression in Huntington's disease. J Neuropsychiatry Clin Neurosci 2009;21(3):266-270.
Kingma EM, van Duijn E, Timman R, van der Mast RC, Roos RAC. Behavioural problems in Huntington's disease using the problem behaviours assessment. Gen Hosp Psychiatry 2008;30(2):155-161.
Thompson JC, Snowden JS, Craufurd D, Neary D. Behavior in Huntington's disease: dissociating cognition-based and mood-based changes. J Neuropsychiatry Clin Neurosci 2002;14(1):37-43.
van Duijn E, Craufurd D, Hubers AAM, Giltay EJ, Bonelli R, Rickards H, et al. Neuropsychiatric symptoms in a European Huntington's disease cohort (REGISTRY). J Neurol Neurosurg Psychiatry 2014;85(12):1411-1418.
Baake V, Coppen EM, van Duijn E, Dumas EM, van den Bogaard SJA, Scahill RI, et al. Apathy and atrophy of subcortical brain structures in Huntington's disease: a two-year follow-up study. Neuroimage Clin 2018;19:66-70.
van Duijn E, Reedeker N, Giltay EJ, Eindhoven D, Roos RAC, van der Mast RC. Course of irritability, depression and apathy in Huntington's disease in relation to motor symptoms during a two-year follow-up period. Neurodegener Dis 2013;13(1):9-16. https://www.karger.com/Article/FullText/343210. Accessed May 3, 2019.
Mason S, Barker RA. Rating apathy in Huntington's disease: patients and companions agree. J Huntingtons Dis 2015;4:49-59.
Martinez-Horta S, Perez-Perez J, Sampedro F, Pagonabarraga J, Horta-Barba A, Carceller-Sindreu M, et al. Structural and metabolic brain correlates of apathy in Huntington's disease: apathy in Huntington's disease. Mov Disord 2018;33(7):1151-1159.
McColgan P, Razi A, Gregory S, Seunarine KK, Durr A, et al. Structural and functional brain network correlates of depressive symptoms in premanifest Huntington's disease: depressive symptoms in preHD. Hum Brain Mapp 2017;38(6):2819-2829.
Delmaire C, Dumas EM, Sharman MA, van den Bogaard SJA, Valabregue R, Jauffret C, et al. The structural correlates of functional deficits in early Huntington's disease: structural correlates of functional deficits in HD. Hum Brain Mapp 2013;34(9):2141-2153.
De Paepe AE, Sierpowska J, Garcia-Gorro C, Martinez-Horta S, Perez-Perez J, Kulisevsky J, et al. White matter cortico-striatal tracts predict apathy subtypes in Huntington's disease. Neuroimage Clin. 2019;24:101965.
Reedeker N, Bouwens J, van Duijn E, Giltay EJ, Roos RAC, van der Mast RC. Incidence, course, and predictors of apathy in Huntington's disease: a two-year prospective study. J Neuropsychiatry Clin Neurosci 2011;23(4):434.
Garcia-Gorro C, Llera A, Martinez-Horta S, Perez-Perez J, Kulisevsky J, Rodriguez-Dechicha N, et al. Specific patterns of brain alterations underlie distinct clinical profiles in Huntington's disease. Neuroimage Clin. 2019;23:101900.
Callaghan J, Stopford C, Arran N, Boisse M-F, Coleman A, Santos RD, et al. Reliability and factor structure of the short problem behaviors assessment for Huntington's disease (PBA-s) in the TRACK-HD and REGISTRY studies. J Neuropsychiatry Clin Neurosci 2015;27(1):59-64.
Martinez-Horta S, Perez-Perez J, van Duijn E, Fernandez-Bobadilla R, Carceller M, Pagonabarraga J, et al. Neuropsychiatric symptoms are very common in premanifest and early stage Huntington's disease. Parkinsonism Relat Disord 2016;30:58-64.
Craufurd D, Thompson JC, Snowden JS. Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol 2001;14(4):219-226.
Huntington Study Group. Unified Huntington's disease rating scale: reliability and consistency. Mov Disord 1996;11(2):136-142.
Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol 2014;10(4):204-216.
Mechelli A, Friston KJ, Frackowiak RS, Price CJ. Structural covariance in the human cortex. J Neurosci 2005;25(36):8303-8310.
Ashburner J. VBM Tutorial; 2010. http://www.fil.ion.ucl.ac.uk/~john/misc/VBMclass10.pdf
James CE, Oechslin MS, Van De Ville D, Hauert C-A, Descloux C, Lazeyras F. Musical training intensity yields opposite effects on grey matter density in cognitive versus sensorimotor networks. Brain Struct Funct 2014;219(1):353-366.
Gibbons RD, Hedeker D, DuToit S. Advances in analysis of longitudinal data. Annu Rev Clin Psychol 2010;6:79-107.
Bonner-Jackson A, Long JD, Westervelt H, Tremont G, Aylward E, Paulsen JS, et al. Cognitive reserve and brain reserve in prodromal Huntington's disease. J Int Neuropsychol Soc 2013;19(07):739-750.
