Date Published: July 26, 2017
Publisher: BioMed Central
Author(s): Anne Rijpma, Marinette van der Graaf, Marieke M. Lansbergen, Olga Meulenbroek, Aysun Cetinyurek-Yavuz, John W. Sijben, Arend Heerschap, Marcel G. M. Olde Rikkert.
Synaptic dysfunction contributes to cognitive impairment in Alzheimer’s disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer’s disease.
Thirty-four drug-naive patients with mild Alzheimer’s disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio.
MRS data from 33 patients (60–86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06–0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00–0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters.
MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer’s disease, in line with findings in preclinical studies.
Netherlands Trial Register, NTR3346. Registered on 13 March 2012.
The online version of this article (doi:10.1186/s13195-017-0286-2) contains supplementary material, which is available to authorized users.
Synaptic dysfunction is a major contributing factor to cognitive impairment in Alzheimer’s disease (AD) [1, 2] and may be caused by deficits in neuronal membrane composition and function [3, 4]. Because the neuronal membrane is composed mainly of phospholipids , interventions that target brain phospholipid metabolism may affect cognitive function in AD.
In this study, we investigated whether the medical food Souvenaid, containing nutritional precursors and cofactors for phospholipid membrane formation (i.e., FC), influenced brain phospholipid metabolism in mild AD. The observed effects indicate that this specific multinutrient combination not only raises circulating levels of phospholipid precursors after 4 weeks but also affects the balance between brain metabolites of phospholipid formation and breakdown in patients with mild AD. In addition, levels of tCho were higher after the intervention in comparison with the control product, whereas metabolic measures of neural integrity, gliosis, and energy metabolism were not significantly affected.
This exploratory, double-blind, randomized controlled study shows that the medical food Souvenaid affects phospholipid metabolism across multiple brain regions in mild AD after only 4 weeks. This could lead to increased neuronal membrane formation, which would support the hypothesized mode of action of this multinutrient intervention. Larger and longer randomized controlled trials are needed to determine long-term effects on phospholipid formation, synaptic function, and cognition in persons with and at risk for AD.