Genistein may delay dementia onset in prodromal Alzheimer’s disease

Genistein significantly improves immediate recall, verbal learning, executive function, attention, and immediate visual memory and slows down amyloid-beta deposition in the anterior cingulate gyrus of patients with prodromal Alzheimer’s disease (AD), according to the results of the randomized, double-blind, placebo-controlled phase II GENIAL study.

Genistein is a natural isoflavone that is mainly derived from legumes. It was previously shown to significantly improve cognition in an APP/PS1 mouse model of AD by lowering amyloid levels in the brain, improving antioxidant status, and lowering brain inflammation. [J Alzheimers Dis 2016;51:701-711; Free Radic Biol Med 2022;183:127-137; Mech Ageing Dev 2022;doi:10.1016/j.mad.2022.111665]

The present study included 27 patients (male, 18; age, 54–75 years) with prodromal AD, who were randomized 1:1 to receive either one capsule of genistein (60 mg) or placebo, administered orally twice per day for up to 12 months. The primary outcome was to determine differences in amyloid-beta deposition in the brain after 1 year of treatment. [Alzheimers Res Ther 2022;doi:10.1186/s13195-022-01097-2]

Beta-amyloid deposition was measured by flutemetamol PET. The standardized uptake value ratios (SUVR) were found to be statistically different between the placebo and genistein groups in only one part of the brain – the anterior cingulate gyrus. After 12 months, ¹⁸F-flutemetamol uptake in this area rose in placebo-treated patients (p=0.036) but did not increase in genistein-treated ones (p=0.878). “Recent lipidomic work has shown that the anterior cingulate gyrus, which plays a unique role in cognition and emotion, is one of the areas of the brain particularly prone to age-related changes,” noted the researchers. [Geroscience 2022;44:763-783; Free Radic Biol Med 2016;95:1-15; J Neuropsychiatry Clin Neurosci 2011;23:121-125]

The secondary outcome was to analyze the effect of genistein on progressive loss of cognition after 6 months and 1 year of treatment, for which six neurocognitive tests were used. Genistein treatment led to significant improvements in two of the tests, namely, Complutense Verbal Learning Test (p=0.031), which provides information on immediate recall and verbal learning, and Rey Complex Figure Test (p=0.002), which assesses executive functions, attention, and immediate visual memory. Although not statistically significant, there was a tendency for improvement in the remaining neurocognitive tests among genistein-treated patients at 1 year.

“We did not observe improvements at 6 months of treatment, but did see them after 1 year. This time-cause effect underpins the importance of relatively long-term treatment to prevent or delay the transition to full-blown dementia in prodromal Alzheimer’s patients,” highlighted the researchers.