The role of diet in preventing and reducing cognitive decline
Cristina Angeloni
1
, Rita Businaro
2
and David Vauzour
3
*
1
School of Pharmacy, University of Camerino, 62032 Camerino, Italy;
cristina.angeloni@unicam.it
2
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of
Rome, Italy; rita.businaro@uniroma1.it
3
Norwich Medical School, Faculty of Medicine and Health Sciences, University of East
Anglia, Norwich NR4 7UQ, United Kingdom. D.Vauzour@uea.ac.uk
Correspondence should be addressed to:
Dr David Vauzour, Norwich Medical School, Faculty of Medicine and Health Sciences,
University of East Anglia, Norwich NR4 7UQ, United Kingdom. Email:
D.Vauzour@uea.ac.uk; Tel. +44(0)1603 591732; Fax: +44 (0)1603 593752
ABSTRACT
Purpose of Review
This review summarizes the most recent evidence regarding the effects of diet in preventing
and reducing age-related cognitive decline and neurodegenerative diseases.
Recent Findings
Recent evidence indicates that nutraceuticals and whole diet approaches may protect
against the development of age-related cognitive decline and pathological
neurodegeneration. The neuroprotective effects are diverse depending on the nutrient
employed and may involve a reduction of neuroinflammation, an activation of the
endogenous antioxidant defence system and a modulation of the gut microbiota structure
and function.
Summary
This review summarizes the existing evidence in favour of diet as a viable alternative
approach to directly impact cognitive decline and neurodegenerative disease. The single
nutrient (polyphenols, B vitamins, long-chain polyunsaturated fatty acids) versus whole diet
approach (Mediterranean diet, DASH, MIND, Nordic, ketogenic) is presented and
discussed. Potential mechanisms of action underlying the beneficial effects of these diets
are also described. Implementation of large-scale preventive interventions based on dietary
patterns identified as being beneficial to brain health should be a research and public health
priority, ideally in conjunction with other health-promoting lifestyle factors.
Keywords: Brain, Alzheimer’s disease, nutrition, ageing, dementia
INTRODUCTION
It has been estimated that 50 million people worldwide suffer from Alzheimer’s disease (AD),
the most common type of dementia. If no breakthrough can be made to prevent the disease
or delay its onset, the number of patients is anticipated to reach 152 million by 2050 (1).
Assuming a curvilinear association between age and dementia risk, a 2 year delay in onset
would reduce population incidence by 22% by 2047 (2), resulting in 25 million fewer cases
worldwide (3). Existing drug treatments for neurodegenerative conditions rarely curtail the
underlying disease processes, and consequently there is an urgent need to develop
alternative strategies to directly prevent, slow, and even stop neurodegeneration. Lifestyle
strategies such as nutritional interventions have potential to be a safe, cheap, and effective
alternative to protect against age-related cognitive decline and neurodegeneration, resulting
in significant personal and societal benefits (4). This review aims to summarise the existing
evidence in favour of diet either in form of nutraceuticals or whole diet as a viable alternative
approach to directly impact cognitive decline and neurodegenerative disease. Some
mechanistic considerations will also be described.
NUTRACEUTICALS
Accumulating evidence indicates that nutraceuticals such as polyphenols, B vitamins,
polyunsaturated fatty acids (PUFAs) and other nutritional components can have beneficial
effects on cognitive impairment associated to normal aging and/or neurodegenerative
diseases like AD. We will describe below the impact of such nutritional components on brain
functions.
Polyphenols
Polyphenols are a large family of phytochemicals widely distributed in the plant kingdom and
present in fruits, vegetables, nuts, seeds, flowers and other plants used for human
consumption. They can be classified according to the number of phenol rings presented and
the structural components that bind these rings in phenolic acids (hydroxycinnamic and
hydroxybenzoic acids), flavonoids (benzene rings) and less common stilbene and lignans,
although other categorizations exist (5). Previous research has demonstrated that different
purified polyphenols such as resveratrol, curcumin, anthocyanin, ferulic acid, catechin and
epicatechin were able to prevent cognitive decline in experimental animal models of aging
and degenerative diseases (6-10). A plethora of observational and intervention studies
observed a positive correlation between cognitive decline and the supplementation of
different products rich in polyphenols like cocoa, berries, green tea and grape (11-15).
However, not all studies investigating the effects of polyphenols on cognitive decline
reported positive results. A recent meta-analysis of 34 clinical trials concluded that although
some polyphenols might improve specific markers of cognitive status, definitive
recommendations for the use of these compounds in the prevention of cognitive decline are
currently not applicable (16). This is partly due to differences between individuals in the
absorption, distribution, metabolism and excretion of bioactive compounds (17) as well as
to heterogeneity in their biological response (18). The major determinants responsible for
the between‐subject variability may include genetic (Single Nucleotide Polymorphisms) and
non‐genetic factors (gut microbiota composition, sex, age, dietary habits, etc) which are only
beginning to be explored and may differ depending on the compounds (19).
B-Vitamins
B vitamins have been suggested to have a positive effect on cognitive functions thanks to
their ability to counteract the increase of homocysteine during aging that is related to
cognitive impairment (20, 21). A randomized, double blind, placebo controlled study that
involved 818 participants aged 50–70 years, evidenced that a supplementation of 800
g/day of folic acid significantly improved domains of cognitive function that tend to decline
with age (22). The clinical trial (VITACOG) demonstrated that B‐vitamin supplementation
(folic acid 0.8 mg, vitamin B
6
20 mg, vitamin B
12
0.5 mg) for 2 years in participants aged 70
years and over with MCI reduced average brain atrophy rate (23, 24), ameliorated global
cognition, episodic memory and semantic memory (25). Furthermore, the Singapore
Chinese Health Study including 16,948 participants showed that higher dietary intakes of
riboflavin and folate in midlife were associated with a lower risk of cognitive impairment in
later life in the Chinese population (26). However, a recent meta-analysis evidenced
conflicting results on cognitive outcomes of B-vitamin supplementations due to the great
variability of the existing trials in terms of type of supplementations, population sampled,
study quality, and duration of treatment (27).
Long chain polyunsaturated fatty acids (LC-PUFAs)
Neuronal cell membranes are particularly enriched in LC-PUFAs, important for the optimal
development and function of the brain and the nervous system (28). The two most important
types of LC-PUFAs in the human brain are eicosapentaenoic acid (EPA: 20:5 ω-3) and
docosahexaenoic acid (DHA: 22:6 ω-3) (29). Although different studies evidenced an
association between endogenous low levels of omega-3 and cognitive impairment and
Alzheimer’s disease (30, 31), the effects of ω-3 LC-PUFAs supplementation on cognitive
outcomes in randomized clinical trials remain controversial. In a randomized, double-blind,
placebo-controlled study, healthy older adults (62-80 years) with subjective memory
impairment receiving 2.4 g/d PUFAs for 24 weeks induced an increase in working memory
performance (32). The administration of DHA-enriched meals to subjects (n = 75; 88.5 ±
0.6 years) with cognitive impairment, living in nursing homes, protected against age-related
cognitive decline (33). On the other hand, in a recent very large trial involving 1680
participants, a daily dose of 800 mg DHA and 225 mg EPA had no significant effects on
cognitive decline over 3 years in elderly people aged 70 years or older with memory