Nutrition and aging: is there a link to cognitive health?

There is a growing body of literature suggesting that what we eat may affect our mental health. Empirical observations of gastrointestinal symptoms following emotive stress find their physiological basis on the sympathetic and parasympathetic nervous systems connections: in fact, brain is responsible for gut motility, secretion, nutrient delivery and microbial balance. Lately, it has been demonstrated a neural circuit between the so-called enteroendocrine cells (sited within the layer of epithelial cells in the gut) and the brain, which can mediate, similarly to taste or olfactory receptor cells, gut-brain sensory transduction (through vagal neurons; Kaelberer et al. 2018). This communication between gut and brain may be even more complex while involving other organs: for instance, after exposure to gut-derived bacteria via the portal circulation, the liver may respond with activation of the innate and adaptive immune system, leading to hepatic damage (gut–liver–brain axis; Konturek et al. 2018). Besides these direct connections, the gut affects the brain through alteration of its microbiota composition (Salvucci 2019): the microbiota–gut–brain axis refers to those biochemical signalling events that take place in the guts following a dysbiotic gut microbiota and to harmful microbial by-products (such as ammonia, indoles, oxindoles and endotoxins) which may affect brain health (Mancini et al. 2018). In this context, food may represent a key factor to modulate such messaging or even improving or affecting one’s mental health. Characteristics related to diet quality, such as richness in fibre or, on the contrary, animal protein and refined sugars, may impact the production and subsequent absorption of short-chain fatty acids (SCFAs), acetate, butyrate and propionate, which are known to play a role in local and general inflammation. This low-grade inflammation occurs physiologically during aging (so-called inflammaging), but lifestyle habits, including dietary factors, may play an important role for its regulation (so-called metaflammation; Franceschi et al. 2018). Inflammation has been suggested to be a key step for the majority of chronic non-communicable diseases, including cognitive decline.

In this issue, Zhou et al. showed that elevated levels of homocysteine, an amino acid biosynthesised from methionine that can be converted into cysteine in presence of B vitamins, is associated with a higher likelihood of mild cognitive impairment (MCI), a transitional state between normal aging and dementia (Zhou et al. 2020). While vitamin B12 levels were not significantly associated with this clinical condition when adjusting for liver transaminase levels, the authors also showed that folate intake was inversely associated with MCI. These findings suggest a potential role for liver health and homocysteine metabolism in affecting cognitive health: high levels of homocysteine have been associated with a number of neurodegenerative diseases, including cognitive function in Parkinson’s disease (Xie et al. 2017), multiple sclerosis (Fahmy et al. 2018) and Alzheimer’s or vascular dementia patients (Zhou and Chen 2019). Folate, one of the B vitamins necessary for DNA and RNA may improve cognitive function by decreasing homocysteine levels, improve vascular health, attenuating inflammatory status, modification of cerebral folic acid deficiency and antioxidant responses (Enderami et al. 2018). Folic acid (precursor of folate) also plays an important role in neuroplasticity and in the maintenance of neuronal integrity (Kronenberg et al. 2009). An intriguing hypothesis also involves the impact of folate in DNA methylation as means for propagating the effects of environmental inputs on neurological and behavioural development (Irwin et al. 2016). Testing for homocysteine levels may help to identify people at higher risk of developing cognitive decline; in these individuals, future studies promoting a diet characterised by decent content of folate might help underling whether there is the possibility to slow down cognitive impairment. Bearing in mind that the study design cannot provide causal relation between exposure and outcome, it is desirable that future studies would also take into account liver functionality and the potential role of gut microbiota in mediating the hypothesised effects.

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