Nabilone ist mit TNF-α-Reduktion und konsekutiver Agitationsabnahme assoziiert, jedoch zeigen sich keine signifikanten Effekte für den oxidativen Stressmarker 4-HNE.
Zusammenfassung
RCT-Substudie (n=38 Alzheimer-Patienten mit Agitation, 14 Wochen cross-over, Nabilon vs. Placebo); OS-Marker 4-HNE mit Agitationsschwere assoziiert (F=6,41, p=0,016); in der Nabilon-Phase: niedrigerer Baseline-TNF-α prädiktiv für Agitationsabnahme (b=1,14, p=0,045), TNF-α-Abfall korreliert mit Agitationsabfall (b=1,12, p=0,006); Hinweis auf antiinflammatorischen Wirkmechanismus.
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PopulationErwachsene mit Alzheimer-Demenz und Agitation, n=38, Substudie eines Cross-over-RCT
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InterventionNabilone (oral, 6 Wochen) mit Biomarker-Analyse (4-HNE, TNF-α)
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KontrollePlacebo (6 Wochen, Cross-over mit 1 Woche Auswaschphase)
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OutcomeNiedrigeres Baseline-TNF-α assoziiert mit Agitationsreduktion unter Nabilone (b=1,14; p=0,045); TNF-α-Abfall korreliert mit Agitationsabnahme unter Nabilone (b=1,12; p=0,006); 4-HNE-Veränderungen nicht mit Agitationsänderung assoziiert
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Moderat
Dritte von vier GRADE-Stufen, die Effektschätzung ist wahrscheinlich verlässlich.
The endocannabinoid system has been a target of interest for agitation in Alzheimer disease (AD) because of potential behavioral effects and its potential impact on mechanisms implicated in AD such as oxidative stress (OS) and neuroinflammation. We explored whether serum markers of OS and neuroinflammation were associated with response to the cannabinoid nabilone in agitated patients with AD (N = 38). All participants were enrolled in a 14-week, double-blind, cross-over trial comparing nabilone to placebo (6 weeks each) with a 1-week washout between phases. Samples were collected at the start and end of each phase. The cross-sectional relationship agitation (Cohen Mansfield Agitation Inventory) and OS and inflammatory markers were investigated to select markers of interest. Significant markers were then explored for their relationship with response. The OS marker, 4-hydroxynonenal (4-HNE; <i>F</i><sub>1, 35</sub> = 6.41, <i>P</i> = .016), and the proinflammatory cytokine, tumor necrosis factor-α (TNF-α; <i>F</i><sub>1, 29</sub> = 3.97, <i>P</i> = .06), were associated with agitation severity, and TNF-α remained significantly associated (<i>F</i><sub>2, 25</sub> = 3.69, <i>P</i> = .04) after adjustment for cognition. In the placebo phase, lower baseline 4-HNE was associated with decreases in agitation severity only (b = 0.01, <i>P</i> = .01), while lower baseline TNF-α was associated with decreases in agitation severity in the nabilone phase only (b = 1.14, <i>P</i> = .045). Changes in 4-HNE were not associated with changes in agitation severity in either phase. In the nabilone phase, lower baseline TNF-α was associated with decreases in agitation severity (b = 1.14, <i>P</i> = .045), and decreases in TNF-α were associated with decreases in agitation severity (b = 1.12, <i>P</i> = .006). These findings suggest that OS and neuroinflammation may be associated with agitation severity, while nabilone may have anti-inflammatory effects.