Boswellic Acids Improve Clinical Cognitive Scores and Reduce Systemic Inflammation in Patients with Mild to Moderate Alzheimer’s Disease

Article type: Research Article

Authors: Karima, Saeed^{a; *} | Aghamollaii, Vajiheh^b | Mahmoodi Baram, Somayeh^c | Balenci, Laurent^d | Lanctôt, Krista L.^e | Kiss, Alex^f | Tafakhori, Abbas^g | Mahdavi, Meisam^a | Rajaei, Shima^c | Shateri, Somayeh^a | Yarhoseini, Amir^b | Mokhtari, Farzad^c | Fotouhi, Akbar^h | Riazi, Ali^{d; *}

Affiliations: [a] Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [b] Neurology Department, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran | [c] Clinical Trial Department, Behbalin Inc., Tehran, Iran | [d] Kondor Pharma Inc. Mississauga, Ontario, Canada | [e] Departments of Psychiatry and Pharmacology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Canada | [f] Department of Research Design and Biostatistics, Sunnybrook Research Institute, Toronto, Canada | [g] Department of Neurology, School of Medicine, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran | [h] Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Correspondence: [*] Correspondence to: Saeed Karima, PhD, Assistant Professor of Biochemistry, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran. Tel.: +9821 9666 1028; Fax: +9821 9666 1029; E-mail: [email protected] and Ali Riazi, PhD, Kondor Pharma Inc., Mississauga, ON, Canada. E-mail: [email protected].

Abstract: Background: Recent therapeutic approaches for Alzheimer’s disease (AD) have had limited success. Considering the association of neuroinflammation with AD symptoms as demonstrated in multiple studies, assessment of the clinical efficacy of molecules that reduce systemic or brain inflammation is warranted. Objective: This clinical trial assessed whether boswellic acids can improve cognitive and neuropsychiatric symptoms while reducing inflammation in AD patients. Methods: A double-blind, placebo-controlled, study was conducted on 85 AD patients randomized to boswellic acids (K-Vie™ as the main ingredient in Memowell™) or placebo for 6 months. Clinical Dementia Rating–Sum of Boxes (CDR-SOB) and Mini-Mental State Examination (MMSE) scores were compared to baseline and between groups and constituted the co-primary clinical efficacy endpoints. Secondary outcomes included neuropsychiatric assessment (Neuropsychiatric Inventory-Questionnaire, NPI-Q) and assessment of AD and inflammation biomarkers. Results: Patients on K-Vie™ showed a 3.1- and 1.6-unit improvement in MMSE and CDR-SOB scores, respectively, when compared to patients on placebo. NPI-Q analysis revealed significant improvement in the K-Vie™ but not in the placebo group. Only mild gastrointestinal side effects were reported in a few patients. Patients on K-Vie™ showed improvement in plasma AD biomarkers and reduction of key inflammatory cytokines including IL-6 and TNF. Conclusion: Our results support the positive cognitive effects of boswellic acids by reducing the systemic inflammation.

Keywords: Alzheimer’s disease, boswellic acids, central nervous system, cognition, inflammation

DOI: 10.3233/JAD-221026

Journal: Journal of Alzheimer's Disease, vol. 94, no. 1, pp. 359-370, 2023