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Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment

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Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular pathology in individuals with CVD, and consumption of such flavonoid-containing foods is associated with a reduced risk for dementia. In addition, preliminary animal data have indicated improvement in memory and motor function with grape juice supplementation, suggesting potential for cognitive benefit in ageing humans. In this initial investigation of neurocognitive effects, we enrolled twelve older adults with memory decline but not dementia in a randomised, placebo-controlled, double-blind trial with Concord grape juice supplementation for 12 weeks. We observed significant improvement in a measure of verbal learning and non-significant enhancement of verbal and spatial recall. There was no appreciable effect of the intervention on depressive symptoms and no effect on weight or waist circumference. A small increase in fasting insulin was observed for those consuming grape juice. These preliminary findings suggest that supplementation with Concord grape juice may enhance cognitive function for older adults with early memory decline and establish a basis for more comprehensive investigations to evaluate potential benefit and assess mechanisms of action.
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Concord grape juice supplementation improves memory function in older
adults with mild cognitive impairment
Robert Krikorian
1
*, Tiffany A. Nash
1
, Marcelle D. Shidler
1
, Barbara Shukitt-Hale
2
and James A. Joseph
2
1
Department of Psychiatry, University of Cincinnati Academic Health Center, Cincinnati, OH, USA
2
USDA Human Nutrition Research Center on Aging and Tufts University, Boston, MA, USA
(Received 1 May 2009 – Revised 3 September 2009 – Accepted 4 September 2009 – First published online 23 December 2009)
Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling.
Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular pathology in individuals with CVD,
and consumption of such flavonoid-containing foods is associated with a reduced risk for dementia. In addition, preliminary animal data have
indicated improvement in memory and motor function with grape juice supplementation, suggesting potential for cognitive benefit in ageing
humans. In this initial investigation of neurocognitive effects, we enrolled twelve older adults with memory decline but not dementia in a ran-
domised, placebo-controlled, double-blind trial with Concord grape juice supplementation for 12 weeks. We observed significant improvement in
a measure of verbal learning and non-significant enhancement of verbal and spatial recall. There was no appreciable effect of the intervention on
depressive symptoms and no effect on weight or waist circumference. A small increase in fasting insulin was observed for those consuming grape
juice. These preliminary findings suggest that supplementation with Concord grape juice may enhance cognitive function for older adults with
early memory decline and establish a basis for more comprehensive investigations to evaluate potential benefit and assess mechanisms of action.
Memory: Cognitive impairment: Elderly: Grape juice: Polyphenols
Worldwide dementia prevalence is almost 25 million cases
and is projected to reach more than 81 million cases by the
year 2040
(1)
. Alzheimer’s disease comprises 60 to 80 % of
cases of dementia
(2)
. The construct mild cognitive impair-
ment
(3)
identifies individuals with elevated risk for demen-
tia
(4)
, and progression from mild cognitive impairment to
Alzheimer’s disease can be as high as 10 % per year
(5)
.
Further, there are indications that even age-associated
memory impairment, originally conceptualised as benign
forgetfulness
(6,7)
, can reflect very early neurodegeneration.
Older adult samples with subjective memory complaints
who meet criteria for age-associated memory impairment
show degradation in the medial temporal lobe that is similar,
albeit not as extensive, as that observed in subjects with
mild cognitive impairment and Alzheimer’s disease
(8)
, and
longitudinal investigation has shown a trebling of risk for
those categorised as having age-associated memory impair-
ment
(9,10)
. Such findings imply that memory complaints and
associated manifestations in everyday functioning can be
meaningful indicators of neurodegeneration. Preventive inter-
ventions initiated when early memory decline is evident have
the potential to forestall progression, most likely at the final
stage when such treatment might be effective
(11)
.
Regulation of inflammation generally is reduced with
ageing
(12)
, and accelerated inflammation is implicated in
neurodegenerative disorders such as Alzheimer’s disease
(13)
.
Berry fruits contain polyphenol compounds, which have
anti-inflammatory and antioxidant properties
(14)
. Polyphenols
also induce neuroprotective effects and influence neuronal
signalling involved in memory function
(14 – 16)
, and specific
constituents of grape juice have exhibited neuroprotective
effects
(17)
.