Odish OFF, Leemans A, Reijntjes RHAM, van den Bogaard SJA, Dumas EM, Wolterbeek R, et al. Microstructural brain abnormalities in Huntington's disease: a two-year follow-up: microstructural brain abnormalities in HD. Hum Brain Mapp 2015;36(6):2061-2074.
Harrington DL, Long JD, Durgerian S, Mourany L, Koenig K, Bonner-Jackson A, et al. Cross-sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease: structure imaging in prodromal HD. Mov Disord 2016;31(11):1664-1675.
de Diego-Balaguer R, Schramm C, Rebeix I, Dupoux E, Durr A, Brice A, et al. COMT Val158Met polymorphism modulates Huntington's disease progression. PLoS One 2016;11(9):e0161106.
Becker RA, Chambers JM. Wilks AR. Monterey, CA: Wadsworth & Brooks/Cole: The New S Language; 1988.
Lüdecke D, Makowski D, Waggoner P. Performance: assessment of regression models performance; 2019. https://easystats.github.io/performance/
Burnham K, Anderson D. Model Selection and Multimodal Inference. New York, NY: Springer; 2002.
Long J. Data Analysis for Behavioral Sciences Using R. Thousand Oaks, CA: Sage Publications Inc.; 2011.
Brooks ME, Kristensen K, Benthem KJ, van Magnusson A, Berg CW, Nielsen A, et al. glmmTMB balances speed and flexibility among packages for zero-inflated generalized linear mixed modeling. R J 2017;9(2):378-400.
Gignac GE, Szodorai ET. Effect size guidelines for individual differences researchers. Personal Individ Differ 2016;102:74-78.
Vogt BA. Midcingulate cortex: structure, connections, homologies, functions and diseases. J Chem Neuroanat 2016;74:28-46.
Mega MS, Cummings JL, Salloway S, Malloy P. The limbic system: an anatomic, phylogenetic, and clinical perspective. J Neuropsychiatry Clin Neurosci 1997;9(3):315-330.
Allman JM, Hakeem A, Erwin JM, Nimchinsky E, Hof P. The anterior cingulate cortex: the evolution of an interface between emotion and cognition. Ann N Y Acad Sci 2006;935(1):107-117.
Theleritis C, Politis A, Siarkos K, Lyketsos CG. A review of neuroimaging findings of apathy in Alzheimer's disease. Int Psychogeriatr 2014;26(2):195-207.
Kos C, van Tol M-J, Marsman J-BC, Knegtering H, Aleman A. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders. Neurosci Biobehav Rev 2016;69:381-401.
Le Heron C, Apps MAJ, Husain M. The anatomy of apathy: a neurocognitive framework for amotivated behaviour. Neuropsychologia 2018;118:54-67.
Lavretsky H, Zheng L, Weiner MW, Mungas D, Reed B, Kramer JH, et al. The MRI brain correlates of depressed mood, anhedonia, apathy, and anergia in older adults with and without cognitive impairment or dementia. Int J Geriatr Psychiatry 2008;23(10):1040-1050.
Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex 2006;16(7):916-928.
Bonelli RM, Cummings JL. Frontal-subcortical circuitry and behavior. Dialogues Clin Neurosci 2007;9(2):141.
Guimarães HC, Levy R, Teixeira AL, Beato RG, Caramelli P. Neurobiology of apathy in Alzheimer's disease. Arq Neuropsiquiatr 2008;66(2b):436-443.
Robert PH, Mulin E, Malléa P, David R. REVIEW: apathy diagnosis, assessment, and treatment in Alzheimer's disease. CNS Neurosci Ther 2010;16(5):263-271.
Misiura MB, Ciarochi J, Vaidya J, Bockholt J, Johnson HJ, Calhoun VD, et al. Apathy is related to cognitive control and striatum volumes in prodromal Huntington's disease. J Int Neuropsychol Soc 2019;26:1-8.
Pagonabarraga J, Kulisevsky J, Strafella AP, Krack P. Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment. Lancet Neurol 2015;14(5):518-531.
Moretti R, Signori R. Neural correlates for apathy: frontal-prefrontal and parietal cortical-subcortical circuits. Front Aging Neurosci 2016;8:289. http://journal.frontiersin.org/article/10.3389/fnagi.2016.00289/full. Accessed December 3, 2018.
Onoda K, Yamaguchi S. Dissociative contributions of the anterior cingulate cortex to apathy and depression: topological evidence from resting-state functional MRI. Neuropsychologia 2015;77:10-18.
Bonnelle V, Manohar S, Behrens T, Husain M. Individual differences in premotor brain systems underlie behavioral apathy. Cereb Cortex. 2016;bhv247.
Siegel JS, Snyder AZ, Metcalf NV, Fucetola RP, Hacker CD, Shimony JS, et al. The circuitry of abulia: insights from functional connectivity MRI. Neuroimage Clin. 2014;6:320-326.
Massimo L, Powers C, Moore P, Vesely L, Avants B, Gee J, et al. Neuroanatomy of apathy and disinhibition in frontotemporal lobar degeneration. Dement Geriatr Cogn Disord 2009;27(1):96-104.
