{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T20:46:43Z","timestamp":1781297203920,"version":"3.54.1"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":354,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014041","name":"Alzheimer\u2019s Disease Neuroimaging Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG024904"],"award-info":[{"award-number":["U01 AG024904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-12-2-0012"],"award-info":[{"award-number":["W81XWH-12-2-0012"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The brain-age gap, i.e. the difference between the brain age estimated from structural MRI data and the chronological age of an individual, has been proposed as a summary measure of brain integrity in neurodegenerative diseases. Here, we aimed to determine the brain-age gap in genetic and idiopathic Parkinson's disease and its association with surrogate markers of Alzheimer's disease and Parkinson's disease pathology and with rates of cognitive and motor function decline. We studied 1200 cases from the Parkinson's Progression Markers Initiative cohort, including idiopathic Parkinson's disease, asymptomatic and clinical mutation carriers in the leucine-rich repeat kinase 2 gene (LRRK2) and the glucocerebrosidase gene (GBA), and normal controls using a cohort study design. For comparison, we studied 187 Alzheimer's disease dementia cases and 254 controls from the Alzheimer's Disease Neuroimaging Initiative cohort. We used Bayesian ANOVA to determine associations of the brain-age gap with diagnosis, and baseline measures of motor and cognitive function, dopamine transporter activity and CSF markers of Alzheimer's disease type amyloid-\u03b242 and phosphotau pathology. Associations of brain-age gap with rates of cognitive and motor function decline were determined using Bayesian generalized mixed effect models. The brain-age gap in idiopathic Parkinson's disease patients was 0.7 years compared to controls, but 5.9 years in Alzheimer's disease dementia cases. In contrast, asymptomatic LRRK2 individuals had a 1.1. year younger brain age than controls. Across all cases, the brain-age gap was associated with motor impairment and (in the clinically manifest PD cases) reduced dopamine transporter activity, but less with CSF amyloid-\u03b242 and phosphotau. In idiopathic Parkinson's disease cases, however, the brain-age gap was associated with lower CSF amyloid-\u03b242 levels. In sporadic and genetic Parkinson's disease cases, a higher brain-age gap was associated with faster decline in episodic memory, and executive and motor function, whereas in asymptomatic LRRK2 cases, a smaller brain-age gap was associated with faster cognitive decline. In conclusion, brain age was sensitive to Alzheimer's disease like rather than Parkinson's disease like brain atrophy. Once an individual had idiopathic Parkinson's disease, their brain age was associated with markers of Alzheimer's disease rather than Parkinson's disease. Asymptomatic LRRK2 cases had seemingly younger brains than controls, and in these cases, younger brain age was associated with poorer cognitive outcome. This suggests that the term brain age is misleading when applied to disease stages where reactive brain changes with apparent volume increases rather than atrophy may drive the calculation of the brain age.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae382","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T16:21:41Z","timestamp":1734711701000},"source":"Crossref","is-referenced-by-count":13,"title":["Brain age in genetic and idiopathic Parkinson's disease"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-3194","authenticated-orcid":false,"given":"Stefan J","family":"Teipel","sequence":"first","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , Rostock 18147 ,","place":["Germany"]},{"name":"Department of Psychosomatic Medicine, University Medical Center Rostock , Rostock 18147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauke","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, University Medical Center Rostock , Rostock 18147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-9216","authenticated-orcid":false,"given":"Alexander","family":"Storch","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , Rostock 18147 ,","place":["Germany"]},{"name":"Department of Neurology, University Medical Center Rostock , Rostock 18147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-7791","authenticated-orcid":false,"given":"Andreas","family":"Hermann","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , Rostock 18147 ,","place":["Germany"]},{"name":"Department of Neurology, University Medical Center Rostock , Rostock 18147 ,","place":["Germany"]},{"name":"Translational Neurodegeneration Section \u2018Albrecht Kossel\u2019, Department of Neurology, University Medical Center Rostock , Rostock 18147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dyrba","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , Rostock 18147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7323-4789","authenticated-orcid":false,"given":"Julia","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , Rostock 18147 ,","place":["Germany"]},{"name":"Department of Neurology, University 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