Concord grape juice contains a variety of flavonoids and
antioxidants, among them anthocyanins and proanthocyani-
dins
(18,19)
and comparatively high levels of total phenolics
(20)
.
Information concerning flavonoid transport into the central
nervous system and absorption into brain tissue is emerging.
A number of recent studies have indicated that certain of
these compounds, in particular anthocyanins, cross the
bloodbrain barrier, although specific mechanisms have not
been established
(21 – 23)
. In addition, anthocyanins have been
identified in brain regions that mediate cognition, including
the medial temporal lobe and cortex
(24)
, and hippocampal dis-
tribution has been associated with behavioural enhancement in
animal supplementation studies
(24,25)
.
Human trials have shown that short- and moderate-term
supplementation with grape juice produces benefit in individ-
uals with CVD, including increased serum antioxidant
capacity and reduced LDL oxidation
(19)
, improved endothelial
function
(26)
and reduced platelet aggregation
(27)
. Such findings
are pertinent with respect to age-related cognitive decline
because of the strong relationship between CVD and neurode-
generation
(28 – 31)
. Epidemiological studies indicate that con-
sumption of fruits and vegetables is associated with lower
risk of neurodegenerative disorders and better cognitive per-
formance in the elderly
(32 – 34)
, and these effects have been
*Corresponding author: Dr Robert Krikorian, fax þ1 513 558 0877, email robert.krikorian@uc.edu
British Journal of Nutrition (2010), 103, 730–734 doi:10.1017/S0007114509992364
qThe Authors 2009
British Journal of Nutrition
attributed to the intake of a variety of flavonoid compounds
with antioxidant and anti-inflammatory properties. Recently,
a preliminary animal study demonstrated that ingestion of
Concord grape juice for 6 8 weeks induced enhancement of
cognitive performance in aged rodents
(35)
.
We sought to assess the effect of supplementation with
Concord grape juice on memory performance in older adults
with early age-related memory decline in a controlled trial
as an initial assessment of potential benefit in an at-risk
sample. We also obtained data on mood, anthropometrics
and metabolic parameters.
Methods
Participants
Participants were recruited from the general community with
newspaper advertising soliciting older adults with early
memory decline but not dementia for a dietary intervention
study. We enrolled twelve participants (eight men, four
women) with acquired memory changes such as forgetfulness
and prospective memory lapses. The mean age of the entire
sample was 78·2 (SD 5·0) years and the mean educational
level was 14·1 (SD 2·9) years.
Procedure
Prospective participants were assessed with structured inter-
view instruments to determine eligibility for study inclusion.
The Academic and Medical History Questionnaire
(36)
was
used to obtain demographic information and information
regarding academic attainment, current and past medical
conditions, and medication and substance use. Those with dia-
betes, substance-abuse disorder, or diagnosed psychiatric or
neurological condition were excluded. The level of memory
impairment was determined with the Clinical Dementia
Rating
(37)
, which elicits information from the participant and
an informant (typically, spouse or adult child) about the
nature and extent of cognitive decline as manifested in activi-
ties at home and in the community. The domains memory,
orientation, problem solving, community affairs, home activi-
ties and personal care were evaluated to determine a dementia
staging classification. Scores for each domain contributed to a
global Clinical Dementia Rating classification with the
memory domain weighted most heavily. Clinical Dementia
Rating classifications include no impairment, mild decline,
and mild, moderate and severe dementia. We enrolled individ-
uals with mild decline and excluded those with Clinical
Dementia Rating classifications indicating no impairment
and those with mild, moderate and severe dementia. A sum
of boxes score also was derived
(38)
. This score represented
the arithmetic sum of the category scores across the six
domains of functioning and served to quantify level of func-
tional decline.
Seven subjects were randomly assigned to receive the
placebo beverage and five were assigned to receive 100 %
Concord grape juice. Placebo and juice were provided for
the research by Welch Foods, Inc. (Concord, MA, USA).
