{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:37:00Z","timestamp":1792103820329,"version":"4.4.0"},"reference-count":86,"publisher":"BMJ","funder":[{"name":"Neurosciences Foundation","award":["173503"],"award-info":[{"award-number":["173503"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dementia is a common, debilitating feature of late Parkinson\u2019s disease (PD). PD dementia (PDD) is associated with \u03b1-synuclein propagation, but coexistent Alzheimer\u2019s disease (AD) pathology may coexist. Other pathologies (cerebrovascular, transactive response DNA-binding protein 43 (TDP-43)) may also influence cognition. We aimed to describe the neuropathology underlying dementia in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Systematic review of autopsy studies published in English involving PD cases with dementia. Comparison groups included PD without dementia, AD, dementia with Lewy bodies (DLB) and healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>44 reports involving 2002 cases, 57.2% with dementia, met inclusion criteria. While limbic and neocortical \u03b1-synuclein pathology had the strongest association with dementia, between a fifth and a third of all PD cases in the largest studies had comorbid AD. In PD cases with dementia, tau pathology was moderate or severe in around a third, and amyloid-\u03b2 pathology was moderate or severe in over half. Amyloid-\u03b2 was associated with a more rapid cognitive decline and earlier mortality, and in the striatum, distinguished PDD from DLB. Positive correlations between multiple measures of \u03b1-synuclein, tau and amyloid-\u03b2 were found. Cerebrovascular and TDP-43 pathologies did not generally contribute to dementia in PD. TDP-43 and amyloid angiopathy correlated with coexistent Alzheimer pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While significant \u03b1-synuclein pathology is the main substrate of dementia in PD, coexistent pathologies are common. In particular, tau and amyloid-\u03b2 pathologies independently contribute to the development and pattern of cognitive decline in PD. Their presence should be assessed in future clinical trials where dementia is a key outcome measure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>CRD42018088691.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2019-321111","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T17:15:34Z","timestamp":1566580534000},"page":"jnnp-2019-321111","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":85,"title":["Neuropathology of dementia in patients with Parkinson\u2019s disease: a systematic review of autopsy studies"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8536-7597","authenticated-orcid":false,"given":"Callum","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Malek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Grosset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7259-9505","authenticated-orcid":false,"given":"Breda","family":"Cullen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Gentleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald G","family":"Grosset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,8,23]]},"reference":[{"key":"2020042902321788000_90.11.1234.1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000187889.17253.b1"},{"key":"2020042902321788000_90.11.1234.2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21507"},{"key":"2020042902321788000_90.11.1234.3","doi-asserted-by":"publisher","DOI":"10.2217\/imt.13.162"},{"key":"2020042902321788000_90.11.1234.4","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.neurol.2014.10.003","article-title":"Amyloid beta peptide immunotherapy in Alzheimer disease","volume":"170","year":"2014","journal-title":"Rev Neurol"},{"key":"2020042902321788000_90.11.1234.5","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2015.1075002"},{"key":"2020042902321788000_90.11.1234.6","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000641"},{"key":"2020042902321788000_90.11.1234.7","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1212\/WNL.0000000000002350","article-title":"Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis","volume":"86","year":"2016","journal-title":"Neurology"},{"key":"2020042902321788000_90.11.1234.8","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/S1474-4422(09)70238-8","article-title":"Neuropathological assessment of Parkinson's disease: Refining the diagnostic criteria","volume":"8","year":"2009","journal-title":"The Lancet Neurology"},{"key":"2020042902321788000_90.11.1234.9","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1111\/j.1742-1241.2008.01869.x","article-title":"Diagnosis and management of Parkinson\u2019s disease dementia","volume":"62","year":"2008","journal-title":"Int J Clin Pract"},{"key":"2020042902321788000_90.11.1234.10","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"2020042902321788000_90.11.1234.11","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.12.1791"},{"key":"2020042902321788000_90.11.1234.12","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.4.479"},{"key":"2020042902321788000_90.11.1234.13","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0612-2"},{"key":"2020042902321788000_90.11.1234.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0652-7"},{"key":"2020042902321788000_90.11.1234.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.006"},{"key":"2020042902321788000_90.11.1234.16","year":"2009","journal-title":"Assessing risk of bias in included studies, in Cochrane handbook for systematic reviews of interventions, version 5.0.0 [updated February 2008], J.P.T. 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