Abstract
Background
Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer’s disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer’s disease and also prevent the progression from prodromal Alzheimer’s disease to dementia. We sought in this review to examine the evidence for this proposition.
Objectives
To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer’s disease.
Search methods
We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review.
Selection criteria
We included randomised, placebo‐controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks.
Data collection and analysis
Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive‐functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta‐analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD.
Main results
We included three randomised, placebo‐controlled trials investigating Souvenaid in 1097 community‐dwelling participants with Alzheimer’s disease. One study each included participants with prodromal AD, mild AD dementia and mild‐to‐moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid.
One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence).
In prodromal AD, and in mild and mild‐to‐moderate Alzheimer’s disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild‐to‐moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive‐functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer’s disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild‐to‐moderate Alzheimer’s disease dementia after 24 weeks (moderate quality of evidence).
Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid.
Authors’ conclusions
Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild‐to‐moderate stages of dementia. Conflicting evidence on combined cognitive‐functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long‐term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.
Plain language summary
The dietary supplement Souvenaid for preventing dementia or delaying cognitive decline in people with Alzheimer’s disease
Review question
We investigated whether people with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) can reduce their risk of developing dementia with a patented dietary supplement called Souvenaid. We also investigated the effect of Souvenaid on memory or other thinking skills, ability to carry out daily activities, and side effects in people with MCI or any stage of dementia due to AD.
Background
Alzheimer’s disease is a brain disease. It is the commonest cause of dementia among older people. A person is said to have dementia when there has been a decline in their memory and thinking skills which is severe enough to stop them being fully independent in all their daily activities. Because AD develops slowly, it is also possible to pick up symptoms before dementia is fully developed. This pre‐dementia stage, when people with AD have a detectable decline in memory and thinking skills but are still able to manage their usual activities independently, is known as mild cognitive impairment due to AD, or ‘prodromal’ AD.
Souvenaid is a patented mix of vitamins and minerals (Fortasyn Connect™) which was designed to improve brain function in AD. It is a drink which is to be taken once a day. It is intended to be consumed under medical supervision, in addition to the usual diet.
Search for evidence
We systematically searched for randomised controlled trials (RCTs) which were published up to June 2020 and which compared treatment with Souvenaid for at least 16 weeks with treatment with a dummy supplement (a placebo). For the comparison to be fair, it had to be decided randomly whether each participant was given Souvenaid or the placebo.
Key results
We found three RCTs with a total of 1097 participants to include in the review. Two of the trials investigated Souvenaid in people with dementia over a treatment period of 24 weeks. One of these included 527 participants with mild‐to‐moderate dementia due to AD and the other included 259 participants with mild dementia due to AD. The third trial investigated the use of Souvenaid for two years in 311 people with prodromal AD.
We considered all of the trials to be well‐designed, but because of differences between them in the severity of the participants’ symptoms and in the way the researchers measured their results, we were not able to combine the data numerically from the single trials. All the results we report are therefore based on single trials, which leads us to have only moderate confidence in the findings of this review. This means that results could be changed by further research.
We found that people with prodromal AD who took Souvenaid daily for two years were probably no more or less likely than those taking placebo to develop dementia.
Souvenaid probably had little or no effect on measures of memory or other thinking skills in people with prodromal AD (after two years of treatment) or with mild or mild‐to‐moderate dementia due to AD (after 24 weeks of treatment). It also probably had little or no effect on the ability of people with mild or mild‐to‐moderate dementia due to AD to manage everyday activities (again after 24 weeks).
Two studies used an outcome scale which combined memory and thinking skills with practical skills (described as a combined cognitive‐functional outcome). There was probably a small benefit of Souvenaid on this outcome among people with prodromal AD who took Souvenaid for two years. However, there was probably little or no effect of Souvenaid on this outcome among people with mild‐to‐moderate AD dementia who took it for 24 weeks.
There were only a few adverse events reported in the trials, and it was not possible to know whether any of them were side effects of Souvenaid.
Study funding sources
Two studies were funded by the manufacturer of Souvenaid. The third study (in prodromal AD) was funded by European grants.
