Identifying a combination of biomarkers to predict treatment response to nabilone for the treatment of agitation in Alzheimer's disease – a secondary analysis

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Publicado en:Alzheimer's & Dementia vol. 21 (Dec 1, 2025)
Autor Principal: Wang, Hui Jue (Janet)
Outros autores: Ruthirakuhan, Myuri, Herrmann, Nathan, Andreazza, Ana C., Gallagher, Damien, Verhoeff, Nicolaas Paul L.G., Kiss, Alex, Black, Sandra E., Feldman, Oriel J, Lanctôt, Krista L
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John Wiley & Sons, Inc.
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022 |a 1552-5260 
022 |a 1552-5279 
024 7 |a 10.1002/alz70857_103580  |2 doi 
035 |a 3286852212 
045 0 |b d20251201 
100 1 |a Wang, Hui Jue (Janet)  |u Sunnybrook Research Institute, Toronto, ON, Canada, 
245 1 |a Identifying a combination of biomarkers to predict treatment response to nabilone for the treatment of agitation in Alzheimer's disease – a secondary analysis 
260 |b John Wiley & Sons, Inc.  |c Dec 1, 2025 
513 |a Journal Article 
520 3 |a Background Agitation is a challenging neuropsychiatric symptom (NPS) of Alzheimer's disease (AD). A crossover trial found that nabilone significantly improved agitation in AD patients over 6 weeks compared to placebo. Here, we aim to identify a combination of biomarkers that could be used to predict treatment response to nabilone for AD‐associated agitation. Methods Agitation was assessed using the Cohen‐Mansfield Agitation Inventory (CMAI). Serum concentrations of 13 markers were measured. Linear regression was used to estimate change in CMAI due to nabilone for the high and low groups of each biomarker. Biomarkers with a difference ≥8.5 points between groups were included in subsequent multivariate models. Index scores representing the difference between expected CMAI change given nabilone and placebo were calculated and divided into quartiles. Mean difference in CMAI change and 95% confidence intervals were estimated via bootstrapping. Results Four of the 13 biomarkers which met criteria specified above were included in multivariate modeling (n = 67). Nabilone was more efficacious in participants with higher IL‐6 (estimated change in CMAI ‐15.4, standard error (SE) 5.6), higher ISO‐8 (‐14.4, SE=5.0), higher 24S‐OHC (‐14.2, SE=4.1), and lower clusterin (‐14.6, SE=4.4). Participants in Q1 of index scores demonstrated better response to nabilone with a mean difference in CMAI change of ‐20.9 (95% CI: ‐31.8, ‐9.2), while those in Q2‐4 showed no difference between treatments. Conclusions Participants with higher levels of inflammation, oxidative stress, and cholesterol metabolite were more likely to benefit from nabilone for agitation in AD. A combination of biomarkers could help in distinguishing responders and non‐responders to nabilone. 
653 |a Indexes 
653 |a Serum 
653 |a Alzheimer's disease 
653 |a Bootstrapping 
653 |a Psychiatry 
653 |a Cholesterol 
653 |a Treatment methods 
653 |a Agitation 
653 |a Changes 
653 |a Biological markers 
653 |a Bootstrap method 
653 |a Disease 
653 |a Biomarkers 
653 |a Medical treatment 
653 |a Inflammation 
653 |a Oxidative stress 
653 |a Patients 
700 1 |a Ruthirakuhan, Myuri  |u Sunnybrook Research Institute, Toronto, ON, Canada, 
700 1 |a Herrmann, Nathan  |u Sunnybrook Research Institute, Toronto, ON, Canada, 
700 1 |a Andreazza, Ana C.  |u University of Toronto, Toronto, ON, Canada, 
700 1 |a Gallagher, Damien  |u Sunnybrook Research Institute, Toronto, ON, Canada, 
700 1 |a Verhoeff, Nicolaas Paul L.G.  |u Baycrest Hospital, Toronto, ON, Canada, 
700 1 |a Kiss, Alex  |u Sunnybrook Research Institute, Toronto, ON, Canada, 
700 1 |a Black, Sandra E.  |u Sunnybrook Research Institute, Toronto, ON, Canada, 
700 1 |a Feldman, Oriel J  |u Sunnybrook Research Institute, Toronto, ON, Canada, 
700 1 |a Lanctôt, Krista L  |u Sunnybrook Research Institute, Toronto, ON, Canada, 
773 0 |t Alzheimer's & Dementia  |g vol. 21 (Dec 1, 2025) 
786 0 |d ProQuest  |t Consumer Health Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3286852212/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3286852212/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch