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The impact of fruit flavonoids on memory and cognition
Jeremy P. E. Spencer
1,2
*
1
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG2 6AP, UK
2
Centre for Integrative Neuroscience and Neurodynamics, University of Reading, Reading RG2 6AP, UK
(Received 26 January 2010 – Revised 14 July 2010 – Accepted 20 July 2010)
There is intense interest in the studies related to the potential of phytochemical-rich foods to prevent age-related neurodegeneration and cognitive
decline. Recent evidence has indicated that a group of plant-derived compounds known as flavonoids may exert particularly powerful actions on
mammalian cognition and may reverse age-related declines in memory and learning. In particular, evidence suggests that foods rich in three
specific flavonoid sub-groups, the flavanols, anthocyanins and/or flavanones, possess the greatest potential to act on the cognitive processes.
This review will highlight the evidence for the actions of such flavonoids, found most commonly in fruits, such as apples, berries and citrus,
on cognitive behaviour and the underlying cellular architecture. Although the precise mechanisms by which these flavonoids act within the
brain remain unresolved, the present review focuses on their ability to protect vulnerable neurons and enhance the function of existing neuronal
structures, two processes known to be influenced by flavonoids and also known to underpin neuro-cognitive function. Most notably, we discuss
their selective interactions with protein kinase and lipid kinase signalling cascades (i.e. phosphoinositide-3 kinase/Akt and mitogen-activated pro-
tein kinase pathways), which regulate transcription factors and gene expression involved in both synaptic plasticity and cerebrovascular blood flow.
Overall, the review attempts to provide an initial insight into the potential impact of regular flavonoid-rich fruit consumption on normal or abnor-
mal deteriorations in cognitive performance.
Ageing is associated with many common chronic neuro-
degenerative diseases and the precise cause of the neuronal
degeneration underlying these disease and, indeed, normal
brain ageing remains unclear. It is thought that several cellular
and molecular events are involved, including increases in
oxidative stress, impaired mitochondria function, activation of
neuronal apoptosis, the deposition of aggregated proteins
and excitotoxicity. Thus far, the majority of existing drug treat-
ments for the treatment of neurodegenerative disorders are
unable to prevent the underlying degeneration of neurons and
consequently there is a desire to develop alternative therapies
capable of preventing the progressive loss of specific neuronal
populations. Since the neuropathology of many neurodegenera-
tive diseases has been linked to increases in brain oxidative
stress, historically, strong efforts have been directed at explor-
ing the antioxidant strategies to combat neuronal damage.
Indeed, there has been intense interest in the neuroprotective
effects of a group of plant secondary metabolites known as poly-
phenols, which are powerful antioxidants in vitro. A large
number of dietary intervention studies in human subjects
(1)
and animals
(2)
, in particular those using foods and beverages
derived from Vitis vinifera (grape), Camellia sinensis (tea),
Theobroma cacao (cocoa) and Vaccinium spp. (blueberry),
have demonstrated beneficial effects on human vascular
function and on improving memory and learning
(2 – 13)
. While
such foods and beverages differ greatly in chemical compo-
sition, macronutrient and micronutrient content and energy
load/serving, they have in common that they are among the
major dietary sources of a group of phytochemicals called
flavonoids (for review on source, structure and bioavailability,
refer to Spencer et al. and Rice-Evans et al.
(14,15)
).
Evidence has begun to emerge that these low molecular
weight, non-nutrient components may be responsible for the
beneficial effects of flavonoid-rich foods in vivo, through
their ability to directly or indirectly interact with the brain’s
innate architecture for memory
(16,17)
. Historically, the biologi-
cal actions of flavonoids on the brain were attributed to their
ability to exert antioxidant actions
(15)
, through their ability
to scavenge reactive species or through their possible influ-
ences on intracellular redox status
(18)
. However, it is now
clear that this classical hydrogen-donating antioxidant activity
cannot account for the bioactivity of flavonoids in vivo, par-
ticularly in the brain, where they are found at only very low
concentrations
(19)
. Instead, it has been postulated that their
effects in the brain are mediated by an ability to protect vul-
nerable neurons, enhance existing neuronal function, stimulate
brain blood flow and induce neurogenesis
(6)
.In vitro work has
indicated that flavonoids and their physiological metabolites
are capable of inducing neuronal and glial signalling pathways
crucial in inducing synaptic plasticity
(20 – 22)
, but only at low
nanomolar concentrations
(23)
similar to that reported in the
brain
(16)
. However, their interaction with these pathways has
wider relevance, as these signalling pathways are also respon-
sible for determining the fate of neurons following exposure to
neurotoxins
(24)
and inflammatory mediators
(17)
and in control-
ling cerebrovascular blood flow. The present review examines
*Corresponding author: J. P. E. Spencer, email j.p.e.spencer@reading.ac.uk
Abbreviations: CBF, cerebral blood flow; DG, dentate gyrus.
