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The\n                    <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>\n                    and cholesterol metabolic pathways in the brain are autonomous from their systemic counterparts and are interrelated through the cholesterol metabolite 27\u2010hydroxycholesterol (27\u2010\n                    <jats:styled-content style=\"fixed-case\">OHC<\/jats:styled-content>\n                    ). These systems contribute to memory and dementia pathogenesis through interference in the amyloid\u2010beta cascade, vascular mechanisms, glucose metabolism, apoptosis, neuroinflammation and oxidative stress. Previous studies examining the relationship between these treatments and cognition and dementia risk have produced inconsistent results. Defining the blood\u2013brain barrier penetration of these medications has been challenging, and the mechanisms of action on cognition are not clearly established. Potential biases are apparent in epidemiological and clinical studies, such as reverse epidemiology, indication bias, problems defining medication exposure, uncertain and changing doses, and inappropriate grouping of outcomes and medications. This review summarizes current knowledge of the brain cholesterol and\n                    <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>\n                    metabolism and the mechanisms by which these pathways affect neurodegeneration. The putative mechanisms of action of statins and medications inhibiting the\n                    <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>\n                    will be examined, together with prior clinical and animal studies on their effects on cognition. We review prior epidemiological studies, analysing their strengths and biases, and identify areas for future research. Understanding the pathophysiology of the brain cholesterol system and\n                    <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>\n                    and their links to neurodegeneration has enormous potential. In future, well\u2010designed epidemiological studies could identify potential treatments for Alzheimer's disease (\n                    <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\n                    ) amongst medications that are already in use for other indications.\n                  <\/jats:p>","DOI":"10.1111\/joim.12838","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T10:15:54Z","timestamp":1538129754000},"page":"620-642","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Connecting the brain cholesterol and renin\u2013angiotensin systems: potential role of statins and\n                    <scp>RAS<\/scp>\n                    \u2010modifying medications in dementia"],"prefix":"10.1111","volume":"284","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5498-8320","authenticated-orcid":false,"given":"B.","family":"Petek","sequence":"first","affiliation":[{"name":"Division of Neurogeriatrics Department of Neurobiology, Care Sciences and Society Karolinska Institutet Stockholm Sweden"},{"name":"Department of Neurology University Medical Centre Ljubljana Slovenia"},{"name":"University of Ljubljana Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Villa\u2010Lopez","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics Department of Neurobiology, Care Sciences and Society Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Loera\u2010Valencia","sequence":"additional","affiliation":[{"name":"Center for Alzheimer Research Division of Neurogeriatrics Department of Neurobiology, Care Sciences and Society Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Gerenu","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics Department of Neurobiology, Care Sciences and Society Karolinska Institutet Stockholm Sweden"},{"name":"Department of Neurosciences Biodonostia Health Research Institute San Sebastian Spain"},{"name":"Center for Networked Biomedical Research in Neurodegenerative Diseases, CIBERNED Health Institute Carlos III Ministry of Economy and Competitiveness Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Winblad","sequence":"additional","affiliation":[{"name":"Division of Neurogeriatrics Department of Neurobiology, Care Sciences and Society Karolinska Institutet Stockholm Sweden"},{"name":"Department of Geriatric Medicine Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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