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Previous research has reported a lower incidence of Alzheimer\u2019s disease-type (amnestic) dementia among individuals with a diagnosis of cancer. Both cancer and amnestic dementia are prevalent and potentially lethal clinical syndromes. The current study was conducted to investigate the association of cancer diagnosis with neuropathological and cognitive features of dementia.<\/jats:p>\n               <jats:p>Data were analysed from longitudinally evaluated participants in a community-based cohort study of brain ageing who came to autopsy at the University of Kentucky Alzheimer\u2019s Disease Research Center. These data were linked to the Kentucky Cancer Registry, a population-based state cancer surveillance system, to obtain cancer-related data. We examined the relationship between cancer diagnosis, clinical dementia diagnosis, Mini-Mental State Examination scores and neuropathological features using inverse probability weighting to address bias due to confounding and missing data. To address bias due to inclusion of participants with dementia at cohort baseline, we repeated all analyses restricted to the participants who were cognitively normal at baseline.<\/jats:p>\n               <jats:p>Included participants (n\u2009=\u2009785) had a mean\u2009\u00b1\u2009standard deviation age of death of 83.8\u2009\u00b1\u20098.6 years; 60.1% were female. Cancer diagnosis was determined in 190 (24.2%) participants, and a diagnosis of mild cognitive impairment or dementia was determined in 539 (68.7%). APOE \u025b4 allele dosage was lower among participants with cancer diagnosis compared to cancer-free participants overall (P\u2009=\u20090.0072); however, this association was not observed among those who were cognitively normal at baseline. Participants with cancer diagnosis had lower odds of mild cognitive impairment or dementia, and higher cognitive test scores (e.g. Mini-Mental State Examination scores evaluated 6 and \u22642 years ante-mortem, P\u2009&amp;lt;\u20090.001 for both comparisons). Cancer diagnosis also associated with lower odds of higher Braak neurofibrillary tangle stages (III\/IV) or (V\/VI), moderate\/frequent neuritic plaques, moderate\/frequent diffuse plaques and moderate\/severe cerebral amyloid angiopathy (all P\u2009&amp;lt;\u20090.05). By contrast, TDP-43, \u03b1-synuclein and cerebrovascular pathologies were not associated with cancer diagnosis.<\/jats:p>\n               <jats:p>Cancer diagnosis was associated with a lower burden of Alzheimer\u2019s disease pathology and less cognitive impairment. These findings from a community-based cohort with neuropathological confirmation of substrates support the hypothesis that there is an inverse relationship between cancer and Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awac035","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T20:14:15Z","timestamp":1643314455000},"page":"2518-2527","source":"Crossref","is-referenced-by-count":40,"title":["Cancer diagnosis is associated with a lower burden of dementia and less Alzheimer\u2019s-type neuropathology"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-6908","authenticated-orcid":false,"given":"Shama D","family":"Karanth","sequence":"first","affiliation":[{"name":"Aging and Geriatric Research, University of Florida , Gainesville, FL 32610 , USA"},{"name":"Cancer Control and Population Sciences Program, University of Florida , Gainesville, FL 32610 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-8094","authenticated-orcid":false,"given":"Yuriko","family":"Katsumata","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536 , USA"},{"name":"Department of Biostatistics, University of Kentucky , Lexington, KY 40536 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T","family":"Nelson","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536 , USA"},{"name":"Department of Pathology, University of Kentucky , Lexington, KY 40536 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Fardo","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536 , USA"},{"name":"Department of Biostatistics, University of Kentucky , Lexington, KY 40536 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn K","family":"McDowell","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Kentucky , Lexington, KY 40536 , USA"},{"name":"Markey Cancer Control Program, Kentucky Cancer Registry , Lexington, KY 40504 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick A","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536 , USA"},{"name":"Department of Neurology, University of Kentucky , Lexington, KY 40536 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Kryscio","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536 , USA"},{"name":"Department of Biostatistics, University of Kentucky , Lexington, KY 40536 , USA"},{"name":"Department of Statistics, University of Kentucky , Lexington, KY 40536 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R","family":"Browning","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Kentucky , Lexington, KY 40536 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejana","family":"Braithwaite","sequence":"additional","affiliation":[{"name":"Aging and Geriatric Research, University of Florida , Gainesville, FL 32610 , USA"},{"name":"Cancer Control and Population Sciences Program, University of Florida , Gainesville, FL 32610 , USA"},{"name":"Department of Population Sciences, University of Florida , Gainesville, FL 32610 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne M","family":"Arnold","sequence":"additional","affiliation":[{"name":"Markey Cancer Control Program, Kentucky Cancer Registry , Lexington, KY 40504 , USA"},{"name":"Department of Internal Medicine, University 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