British Journal of Nutrition (2010), 104, S40–S47 doi:10.1017/S0007114510003934
qThe Author 2010
British Journal of Nutrition
the potential for flavonoids and flavonoid-rich fruits to
influence brain function and the mechanisms that might be
responsible for such actions in the brain.
Modulation of memory and cognition by flavonoid-rich
fruits
A recent prospective study has provided strong evidence that
dietary flavonoid intake is associated with better cognitive
evolution, i.e. the preservation of cognitive performance
with ageing
(25)
. Furthermore, there is much evidence to
suggest that flavonoids found in fruits and fruit juices (most
notably flavanols, flavanones and anthocyanins) have the
capacity to improve memory
(6,19,26 – 28)
. A number of animal
intervention studies, using diets containing between 1 and
2 % (w/w) freeze-dried fruit/fruit juice, have indicated that
grape, pomegranate, strawberry and blueberry, as well as
pure flavonoids (epicatechin and quercetin), are capable of
affecting several aspects of memory and learning, notably
rapid
(11)
and slow
(29 – 32)
memory acquisition, short-term
working memory
(16,33 – 36)
, long-term reference memory
(9,37)
,
reversal learning
(11,33)
and memory retention/retrieval
(38)
.
For example, fruits such as strawberry, blueberry and black-
berry (all rich in anthocyanins and flavanols) have been
shown to be beneficial in retarding functional, age-related
CNS and cognitive behavioural deficits
(29,39,40)
. There is also
extensive evidence that berries, most notably blueberries,
which are equally rich in both anthocyanin and flavanols,
are effective at reversing age-related deficits in spatial working
memory
(16,35,37,40 – 46)
. Furthermore, the effects of blueberry
and blackberry appear to be most pronounced in terms of
short-term memory, suggesting that these improvements are,
in part, dependent on CA3 –CA3 excitatory connections in
the hippocampus
(40,47)
. Although it is presently uncertain as
to whether it is the flavonoids within these fruits which are
causal agents in inducing the behavioural effects, evidence
is beginning to emerge that suggests they are able to induce
both behavioural and related cellular changes. For example,
the flavanol (2)-epicatechin (500 mg/g), which is found in a
variety of fruits (apple, pear, grape and all berries), has been
shown to enhance the retention of rat spatial memory in
water maze tasks, especially when combined with exercise
(38)
.
This improvement was associated with increased angiogenesis
and neuronal spine density in the dentate gyrus (DG) of the
hippocampus and with the up-regulation of genes associated
with learning in the hippocampus.
Alternatively, the blueberry-derived flavonoids may act to
enhance the efficiency of spatial memory indirectly by
acting on the DG, the hippocampal sub-region most sensitive
to the effects of ageing
(48)
. DG granule cells are particularly
vulnerable to the ageing process
(49,50)
, with age-dependent
degeneration resulting in an impairment of information trans-
fer between DG and CA3, thus resulting in an inability of CA3
networks to build new spatial representations
(48)
. This is sup-
ported by observations that DG lesioned animals exhibit
marked difficulties in acquiring spatial representations
(51)
.
Blueberry supplementation has been shown to significantly
increase the proliferation of precursor cells in the DG of
aged rats
(37)
. This link between DG neurogenesis, cognitive
performance and ageing is well documented
(52 – 56)
and
may represent another mechanism by which fruits rich in
flavonoids may improve memory by acting on the hippo-
campus. Again, it is unclear at present whether flavonoids
themselves are wholly responsible for the effects of flavo-
noid-rich fruits in vivo and also whether they induce global
changes in hippocampal (and other brain region) mor-
phology/function or are they capable of more specific changes
in hippocampal sub-regions. In the next section, we examine
the known interactions of flavonoids with the cellular struc-
tures and processes involved in normal brain function in an
attempt to better understand how these actions might underpin
the wide range of beneficial actions of flavonoid-rich fruits on
mammalian cognitive processing.
