Phosphatidylserine (PS) may have beneficial effects on cognitive functions. We evaluated the efficacy of a novel preparation of PS containing omega-3 long-chain polyunsaturated fatty acids attached to its backbone (PS-DHA) in non-demented elderly with memory complaints.

157 participants were randomized to receive either PS-DHA or placebo for 15 weeks. Efficacy measures, assessed at baseline and endpoint, included the Rey Auditory Verbal Learning Test, Rey Complex Figure Test, and a computerized cognitive battery. Clinicians' Global Impression of Change was assessed following 7 and 15 weeks of treatment.

131 participants completed the study although 9 were excluded from the efficacy analysis due to protocol violation. At endpoint, verbal immediate recall was significantly improved in the PS-DHA group compared to the placebo group. Post-hoc analysis revealed that a subset of participants with relatively good cognitive performance at baseline had significant treatment-associated improvements in immediate and delayed verbal recall, learning abilities, and time to copy complex figure. These favorable results were further supported by responder analysis.

The results indicate that PS-DHA may improve cognitive performance in non-demented elderly with memory complaints. Post-hoc analysis of subgroups suggests that participants with higher baseline cognitive status were most likely to respond to PS-DHA. The results of this exploratory study should be followed up by additional studies aimed at confirming the present tentative conclusions.