Cognitive Effects of Soy Isoflavones in Patients with Alzheimer’s Disease

Article type: Research Article

Authors: Gleason, Carey E.^{a; b; c; *} | Fischer, Barbara L.^{a; b} | Dowling, N. Maritza^{c; d} | Setchell, Kenneth D.R.^e | Atwood, Craig S.^{a; b} | Carlsson, Cynthia M.^{a; b; c} | Asthana, Sanjay^{a; b; c}

Affiliations: [a] Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA | [b] Geriatric Research, Education, and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA | [c] Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA | [d] Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, WI, USA | [e] Division of Pathology and Laboratory Medicine, Department of Pediatrics University of Cincinnati, Cincinnati, OH, USA

Correspondence: [*] Correspondence to: Carey E. Gleason, PhD, MS, Madison VA GRECC (11G), 2500 Overlook Terrace, Madison, WI 53705, USA. Tel.: +1 608 280 7000; Fax: +1 608 280 7291; [email protected]

Abstract: Background: In a previous trial, treatment with soy isoflavones was associated with improved nonverbal memory, construction abilities, verbal fluency, and speeded dexterity compared to treatment with placebo in cognitively healthy older adults. Objective: The current trial aimed to examine the potential cognitive benefits of soy isoflavones in patients with Alzheimer’s disease. Methods: Sixty-five men and women over the age of 60 were treated with 100 mg/day soy isoflavones, or matching placebo capsules for six months. APOE genotype was determined for all participants. Cognitive outcomes and plasma isoflavone levels were measured at baseline, and at two additional time points: three and six months after baseline. Results: Of the sixty-five participants enrolled, thirty-four (52.3% ) were women, and 31 (47.7% ) were APOE ɛ4 positive. Average age was 76.3 (SD = 7.2) years. Fifty-nine (90.8% ) subjects completed all study visits. Plasma isoflavone levels increased in subjects treated with soy isoflavones compared to baseline and to placebo, although intersubject variability in plasma levels was large. No significant differences in treatment effects for cognition emerged between treatment groups or genders. Exploratory analyses of associations between changes in cognition and plasma isoflavone levels revealed an association between equol levels, and speeded dexterity and verbal fluency. Conclusions: Six months of 100 mg/day treatment with soy isoflavones did not benefit cognition in older men and women with Alzheimer’s disease. However, our results suggest the need to examine the role of isoflavone metabolism, i.e., the ability to effectively metabolize soy isoflavones by converting daidzen to equol when attempting to fully clarify the cognitive effects of isoflavones.

Keywords: Alzheimer’s disease, clinical trial, cognition, daidzein, equol, genistein, phytoestrogens, soy isoflavones

DOI: 10.3233/JAD-142958

Journal: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 1009-1019, 2015