Mechanisms of action
There is now much evidence to suggest that fruit-derived phy-
tochemicals, in particular flavonoids, are capable of promoting
beneficial effects on memory and learning
(16,26,29,39,43,57 – 59)
.
It appears that they are able to impact upon memory through
their ability to exert effects directly on the brain’s innate
architecture for memory
(6)
. This cellular architecture is well
known to deteriorate with ageing with neuronal populations
or synaptic connections lost over time, leaving the system
less efficient in the processing and storage of sensory
information. The next three sections describe how specific
flavonoids or flavonoid-rich fruits impact upon this innate
cellular architecture and thereby influence cognitive proces-
sing and ultimately behavioural outcomes such as memory.
Interaction with neuronal signalling and synaptic function
The ability of flavonoids to impact upon memory appears to
be, in part, underpinned by their ability to interact with the
molecular and physiological apparatus used in normal
memory processing
(21,60)
. The concentrations of flavonoids
and their metabolites that reach the brain following dietary
supplementation are believed to be in the region of
10 –300 nm. Such concentrations are sufficiently high to exert
pharmacological activity at receptors, kinases and transcription
factors
(20)
. Although the precise site of their interaction
with signalling pathways remains unresolved, evidence
indicates that they are capable of acting in a number of ways:
(1) by binding to ATP sites on enzymes and receptors; (2) by
modulating the activity of kinases directly, i.e. MAPKKK,
MAPKK or MAPK; (3) by affecting the function of important
phosphatases, which act in opposition to kinases; (4) by modu-
lating transcription factor activation and binding to promoter
sequences, i.e. cyclicAMP-response element-binding protein
(reviewed in Spencer
(21,61)
) (Fig. 1).
Flavonoids and flavonoid-rich fruits are well reported to
modulate neuronal signalling pathways crucial in inducing
synaptic plasticity
(21)
, in particular with the extracellular
receptor kinase and protein kinase B/Akt pathways
(61 – 63)
.
The activation of these pathways has been observed in vivo
following dietary intervention with blueberry (2 % (w/w)
freeze-dried blueberry), along with the activation of the tran-
scription factor cyclicAMP-response element-binding protein
and production of neurotrophins such as brain-derived neuro-
trophic factor, which are known to be required during
memory acquisition and consolidation. Agents, both dietary
and otherwise, capable of inducing pathways leading to
Fruit flavonoids and cognition S41
British Journal of Nutrition
cyclicAMP-response element-binding protein activation are
believed to have the potential to enhance both short-term
and long-term memories
(16)
, through the initiation of processes
leading to the generation of a more efficient structure for inter-
preting afferent nerve or sensory information. One mechanism
by which this may come about is through flavonoid-induced
increases in neuronal spine density and morphology, two fac-
tors considered vital for learning and memory
(64)
.
Changes in spine density, morphology and motility have
been shown to occur with paradigms that induce synaptic, as
well as altered sensory experience, and lead to alterations in
synaptic connectivity and strength between neuronal partners,
which ultimately affects the efficacy of synaptic communi-
cation (Fig. 1). In support of this, dietary supplementation
with blueberries rich in both high flavanol and anthocyanin
has been shown to cause activation of mammalian target of
rapamycin and an increased expression of hippocampal Arc/
Arg3·1
(16)
, events which are likely to facilitate changes in
synaptic strength through the stimulation of the growth of
small dendritic spines into large mushroom-shaped spines.
The ability of flavonoids to induce such morphological
changes through interactions with neuronal signalling is sup-
ported by studies which have shown that specific flavanols
are capable of inducing neuronal dendrite outgrowth
(65)
. Fur-
thermore, nobiletin, a poly-methoxylated flavone found in
citrus peel, also induces neurite outgrowth
(66)
and synaptic
transmission
(67)
via its ability to interact directly with mito-
gen-activated protein kinase and PKA signalling pathways,
while its metabolite, 40-demethylnobiletin, exerts similar
effects via the same pathways
(68)
. While these effects are
interesting, and in agreement with previous observations
with flavonoids, it should be noted that they were observed
at concentrations ranging from 10 to 100 mM, which are unli-
kely to be achieved in the brain.
