{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:31:20Z","timestamp":1790767880882,"version":"4.1.0"},"reference-count":185,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T00:00:00Z","timestamp":1686355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson\u2019s disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.<\/jats:p>","DOI":"10.3390\/cells12121599","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T01:28:21Z","timestamp":1686533301000},"page":"1599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Apathy in Parkinson\u2019s Disease: Clinical Patterns and Neurobiological Basis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0769-0289","authenticated-orcid":false,"given":"Matthieu","family":"B\u00e9reau","sequence":"first","affiliation":[{"name":"D\u00e9partement de Neurologie, CHU de Besan\u00e7on, 25000 Besan\u00e7on, France"},{"name":"Universit\u00e9 de Franche-Comt\u00e9, LINC Laboratoire de Recherches Int\u00e9gratives en Neurosciences et Psychologie Cognitive, 25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0568-7836","authenticated-orcid":false,"given":"Vincent","family":"Van Waes","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Franche-Comt\u00e9, LINC Laboratoire de Recherches Int\u00e9gratives en Neurosciences et Psychologie Cognitive, 25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Servant","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Franche-Comt\u00e9, LINC Laboratoire de Recherches Int\u00e9gratives en Neurosciences et Psychologie Cognitive, 25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloi","family":"Magnin","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Neurologie, CHU de Besan\u00e7on, 25000 Besan\u00e7on, France"},{"name":"Universit\u00e9 de Franche-Comt\u00e9, LINC Laboratoire de Recherches Int\u00e9gratives en Neurosciences et Psychologie Cognitive, 25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Tatu","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Neurologie, CHU de Besan\u00e7on, 25000 Besan\u00e7on, France"},{"name":"Universit\u00e9 de Franche-Comt\u00e9, LINC Laboratoire de Recherches Int\u00e9gratives en Neurosciences et Psychologie Cognitive, 25000 Besan\u00e7on, France"},{"name":"Laboratoire d\u2019Anatomie, Universit\u00e9 de Franche-Comt\u00e9, 25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Anheim","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Neurologie, CHU de Strasbourg, 67200 Strasbourg, France"},{"name":"F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg (FMTS), Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"},{"name":"Institut de g\u00e9n\u00e9tique Et de Biologie Mol\u00e9culaire Et Cellulaire (IGBMC), INSERM-U964, CNRS-UMR7104, Universit\u00e9 de Strasbourg, 67400 Illkirch-Graffenstaden, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1002\/mds.23664","article-title":"Parkinson\u2019s disease: The quintessential neuropsychiatric disorder","volume":"26","author":"Weintraub","year":"2011","journal-title":"Mov. 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