Hostname: page-component-7479d7b7d-t6hkb Total loading time: 0 Render date: 2024-07-15T14:10:12.377Z Has data issue: false hasContentIssue false
  • English
  • Français

Apathy is associated with white matter network disruption and specific cognitive deficits in Parkinson's disease

Published online by Cambridge University Press:  11 June 2020

Ming-Ching Wen Open the ORCID record for Ming-Ching Wen [Opens in a new window] ,
Alexandre Thiery ,
Wen-Yih Isaac Tseng ,
Trina Kok ,
Zheyu Xu ,
Shu Ting Chua  and
Louis C.S. Tan
Ming-Ching Wen*
Affiliation:
Department of Research, National Neuroscience Institute, Singapore Duke-NUS Medical School, Singapore
Alexandre Thiery
Affiliation:
Department of Statistics and Applied Probability, National University of Singapore, Singapore
Wen-Yih Isaac Tseng
Affiliation:
Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan
Trina Kok
Affiliation:
Clinical Imaging Research Centre, National University of Singapore, Singapore
Zheyu Xu
Affiliation:
Department of Neurology, National Neuroscience Institute, Singapore
Shu Ting Chua
Affiliation:
Department of Neurology, National Neuroscience Institute, Singapore
Louis C.S. Tan
Affiliation:
Department of Research, National Neuroscience Institute, Singapore Duke-NUS Medical School, Singapore Department of Neurology, National Neuroscience Institute, Singapore
*
Author for correspondence: Ming-Ching Wen, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Apathy is common in Parkinson's disease (PD) but its underlying white matter (WM) architecture is not well understood. Moreover, how apathy affects cognitive functions in PD remains unclear. We investigated apathy-related WM network alterations and the impact of apathy on cognition in the context of PD.

Methods

Apathetic PD patients (aPD), non-apathetic PD patients (naPD), and matched healthy controls (HCs) underwent brain scans and clinical assessment. Graph-theoretical and network-based analyses were used for group comparisons of WM features derived from diffusion spectrum imaging (DSI). Path analysis was used to determine the direct and indirect effects of apathy and other correlates on different cognitive functions.

Results

The aPD group was impaired on neural integration measured by global efficiency (p = 0.009) and characteristic path length (p = 0.04), executive function (p < 0.001), episodic memory (p < 0.001) and visuospatial ability (p = 0.02), and had reduced connectivity between the bilateral parietal lobes and between the putamen and temporal regions (p < 0.05). In PD, executive function was directly impacted by apathy and motor severity and indirectly influenced by depression; episodic memory was directly and indirectly impacted by apathy and depression, respectively; conversely, visuospatial ability was not related to any of these factors. Neural integration, though being marginally correlated with apathy, was not associated with cognition.

Conclusions

Our results suggest compromised neural integration and reduced structural connectivity in aPD. Apathy, depression, and motor severity showed distinct impacts on different cognitive functions with apathy being the most influential determinant of cognition in PD.

Keywords

Apathycognitiondiffusion spectrum imaginggraph theorymotor severity
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 2 , January 2022 , pp. 264 - 273
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

*

Senior author.