Influence on blood flow and neurogenesis
There is also evidence to suggest that flavonoid-rich foods
may be capable of preventing many forms of cerebrovascular
disease including those associated with stroke and demen-
tia
(69,70)
. It is thought that flavonoids meditate these effects
in vivo through their potential to affect endothelial function
and peripheral blood flow
(71)
. Such vascular effects are poten-
tially significant as increased cerebrovascular function is
known to facilitate adult neurogenesis in the hippocampus
(72)
(Fig. 1). Indeed, new hippocampal cells are clustered near
blood vessels, which proliferate in response to vascular
growth factors and may influence memory
(73)
. Efficient cer-
ebral blood flow (CBF) is vital for optimal brain function,
with several studies indicating that there is a decrease in
CBF in patients with dementia
(74,75)
. Brain imaging tech-
niques, such as ‘functional MRI’ and ‘trans-cranial Doppler
ultrasound’, have shown that there is a correlation between
CBF and cognitive function in human subjects
(75)
. For
example, CBF velocity is significantly lower in patients with
Alzheimer disease and low CBF is also associated with incipi-
ent markers of dementia. In contrast, non-demented subjects
with higher CBF were less likely to develop dementia.
In this context, flavanol-rich foods have been shown to
cause significantly increased CBF in human subjects, 1–2 h
postintervention
(76,77)
. Although requiring further investi-
gation, intervention with a flavanol-rich drink derived from
cocoa (400– 900 mg flavanols) resulted inan acute (2h postinter-
vention) increase in blood flow (blood oxygen level-dependent
functionalMRI) in certain regions of the brain, along with a
modification of the blood oxygen level-dependent response
in individuals completing a ‘task switching’ test. Furthermore,
‘arterial spin-labelling sequence MRI’
(78)
also indicated that
cocoa flavanols increase CBF up to a maximum of 2 h after
Flavonoids
Inhibition Activation
ERK1/2, Akt/PKBJNK1/2/3, p38, ASK1
STAT-1, c-jun
iNOS, NO Bad, BclxL, Caspases BDNF, NRF, Arc mTOR, VEGF-B, TGF-β
CREB
Neuroinflammation
Prevention of neurodegeneration
and brain ageing Enhancement of memory and cognition
Suppression of microglia
Reduction in NO production
TNF-α reduced
Inhibition of apoptosis
Neuronal survival
Expression of survival
proteins
Dendritic spine growth
Neuronal communication
Synaptic plasticity
Increased blood flow
Angiogenesis
New nerve cell growth
Neuronal viability Neuronal morphology Vascular effects
Fig. 1. Flavonoid-induced activation and inhibition of neuronal and glial signalling and functional implications. Activation of extracellular receptor kinase (ERK),
Akt and cyclicAMP-response element-binding protein (CREB) by flavonoids may promote changes in synaptic plasticity and neurogenesis, which ultimately
influence memory, learning and cognition. Activation of these pathways may also lead to the inhibition of pro-apoptotic signalling in neurons (bad and caspases).
Flavonoid-induced inhibition of the c-jun N-terminal kinases (JNK), apoptosis signal-regulating kinase-1 and p38 pathways leads to an inhibition of both the
apoptosis in neurons and a reduction of neuroinflammatory reactions in microglia (reduction in inductible nitric oxide synthase (iNOS) expression and NOzrelease).
PKB, protein kinase B; mTOR, mammalian target of rapamycin; STAT-1, signal transducers and activators of transcription family-1; c-jun, c-jun N-terminal
kinases; NO, nitric oxide; BDNF, brain-derived neurotrophic factor; VEGF, vascular endothelial growth factor; TGF, tumour growth factor.
J. P. E. SpencerS42
British Journal of Nutrition
ingestion of the flavanol-rich drink. In support of these
findings, an increase in CBF through the middle cerebral
artery has been reported after the consumption of flavanol-rich
cocoa using trans-cranial Doppler ultrasound
(77)
. Clearly,
further investigation is required before one can be certain of
the full impact of flavonoids-rich foods on brain blood flow.
At present, there is very little information regarding the ability
of other flavonoid-rich foods, including effect of fruits on
cerebrovascular blood flow. However, if such responses
are ultimately dependent on the actions of flavanols on the
vascular system, as has been suggested
(71)
, then there is
good reason to hypothesise that other flavanol-rich foods,
such as apple, grape, blackcurrant and pear, may also possess
similar activity.
