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New insights from AD and MCI nutritional marker study

Specific nutrients that are required for phospholipid synthesis are lower in blood and cerebrospinal fluid (CSF) in people with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) compared to control subjects.This is the outcome of a study recently published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. CSF levels give specific insights into the availability of nutrients in the brain.

The increasing importance of nutrients in the brain

Nick van Wijk, Senior Scientist at Danone Research & Innovation: “The brain like any other organ needs specific nutrients to function properly. This study finds that people suffering from MCI and AD have lower concentrations in blood of nutrients that are needed for building phospholipids.”

“Phospholipids are a class of lipids that are essential for brain function”, Van Wijk continues. “They are key components of plasma membranes, the “skin” of brain cells. Proper membrane formation is involved in many cellular functions, including communication between brain cells, which happens at the so called synapse. Synapses are connections between neurons. Synapses allow transmission of signals from one brain cell to another and therefore make it possible to create and recall memories. In summary, phospholipid synthesis is important for proper synapse function.”

It is generally accepted that AD is characterized by a loss of synapses in the earliest phases of the disease. Nutrition is increasingly recognized as an important factor in the progression of AD. Optimal synaptic membrane formation depends on the availability of specific nutrients. Consequently, insufficient availability of these nutrients may restrict membrane formation and contribute to synapse loss in AD.

Relevant research

So far only a limited number of studies have reported levels of a set of nutrients, in both blood and CSF levels, as well as in AD and MCI patients. In this cross-sectional study the researchers analyzed samples from patients from the Amsterdam Dementia Cohort biobank. This collaboration between VUmc, Maastricht UMC+, and Danone Research & Innovation allowed studying a set of nutrients, rather than one nutrient, in both blood and CSF, rather than one or the other, from the same patients with either MCI or AD.

Such data are important, because blood levels are valuable in assessing nutritional status, while CSF levels give specific insights into the availability of nutrients in the brain. Moreover, it is of interest to know if changes in nutritional status already occur in MCI. MCI is a pre-dementia stage in which synaptic pathological changes are observed but have not yet accumulated to an irreversible degree.

Conclusion and future research

Study results revealed lower blood and CSF concentrations of uridine, folate, and choline in people with MCI and AD compared with control subjects. These nutrients are involved in synaptic membrane formation. Such disease-specific nutritional deficits could exacerbate synaptic dysfunction and synapse loss in MCI, in which the potential for successful intervention is arguably higher.

The current observations warrant exploration of the application of nutritional strategies in the early stages of AD, such as specific dietary management. Additional research is needed to understand the extent of AD-specific changes in nutritional status, and if these changes are cause or consequence of the disease.

Funding

This work is part of the Nutrition the Unrecognized Determinant for Alzheimer’s Disease (NUDAD) project, which received a grant from the Food, Brain and Cognition program of the Dutch Organisation for Scientific Research (NWO: Nederlandse Organisatie voor Wetenschappelijk Onderzoek).

The study was executed in collaboration with VU University Medical Center and Maastricht UMC