The placebo beverage contained no juice or natural poly-
phenol but was formulated to look and taste like grape juice
and to have the same carbohydrate composition and energy
load (3·0 kJ/ml). The intervention involved 12 weeks of
daily consumption of juice or placebo with assessments at
pre-treatment baseline and during the final week of the inter-
vention. Previous human trials examining antioxidant effects,
endothelial function and cardioprotection in healthy subjects
and those with CVD used briefer interventions, of the order
of 24 weeks
(17,20 – 21)
. We chose a longer intervention
period because our outcomes concerned cognitive cerebral
function in older adults, and there are indications in pre-
clinical studies with other berry fruits that several weeks may
be required for accumulation in brain regions
(39)
. We instituted
a dosing schedule determined by body weight to maintain
daily consumption between 6 and 9 ml/kg, a range consistent
with other human grape juice trials
(17,20 – 21)
. Individuals
weighing 54 to 64 kg were prescribed 444ml/d, those weighing
between 65 and 76 kg consumed 532 ml/d, and those weighing
between 77 and 91 kg consumed 621 ml/d. Participants were
instructed to take daily quantities in equal, divided dosages
with the morning, midday and evening meals.
The primary outcomes were neurocognitive measures of
memory function administered before and after the interven-
tion. The California Verbal Learning Test
(40)
was administered
to assess verbal learning and retention, and the Spatial Paired
Associate Learning Test
(41)
was used to evaluate non-verbal
memory. The California Verbal Learning Test is a list-
learning and recall task, and the Spatial Paired Associate
Learning Test assesses memory for visual-spatial information
that is not amenable to verbal encoding. Both list-learning and
paired associate tasks have been used in the context of cogni-
tive ageing and dementia and are among the more sensitive
measures of memory decline associated with neurodegene-
ration
(42 – 44)
. We also assessed mood as a potential covariate
of the cognitive measures with the Geriatric Depression
Scale
(45)
. We performed weight and waist circumference
measures and obtained fasting blood samples for deter-
mination of serum glucose and insulin values.
Analyses of covariance were performed for each outcome
factor to isolate effects of the intervention while controlling
for individual differences
(46)
. The outcome score from the
final visit was the dependent measure and the corresponding
score from the baseline visit and the depressive symptom
score were covariate measures. We used eta squared values
to derive Cohen’s feffect size estimates, which are character-
ised as small (0·10), medium (0·25) and large (0·40)
(47)
.
Fig. 1. List acquisition performance assessing verbal learning on the
California Verbal Learning Test. Values are adjusted means, with standard
errors represented by vertical bars. Subjects consuming Concord grape juice
demonstrated significant improvement (F(1, 8) ¼5·55; P¼0·04; Cohen’s
f¼0·28).
Grape juice supplementation improves memory 731
British Journal of Nutrition
The present study was conducted according to the guide-
lines laid down in the Declaration of Helsinki and all
procedures involving human subjects were approved by the
University of Cincinnati Medical Institutional Review Board.
Written informed consent was obtained from all subjects.
Results
At pre-intervention baseline there was a modest, non-
significant difference for age between the groups (80 v. 75
years; t(10) ¼1·8; P¼0·10). There was no group difference
for educational level (13·4 v. 15·2 years; t(10) ¼1·02;
P¼0·32), index of functional impairment (Clinical Dementia
Rating sum of boxes score 1·0 v. 1·0; t(10) ¼0·0; P¼1·0),
weight (74·3 v. 79·4 kg; t(10) ¼1·04; P¼0·32) and waist
circumference (92·7 v. 96·7 cm; t(10) ¼0·81; P¼0·43).
There was a group difference for level of depressive
symptoms (Geriatric Depression Scale score 7·8 v. 3·0;
t(10) ¼2·19; P¼0·05), with greater depressive symptomology
among the placebo subjects. However, the symptom level
was not clinically elevated for either group
(48)
.
Both the juice and placebo beverage were generally well
tolerated, and there was no consistently reported adverse
effect. Discrete concerns included, for example, increased
frequency of urination associated with greater fluid
consumption and aversion to the taste of the juice or placebo
that developed over time.
