{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:01:30Z","timestamp":1777395690548,"version":"3.51.4"},"reference-count":89,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2019,9,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Agitation is a prevalent and difficult-to-treat symptom of Alzheimer\u2019s disease (AD). The endocannabinoid system (ECS) has been a target of interest for the treatment of agitation. However, ECS signaling may interact with AD-related changes in brain cholesterol metabolism. Elevated brain cholesterol, reflected by reduced serum 24-S-hydroxycholesterol (24S-OHC), is associated with reduced membrane fluidity, preventing ligand binding to cannabinoid receptor 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To assess whether 24S-OHC was associated with agitation severity and response to nabilone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>24S-OHC was collected from AD patients enrolled in a clinical trial on nabilone at the start and end of each phase. This allowed for the cross-sectional and longitudinal investigation between 24S-OHC and agitation (Cohen Mansfield Agitation Inventory, CMAI). Post-hoc analyses included adjustments for baseline standardized Mini-Mental Status Exam (sMMSE), and analyses with CMAI subtotals consistent with the International Psychogeriatric Association (IPA) definition for agitation (physical aggression and nonaggression, and verbal aggression).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>24S-OHC was not associated with CMAI scores cross-sectionally or longitudinally, before and after adjusting for baseline sMMSE. However, 24S-OHC was associated with greater CMAI IPA scores at baseline (F(1,36)\u200a=\u200a4.95, p\u200a=\u200a0.03). In the placebo phase only, lower 24S-OHC at baseline was associated with increases in CMAI IPA scores (b\u200a=\u200a\u201335.2, 95% CI \u201365.6 to \u20135.0, p\u200a=\u200a0.02), and decreases in 24S-OHC were associated with increases in CMAI IPA scores (b\u200a=\u200a\u201320.94, 95% CI \u201357.9 to \u20134.01, p\u200a=\u200a0.03).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>24S-OHC was associated with agitation severity cross-sectionally, and longitudinally in patients with AD. However, 24S-OHC did not predict treatment response, and does not change over time with nabilone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-190202","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T10:41:17Z","timestamp":1563532877000},"page":"21-31","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["24S-Hydroxycholesterol Is Associated with Agitation Severity in Patients with Moderate-to-Severe Alzheimer\u2019s Disease: Analyses from a Clinical Trial with Nabilone"],"prefix":"10.1177","volume":"71","author":[{"given":"Myuri","family":"Ruthirakuhan","sequence":"first","affiliation":[{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, 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