Inhibition of neurodegeneration and neuroinflammation
The underlying neurodegeneration observed in Parkinson’s,
Alzheimer’s and other neurodegenerative diseases is believed
to be triggered by multi-factorial processes, including neuroin-
flammation
(79,80)
, glutamatergic excitotoxicity and increases in
Fe and/or depletion of endogenous antioxidants
(81 – 83)
. There
is a growing body of evidence to suggest that flavonoids and
flavonoid-rich foods may be capable of counteracting such
neuronal injury, thereby delaying the progression of disease
pathologies
(19,22,61,84)
. The death of nigral neurons in
Parkinson’s disease is thought to involve the formation of the
endogenous neurotoxin, 5-S-cysteinyl-dopamine and its
oxidation product, dihydrobenzothiazine-1
(5,85 – 87)
. However,
the generation of 5-S-cysteinyl-dopamine
(88)
and resulting
neuronal injury induced by it are effectively counteracted by a
range of flavonoids and other polyphenols found commonly in
a range of fruits such as orange, berries, apple and grape
(5)
.
There is also evidence that flavanols and their metabolites are
effective in blocking oxidant-induced neuronal injury
(89,90)
at
concentrations relevant to those observed in vivo and in the
brain (typically 10 – 300 nm), through their ability to modulate
PI3 kinase (PI3K)/Akt and mitogen-activated protein kinase
signalling
(20,61)
. For example, the flavanols epicatechin and
30-O-methyl-epicatechin (100 and 300 nm) protect neurons
against oxidative damage via a mechanism involving the
suppression of c-jun N-terminal kinases, and downstream
partners, c-jun and pro-caspase-3
(91)
(Fig. 1). Similarly, the
citrus flavanones, hesperetin and its metabolite, 5-nitro-hesperetin
(10 –300 nm), inhibit oxidant-induced neuronal apoptosis via
a mechanism involving the activation/phosphorylation of
signalling proteins important in the pro-survival pathways
(92)
.
Recent evidence suggests that non-steroidal, anti-inflammatory
drugs are effective in delaying the onset of neurodegenerative
disorders, particularly Parkinson’s disease
(93)
. As such, there
has been an interest in the development of new compounds
with an ability to counteract neuroinflammatory injury to
the brain. The citrus flavanone naringenin (300 nm) has
recently been found to be highly effective in reducing lipopo-
lysaccharide/interferon-g-induced glial-cell activation and
resulting neuronal injury, via inhibition of p38 and signal
transducers and activators of transcription family-1, and a
reduction in inductible nitric oxide synthase expression and
other flavonoids has been shown to partially alleviate neuroin-
flammation through the inhibition of TNF-aproduction
(94)
(Fig. 1). Flavonoids present in blueberry have also been
shown to inhibit NOz, IL-1band TNF-aproduction in
activated microglia cells
(95)
, while the flavonol quercetin
(1 –30 mM)
(96)
and the flavanols catechin and epigallocatechin
gallate (1 –50 mM)
(97)
have all been shown to attenuate micro-
glia- and/or astrocyte-mediated neuroinflammation. As with
their activity against oxidative stress, their ability to exert
such actions appears to rely on their ability to directly modu-
late kinase signalling pathways, pro-inflammatory transcrip-
tion factors and the downstream regulation of inductible
nitric oxide synthase and cyclooxygenase-2 expression,
NOzproduction, cytokine release and NADPH oxidase
activation
(20,21,61,98)
. For example, flavonol fisetin (1 mM),
which is found in strawberry and other fruits, has been
shown to inhibit p38 mitogen-activated protein kinase
phosphorylation in LPS-stimulated BV-2 microglial cells
(99)
and the flavone luteolin (5 – 50 mM) inhibits IL-6 production
in activated microglia via inhibition of the c-jun N-terminal
kinases signalling pathway
(100)
.
Summary and future horizons
The actions of flavonoid-rich fruits and the specific flavonoids
that they contain on brain function appear to express signifi-
cant similarity. This suggests that the ability of many fruits
to exert effects on cognition appears to be underpinned by
their flavonoid content and involves a number of effects,
including a potential to protect neurons against injury induced
by neurotoxins and neuroinflammation, a potential to activate
synaptic signalling and an ability to improve cerebrovascular
blood flow. These effects appear to be mediated by the inter-
action of flavonoids and their physiological metabolites with
cellular signalling cascades in the brain and the periphery,
leading to an inhibition of apoptosis triggered by neurotoxic
species, the promotion of neuronal survival and differentiation
and an enhancement of peripheral and cerebral blood per-
fusion. Such effects induce beneficial changes in the cellular
architecture required for cognition and consequently provide
the brain with a more efficient structure for interpreting
afferent nerve or sensory information and for the storage,
processing and retrieval of memory. Furthermore, such
interactions also protect the brain against neuronal losses
associated with ageing, something which is particularly
relevant as this innate brain structure is known to deteriorate
with ageing, with neuronal populations or synaptic connec-
tions lost over time, leaving the system less efficient in its
ability to process sensory information.