References

Baglio, F., Blasi, V., Falini, A., Farina, E., Mantovani, F., Olivotto, F., … Bozzali, M. (2011). Functional brain changes in early Parkinson's disease during motor response and motor inhibition. Neurobiology of Aging, 32, 115–124.CrossRefGoogle ScholarPubMed
Butterfield, L. C., Cimino, C. R., Oelke, L. E., Hauser, R. A., & Sanchez-Ramos, J. (2010). The independent influence of apathy and depression on cognitive functioning in Parkinson's disease. Neuropsychology, 24, 721–730.CrossRefGoogle ScholarPubMed
Carriere, N., Besson, P., Dujardin, K., Duhamel, A., Defebvre, L., Delmaire, C., & Devos, D. (2014). Apathy in Parkinson's disease is associated with nucleus accumbens atrophy: A magnetic resonance imaging shape analysis. Movement Disorders, 29, 897–903.CrossRefGoogle ScholarPubMed
Cheung, R. W., Cheung, M. C., & Chan, A. S. (2004). Confrontation naming in Chinese patients with left, right or bilateral brain damage. Journal of International Neuropsychological Society, 10, 46–53.CrossRefGoogle ScholarPubMed
Cohen, J. R., & D'Esposito, M. (2016). The segregation and integration of distinct brain networks and their relationship to cognition. Journal of Neuroscience, 36, 12083–12094.CrossRefGoogle ScholarPubMed
Dalrymple-Alford, J. C., MacAskill, M. R., Nakas, C. T., Livingston, L., Graham, C., Crucian, G. P., … Anderson, T. J. (2010). The MoCA: Well-suited screen for cognitive impairment in Parkinson disease. Neurology, 75, 1717–1725.CrossRefGoogle ScholarPubMed
D'Elia, L. F., Satz, P., Uchiyama, C. L., & White, T. (1996). Color trails test. Odessa, FL: PAR.Google Scholar
den Brok, M. G., van Dalen, J. W., van Gool, W. A., Moll van Charante, E. P., de Bie, R. M., & Richard, E. (2015). Apathy in Parkinson's disease: A systematic review and meta-analysis. Movement Disorders, 30, 759–769.CrossRefGoogle ScholarPubMed
Destrieux, C., Fischl, B., Dale, A., & Halgren, E. (2010). Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature. Neuroimage, 53, 1–15.CrossRefGoogle ScholarPubMed
D'Iorio, A., Maggi, G., Vitale, C., Trojano, L., & Santangelo, G. (2018). “Pure apathy” and cognitive dysfunctions in Parkinson's disease: A meta-analytic study. Neuroscience & Biobehavioral Reviews, 94, 1–10.CrossRefGoogle ScholarPubMed
Drijgers, R. L., Dujardin, K., Reijnders, J. S., Defebvre, L., & Leentjens, A. F. (2010). Validation of diagnostic criteria for apathy in Parkinson's disease. Parkinsonism & Related Disorders, 16, 656–660.CrossRefGoogle ScholarPubMed
Dubois, B., Slachevsky, A., Litvan, I., & Pillon, B. (2000). The FAB: A frontal assessment battery at bedside. Neurology, 55, 1621–1626.CrossRefGoogle ScholarPubMed
Goetz, C. G., Fahn, S., Martinez-Martin, P., Poewe, W., Sampaio, C., Stebbins, G. T., … LaPelle, N. (2007). Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan. Movement Disorders, 22, 41–47.CrossRefGoogle ScholarPubMed
Goodglass, H., & Kaplan, E. F. (1993). The Boston diagnostic aphasia examination. Philadelphia: Lea and Febiger.Google Scholar
Hollocks, M. J., Lawrence, A. J., Brookes, R. L., Barrick, T. R., Morris, R. G., Husain, M., & Markus, H. S. (2015). Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes. Brain, 138, 3803–3815.CrossRefGoogle ScholarPubMed
Kos, C., van Tol, M. J., Marsman, J. B., Knegtering, H., & Aleman, A. (2016). Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders. Neuroscience & Biobehavioral Reviews, 69, 381–401.CrossRefGoogle ScholarPubMed
Latora, V., & Marchiori, M. (2003). Economic small-world behavior in weighted networks. European Physical Journal B—Condensed Matter and Complex Systems, 32, 249–263.CrossRefGoogle Scholar
