Effect Size Analyses of Souvenaid in Patients with Alzheimer’s Disease

Abstract

Background: Souvenaid® (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes.Objective: To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm.Methods: Data from all three reported randomized controlled trials of Souvenaid in Alzheimer’s disease (AD) dementia (Souvenir I, Souvenir II, and S-Connect) and an open-label extension study were included in analyses of effect size for cognitive, functional, and behavioral outcomes. Effect size was determined by calculating Cohen’s d statistic (or Cramér’s V method for nominal data), number needed to treat and number needed to harm. Statistical calculations were performed for the intent-to-treat populations.Results: In patients with mild AD, effect sizes were 0.21 (95% confidence intervals: –0.06, 0.49) for the primary outcome in Souvenir II (neuropsychological test battery memory z-score) and 0.20 (0.10, 0.34) for the co-primary outcome of Souvenir I (Wechsler memory scale delayed recall). No effect was shown on cognition in patients with mild-to-moderate AD (S-Connect). The number needed to treat (6 and 21 for Souvenir I and II, respectively) and high number needed to harm values indicate a favorable harm:benefit ratio for Souvenaid versus control in patients with mild AD.Conclusions: The favorable safety profile and impact on outcome measures converge to corroborate the putative mode of action and demonstrate that Souvenaid can achieve clinically detectable effects in patients with early AD.

Omega-3 fatty acids, lipids, and apoE lipidation in Alzheimer's disease: a rationale for multi-nutrient dementia prevention

“…In a post hoc analysis, B-vitamin supplementation in patients with MCI resulted in reduced brain atrophy and increased cognitive improvement, which was limited to the subgroup of patients that had the highest blood-level of n3-FAs, especially DHA (264,283,284). A set of four clinical trials that were based on the FC multi-nutrient formulation showed improved memory performance (285,286), increased neurophysiological measures of synaptic activity, and enhanced functional connectivity in the brain (286,287), but did not slow cognitive decline in mild to moderate AD (288,289). Results from the fourth clinical trial, which studies this intervention in prodromal (pre dementia) AD, have not yet been published.…”

Neuroprotective Effects of Choline and Other Methyl Donors

“…The role of the micronutrient choline and other methyl-donors in the functioning of the mature brain has been studied in animal models and in humans. For example, choline has been shown to exert neuroprotective effects by lessening or delaying symptoms of cognitive impairments and memory decline with aging [89][90][91], symptoms often seen in individuals suffering from neurodegenerative disorders such as Alzheimer's disease. Could then an individualized nutrition-based approach be adopted early on in life to boost mental health or delay the progression of these debilitating diseases with aging?…”

Screening and measurement of cognitive impairment in psychiatry

“…Here, effect size has emerged as a convenient lingua franca for comparing performance between study cohorts. 8 These are usually comparisons of "typical controls" with those who meet generally accepted criteria for diagnostic categories, such as can be found in the World Health Organization (WHO) International Statistical Classification of Diseases and Related Health Problems. 9 In psychiatry, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is also commonly applied.…”