The consumption of flavonoid-rich fruits, such as berries,
apple and citrus, throughout life may have the potential to
limit or even reverse age-dependent deteriorations in
memory and cognition. However, there are a number of ques-
tions still to be resolved. Most notably, at present, there is no
data in support of a causal relationship between the consumption
of flavonoids and behavioural outcomes in human subjects.
In order to make such relationships, future intervention
studies will be required to utilise better-characterised interven-
tion materials, more appropriate controls and more rigorous
clinical outcomes. While cognitive behavioural testing in
human subjects and animals provides an appropriate way of
assessing function, in vivo structural and dynamic quantitative
assessments will ultimately be required to provide hard
evidence of effects in the brain. For example, it would be
Fruit flavonoids and cognition S43
British Journal of Nutrition
highly advantageous to directly link behavioural responses to
changes in hippocampal volume and density, changes in
neural stem cell and progenitor cells and alterations in brain
blood flow using MRI and functional MRI techniques. Func-
tional MRI measures may be used to assess changes in
blood flow that underlie improved cognitive functioning as a
result of flavonoid-rich fruit supplementation. In addition,
such haemodynamic changes may be further compared with
changes in grey matter density and with biomarkers of
neural stem and progenitor cells, using proton NMR spec-
troscopy. Such an approach will be essential to provide links
between flavonoid intake and brain function in a mechanistic,
dynamic and quantitative way. Taking such an approach, one
may also be able to assess other factors relating to intake such
as the timeframe required to gain maximum beneficial effects,
the flavonoids most effective in inducing these changes and
the doses at which these become effective?
Furthermore, it appears that the precise mechanism by
which flavonoids act on cognitive performance appears to be
dependent on the period of flavonoid exposure. At present,
improvements in cognition resulting from acute dietary flavo-
noid-rich fruit interventions are thought to be dependent on
increased cerebrovascular blood flow. However, in vitro
studies using physiological doses of flavonoids have shown
that they are able to rapidly stimulate neuronal signalling path-
ways involved in cognitive processing and thus even acute
changes in cognition may be partly mediated by their direct
actions on neurons. In order to resolve this issue, further
studies are necessary to clearly resolve the issue of whether
flavonoids are able to localise in the brain following the con-
sumption of flavonoid-rich fruits. In human subjects, this can
only be resolved by the use of brain imaging technologies
allied to intervention studies utilising
13
C-labelled flavonoids
(either pure
13
C-labelled flavonoids or with fruits harvested
from plants grown in a
13
CO
2
environment). Cognitive
changes associated with long-term intake of fruit flavonoids
are more likely to involve morphological changes triggered
by the direct actions of flavonoids on neuronal signalling.
However, the extent to which daily acute changes in brain
blood flow impact upon such changes are presently
unknown. Thus, future studies are necessary and should be
designed to resolve the precise temporal nature of their
effects on memory as well as other issues, such as when one
needs to start consuming flavonoids to gain the maximum
beneficial effects?
Finally, the potential impact of diet on health care costs
should not be ignored. Dementia costs to the UK alone have
been estimated to be £17 billion/annum. If scientists could
develop a treatment that would reduce severe cognitive
impairment in older people by just 1 % per year, this would
cancel out all estimated increases in the long-term care costs
due to our ageing population (Alzheimer’s Research Trust).
Beyond this, there is also intense interest in the development
of drugs capable of enhancing memory and learning, both in
adults and in children, and there is a strong possibility that
in the future, specific nutrients, in particular fruit-derived fla-
vonoids, might act as precursors for the development of a new
generation of memory-enhancing drugs. As such, the present
series of reviews in this issue are extremely timely one and
highlight the present thinking in the field and outline the
future directions for research in the area.
Acknowledgements
J. P. E. S. is funded by the Biotechnology and Biological
Sciences Research Council (BB/F008953/1; BB/E023185/1;
BB/G005702/1), the FSA (FLAVURS) and the European
Union (FP7 FLAVIOLA). There is no conflict of interest
that I should disclose, having read the Journals guidelines.
J. P. E. S. is the sole author of the manuscript.
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