A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer's Disease

Article type: Research Article

Authors: Remington, Ruth^{a; 2} | Bechtel, Cynthia^{b; 1} | Larsen, David^{c; 1} | Samar, Annemarie^{d; 1; 2} | Doshanjh, Laura^f | Fishman, Paul^e | Luo, Yuan^{e; 3} | Smyers, Kathleen^a | Page, Robert^b | Morrell, Christopher^f | Shea, Thomas B.^{a; *}

Affiliations: [a] University of Massachusetts Lowell, Lowell, MA, USA | [b] Framingham State University, Framingham, MA, USA | [c] Advanced Memory Dynamics, Layton, UT, USA | [d] Worcester State University, Worcester, MA, USA | [e] University of Maryland, College Park, MD, USA | [f] Loyola University Maryland, Baltimore, MD, USA

Correspondence: [*] Correspondence to: Thomas B. Shea, PhD, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA. Tel.: +1 978 934 2881; Fax: +1 978 934 3044; E-mail: [email protected].

Note: [1] These authors, listed in alphabetical order, contributed equally to this study.

Note: [2] Present address: Framingham State University, Framingham, MA, USA.

Note: [3] Present address: NIH, Bethesda, MD, USA.

Abstract: Background:Increasing evidence points toward the efficacy of nutritional modifications in delaying cognitive decline and mood/behavioral difficulties in Alzheimer’s disease (AD). Nutritional supplementation with individual agents has shown varied results suggesting the need for combinatorial intervention. Objective:We set out to determine whether nutritional intervention could positively impact cognitive performance and behavioral difficulties for individuals diagnosed with AD. Methods:A double-blind, multi-site, phase II study (ClinicalTrials.gov NCT01320527; Alzheimer’s Association Trialmatch) was conducted in which 106 individuals with AD were randomized to a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or placebo for 3 or 6 months, followed by an open-label extension where participants received NF for 6 additional months. Results:The NF cohort improved versus the placebo cohort within 3 months (Clox-1 p = 0.0083, 95%CI [0.4481, 2.9343]; Dementia Rating Scale p = 0.0266, 95%CI [0.1722, 2.7171]). Caregivers reported non-significant improvements in Neuropsychiatric Inventory. Both cohorts improved or maintained baseline performance during open-label extensions. Activities of Daily Living did not change for either cohort. Conclusions:These findings extend phase I studies where NF maintained or improved cognitive performance and mood/behavior.

Keywords: Acetyl-L-carnitine, Alzheimer's disease, B vitamins, behavioral difficulties, cognitive decline, N-acetyl cysteine, nutrition, supplement, S-adenosyl methionine, vitamin E

DOI: 10.3233/JAD-142499

Journal: Journal of Alzheimer's Disease, vol. 45, no. 2, pp. 395-405, 2015