Reijnders JSAM, Scholtissen B, Weber WEJ, Aalten P, Verhey FRJ, Leentjens AFG. Neuroanatomical correlates of apathy in Parkinson's disease: a magnetic resonance imaging study using voxel-based morphometry. Mov Disord Off J Mov Disord Soc 2010;25(14):2318-2325.
Apostolova LG, Akopyan GG, Partiali N, Steiner CA, Dutton RA, Hayashi KM, et al. Structural correlates of apathy in Alzheimer's disease. Dement Geriatr Cogn Disord 2007;24(2):91-97.
Bruen PD, McGeown WJ, Shanks MF, Venneri A. Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer's disease. Brain J Neurol 2008;131(pt 9):2455-2463.
Stevens FL. Anterior cingulate cortex: unique role in cognition and emotion. J Neuropsychiatry Clin Neurosci 2011;23(2):121-125.
Beckmann M, Johansen-Berg H, Rushworth MFS. Connectivity-based parcellation of human cingulate cortex and its relation to functional specialization. J Neurosci 2009;29(4):1175-1190.
Koolschijn PCMP, van Haren NEM, Lensvelt-Mulders GJLM, Pol HEH, Kahn RS. Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 2009;30(11):3719-3735.
Rushworth MFS, Behrens TEJ, Rudebeck PH, Walton ME. Contrasting roles for cingulate and orbitofrontal cortex in decisions and social behaviour. Trends Cogn Sci 2007;11(4):168-176.
Kurniawan IT, Guitart-Masip M, Dolan RJ. Dopamine and effort-based decision making. Front Neurosci 2011;5(81):1-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122071/. Accessed May 14, 2019.
Le Heron C, Manohar S, Plant O, Muhammed K, Griffanti L, Nemeth A, et al. Dysfunctional effort-based decision-making underlies apathy in genetic cerebral small vessel disease. Brain 2018;141(11):3193-3210. https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awy257/5139779. Accessed October 26, 2018.
Eddy CM, Parkinson EG, Rickards HE. Changes in mental state and behaviour in Huntington's disease. Lancet Psychiatry 2016;3(11):1079-1086.
Vinther-Jensen T, Larsen IU, Hjermind LE, Budtz-Jørgensen E, Nielsen TT, Nørremølle A, et al. A clinical classification acknowledging neuropsychiatric and cognitive impairment in Huntington's disease. Orphanet J Rare Dis 2014;9(1):114.
Duff K, Paulsen JS, Beglinger LJ, Langbehn DR, Stout JC. Psychiatric symptoms in Huntington's disease before diagnosis: the predict-HD study. Biol Psychiatry 2007;62(12):1341-1346.
Zgaljardic DJ, Borod JC, Foldi NS, Rocco M, Mattis PJ, Gordon MF, et al. Relationship between self-reported apathy and executive dysfunction in nondemented patients with Parkinson disease. Cogn Behav Neurol 2007;20(3):184-192.
Varanese S, Perfetti B, Ghilardi MF, Di Rocco A. Apathy, but not depression, reflects inefficient cognitive strategies in Parkinson's disease. PLoS One 2011;6(3):e17846.
Sinha N, Manohar S, Husain M. Impulsivity and apathy in Parkinson's disease. J Neuropsychol 2013;7(2):255-283.
Meyer A, Zimmermann R, Gschwandtner U, Hatz F, Bousleiman H, Schwarz N, et al. Apathy in Parkinson's disease is related to executive function, gender and age but not to depression. Front Aging Neurosci 2015;6(350):1-6. http://journal.frontiersin.org/article/10.3389/fnagi.2014.00350/abstract. Accessed February 6, 2019.
Kawagoe T, Onoda K, Yamaguchi S. Apathy and executive function in healthy elderly-resting state fMRI study. Front Aging Neurosci 2017;9:124.
Andrews SC, Langbehn DR, Craufurd D, Durr A, Leavitt BR, Roos RA, et al. Apathy predicts rate of cognitive decline over 24 months in premanifest Huntington's disease. Psychol Med 2020;17:1-7.
Leh SE, Petrides M, Strafella AP. The neural circuitry of executive functions in healthy subjects and Parkinson's disease. Neuropsychopharmacology 2010;35(1):70-85.
McArdle JJ, Hamgami F, Jones K, Jolesz F, Kikinis R, Spiro A, et al. Structural modeling of dynamic changes in memory and brain structure using longitudinal data from the normative aging study. J Gerontol B Psychol Sci Soc Sci 2004;59(6):P294-P304.
Grimm KJ, An Y, McArdle JJ, Zonderman AB, Resnick SM. Recent changes leading to subsequent changes: extensions of multivariate latent difference score models. Struct Equ Model Multidiscip J 2012;19(2):268-292.
Cercignani M, Bouyagoub S. Brain microstructure by multi-modal MRI: is the whole greater than the sum of its parts? Neuroimage 2018;182:117-127.
Toh EA, MacAskill MR, Dalrymple-Alford JC, Myall DJ, Livingston L, Macleod SA, et al. Comparison of cognitive and UHDRS measures in monitoring disease progression in Huntington's disease: a 12-month longitudinal study. Transl Neurodegener 2014;3:15.