Abstract | BACKGROUND: Agitation is a prevalent and difficult-to-treat symptom of Alzheimer's 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. OBJECTIVE: To assess whether 24S-OHC was associated with agitation severity and response to nabilone. METHODS: 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). RESULTS: 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) = 4.95, p = 0.03). In the placebo phase only, lower 24S-OHC at baseline was associated with increases in CMAI IPA scores (b = -35.2, 95% CI -65.6 to -5.0, p = 0.02), and decreases in 24S-OHC were associated with increases in CMAI IPA scores (b = -20.94, 95% CI -57.9 to -4.01, p = 0.03). CONCLUSION: 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.
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Authors | Myuri Ruthirakuhan, Nathan Herrmann, Ana C Andreazza, Nicolaas Paul L G Verhoeff, Damien Gallagher, Sandra E Black, Alex Kiss, Krista L Lanctôt |
Journal | Journal of Alzheimer's disease : JAD
(J Alzheimers Dis)
Vol. 71
Issue 1
Pg. 21-31
( 2019)
ISSN: 1875-8908 [Electronic] Netherlands |
PMID | 31322567
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Anxiety Agents
- Hydroxycholesterols
- nabilone
- 24-hydroxycholesterol
- Dronabinol
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Topics |
- Aged, 80 and over
- Alzheimer Disease
(complications, psychology)
- Anti-Anxiety Agents
(therapeutic use)
- Cross-Sectional Studies
- Dronabinol
(analogs & derivatives, therapeutic use)
- Female
- Humans
- Hydroxycholesterols
(blood, metabolism)
- Longitudinal Studies
- Male
- Psychomotor Agitation
(blood, drug therapy, metabolism)
- Treatment Outcome
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