Le Heron, C., Holroyd, C. B., Salamone, J., & Husain, M. (2019). Brain mechanisms underlying apathy. Journal of Neurology Neurosurgery & Psychiatry, 90, 302–312.CrossRefGoogle ScholarPubMed
Levy, R., & Dubois, B. (2006). Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cerebral Cortex, 16, 916–928.CrossRefGoogle ScholarPubMed
Litvan, I., Goldman, J. G., Tröster, A. I., Schmand, B. A., Weintraub, D., Petersen, R. C., … Emre, M., (2012). Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Movement Disorders, 27, 349–356.CrossRefGoogle ScholarPubMed
Lleras, C. (2005). Path analysis. Encyclopedia of Social Measurement, 3(1), 25–30.CrossRefGoogle Scholar
Lucas-Jimenez, O., Ojeda, N., Pena, J., Cabrera-Zubizarreta, A., Diez-Cirarda, M., Gomez-Esteban, J. C., … Ibarretxe-Bilbao, N. (2018). Apathy and brain alterations in Parkinson's disease: A multimodal imaging study. Annals of Clinical and Translational Neurology, 5, 803–814.CrossRefGoogle ScholarPubMed
Malone, I. B., Leung, K. K., Clegg, S., Barnes, J., Whitwell, J. L., Ashburner, J., … Ridgway, G. R. (2014). Accurate automatic estimation of total intracranial volume: A nuisance variable with less nuisance. Neuroimage, 104, 366–372.CrossRefGoogle ScholarPubMed
Marc, L. G., Raue, P. J., & Bruce, M. L. (2008). Screening performance of the 15-item geriatric depression scale in a diverse elderly home care population. American Journal of Geriatric Psychiatry, 16, 914–921.CrossRefGoogle Scholar
Mitchell, J., Mathews, H. F., & Yesavage, J. A. (1993). A multidimensional examination of depression among the elderly. Research on Aging, 15, 198–219.CrossRefGoogle Scholar
Mohs, R. C., Knopman, D., Petersen, R. C., Ferris, S. H., Ernesto, C., Grundman, M., … Thal, L. J. (1997). Development of cognitive instruments for use in clinical trials of antidementia drugs: Additions to the Alzheimer's Disease Assessment Scale that broaden its scope. Alzheimer Disease and Associated Disorders, 11, S13–S21.CrossRefGoogle Scholar
Moretti, R., & Signori, R. (2016). Neural correlates for apathy: Frontal-prefrontal and parietal cortical-subcortical circuits. Frontiers in Aging Neuroscience, 8, 289.CrossRefGoogle ScholarPubMed
Nodel, M., Yakhno, N., Medvedeva, A., & Kulikov, M. (2014). Apathy in Parkinson disease. Frontiers in Biology, 9, 324–331.CrossRefGoogle Scholar
Raimo, S., Santangelo, G., D'Iorio, A., Trojano, L., & Grossi, D. (2019). Neural correlates of apathy in patients with neurodegenerative disorders: An activation likelihood estimation (ALE) meta-analysis. Brain Imaging and Behavior, 13, 1815–1834.CrossRefGoogle ScholarPubMed
Robbins, T. W., & Cools, R. (2014). Cognitive deficits in Parkinson's disease: A cognitive neuroscience perspective. Movement Disorders, 29, 597–607.CrossRefGoogle ScholarPubMed
Rubinov, M., & Sporns, O. (2010). Complex network measures of brain connectivity: Uses and interpretations. Neuroimage, 52, 1059–1069.CrossRefGoogle ScholarPubMed
Schrag, A., Siddiqui, U. F., Anastasiou, Z., Weintraub, D., & Schott, J. M. (2017). Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson's disease: A cohort study. Lancet Neurology, 16, 66–75.CrossRefGoogle ScholarPubMed
Sheehan, D. V., Lecrubier, Y., Harnett Sheehan, K., Janavs, J., Weiller, E., Keskiner, A., … CDunbar, G. (1997). The validity of the Mini International Neuropsychiatric Interview (MINI) according to the SCID-P and its reliability. European Psychiatry, 12, 232–241.CrossRefGoogle Scholar
Starkstein, S. E., Mayberg, H. S., Preziosi, T. J., Andrezejewski, P., Leiguarda, R., & Robinson, R. G. (1992). Reliability, validity, and clinical correlates of apathy in Parkinson's disease. Journal of Neuropsychiatry and Clinical Neurosciences, 4, 134–139.Google ScholarPubMed
Sunderland, T., Hill, J. L., Mellow, A. M., Lawlor, B. A., Gundersheimer, J., Newhouse, P. A., & Grafman, J. H. (1989). Clock drawing in Alzheimer's disease. A novel measure of dementia severity. Journal of the American Geriatrics Society, 37, 725–729.CrossRefGoogle ScholarPubMed
Tay, J., Tuladhar, A. M., Hollocks, M. J., Brookes, R. L., Tozer, D. J., Barrick, T. R., … Markus, H. S. (2019). Apathy is associated with large-scale white matter network disruption in small vessel disease. Neurology, 92, e1157–e1167.Google ScholarPubMed
Tomlinson, C. L., Stowe, R., Patel, S., Rick, C., Gray, R., & Clarke, C. E. (2010). Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Movement Disorders, 25, 2649–2653.CrossRefGoogle ScholarPubMed
Tuladhar, A. M., van Dijk, E., Zwiers, M. P., van Norden, A. G., de Laat, K. F., Shumskaya, E., … de Leeuw, F. E. (2016). Structural network connectivity and cognition in cerebral small vessel disease. Human Brain Mapping, 37, 300–310.CrossRefGoogle ScholarPubMed
van Dalen, J. W., van Wanrooij, L. L., Moll van Charante, E. P., Brayne, C., van Gool, W. A., & Richard, E. (2018). Association of Apathy with risk of incident dementia: A systematic review and meta-analysis. JAMA Psychiatry, 75, 1012–1021.CrossRefGoogle ScholarPubMed
Varanese, S., Perfetti, B., Ghilardi, M. F., & Di Rocco, A. (2011). Apathy, but not depression, reflects inefficient cognitive strategies in Parkinson's disease. PLoS One, 6, e17846.CrossRefGoogle Scholar
Wechsler, D. (1997). WAIS-III administration and scoring manual. San Antonio, TX: The Psychological Corporation.Google Scholar
Wechsler, D. (2009). Wechsler memory scale (4th ed.). San Antonio, TX: Pearson.Google Scholar
Wedeen, V. J., Hagmann, P., Tseng, W. Y., Reese, T. G., & Weisskoff, R. M. (2005). Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging. Magnetic Resonance in Medicine, 54, 1377–1386.CrossRefGoogle ScholarPubMed
Wedeen, V. J., Wang, R. P., Schmahmann, J. D., Benner, T., Tseng, W. Y., Dai, G., … de Crespigny, A. J. (2008). Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers. Neuroimage, 4, 1267–1277.CrossRefGoogle Scholar
Wen, M.-C., Chan, L. L., Tan, L. C., & Tan, E. K. (2016). Depression, anxiety, and apathy in Parkinson's disease: Insights from neuroimaging studies. European Journal of Neurology, 23, 1001–1019.CrossRefGoogle ScholarPubMed
Yeh, F., & Tseng, W. (2011). NTU-90: A high angular resolution brain atlas constructed by q-space diffeomorphic reconstruction. Neuroimage, 58, 91–99.CrossRefGoogle ScholarPubMed
Yesavage, J. A., Brink, T. L., Rose, T. L., Lum, O., Huang, V., Adey, M. B., & Leirer, V. O. (1983). Development and validation of a geriatric depression screening scale: A preliminary report. Journal of Psychiatric Research, 17, 37–49.CrossRefGoogle Scholar
Zalesky, A., Fornito, A., & Bullmore, E. (2010). Network-based statistic: Identifying differences in brain networks. Neuroimage, 53, 1197–1207.CrossRefGoogle ScholarPubMed
Zhao, H., He, J., Yi, J., & Yao, S. (2019). Factor structure and measurement invariance across gender groups of the 15-item geriatric depression scale among Chinese elders. Frontiers in Psychology, 10, 1360.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Wen et al. supplementary material

Figure S1

Download Wen et al. supplementary material(PDF)
PDF 448 KB