As shown in Fig. 1, analysis of covariance demonstrated a
significant effect (P¼0·04) for item acquisition across learning
trials on the California Verbal Learning Test, indicating
improvement for subjects in the Concord grape juice group
relative to those receiving placebo. The effect size was mod-
erate (Cohen’s f¼0·28). Also, there were trends toward
improved performances for the grape juice subjects with
respect to delayed verbal recall (P¼0·10; Cohen’s f¼0·33)
and spatial memory (P¼0·12; Cohen’s f¼0·67), although
these were not statistically significant (Fig. 2).
There was no appreciable effect of the intervention on
depressive symptoms (adjusted Geriatric Depression Scale
scores 5·0 v. 7·2; F(1,8) ¼2·56; P¼0·14) and no effect on
weight (77·5 v. 77·8 kg, adjusted values; F(1, 8) ¼0·31;
P¼0·58) or waist circumference (94·9 v. 95·5 cm, adjusted
values; F(1, 8) ¼0·24; P¼063). Fasting glucose values were
not affected by the intervention (1011 v. 975 mg/l, adjusted
values; F(1, 8) ¼0·42; P¼0·53), but fasting insulin at
12 weeks was significantly elevated for the subjects consum-
ing grape juice (10·0 v. 13·7 mU/ml, adjusted values;
F(1, 8) ¼6·07; P¼0·03). Table 1 contains the unadjusted
mean scores for the outcome measures and shows the changes
in absolute values from the baseline to final assessment.
Discussion
In this preliminary study we sought to assess the effect of
moderate-term supplementation with 100 % Concord grape
juice on cognition in older adults with early memory decline
and found that memory function was improved with regular
grape juice consumption. To our knowledge, this is the first
controlled human trial examining neurocognitive response to
this dietary intervention, and our findings are consistent with
those of a recent animal study showing improvement in
cognitive performance with grape juice supplementation in
aged rodents
(35)
. Our data do not provide information as
to possible mechanisms leading to the beneficial effects.
However, given the existing body of research concerning
reductions of inflammatory and oxidative stress markers in
human subjects with CVD and lower risk of age-related
neurodegeneration with flavonoid consumption, these putative
mechanisms would be primary considerations.
Fig. 2. Delayed recall performance for verbal material on the California
Verbal Learning Test (F(1, 8) ¼3·37; P¼0·10; Cohen’s f¼0·35) and for
visual-spatial material on the Spatial Paired Associate task (F(1, 8) ¼3·23;
P¼0·12; Cohen’s f¼0·67). Subjects consumed either Concord grape juice
() or a placebo drink ( ). Values are adjusted means, with standard errors
represented by vertical bars.
Table 1. Unadjusted mean values for memory, mood, anthropometric and metabolic measures by group*
Placebo (n7) Concord grape juice (n5)
Baseline Final Difference Baseline Final Difference
CVLT learning 33·2 33·2 0·0 35·2 38·6 3·4
CVLT recall 5·4 5·0 20·4 6·0 7·2 1·2
S-PAL 2·4 2·0 20·4 2·8 4·5 1·7
GDS 7·8 7·2 20·6 3·0 5·0 2·0
Weight (kg) 74·3 74·9 0·6 79·4 80·4 1·0
Waist (cm) 92·7 93·0 0·3 96·7 97·5 0·8
Glucose (mg/l) 1002 999 23 915 987 72
Insulin (mU/ml) 11·9 11·1 20·8 9·6 12·6 3·0
CVLT, California Verbal Learning Test; S-PAL, Spatial Paired Associate Learning Test; GDS, Geriatric Depression Scale.
* Baseline refers to measures obtained at the pre-intervention assessment. Final refers to measures obtained during the
final week of the intervention. Difference ¼final score less baseline score.
R. Krikorian et al.732
British Journal of Nutrition
Recent preliminary data involving pharmaceutical TNF-a
inhibition have suggested that acute functional improvement
can be observed in patients with Alzheimer’s disease
(49,50)
,
indicating that suppression of a pro-inflammatory cytokine
can ameliorate mental decline even in patients with substan-
tially more advanced neurodegeneration than in our sample
of mild cognitive impairment subjects. Accordingly, consist-
ent application of a food product with anti-inflammatory
effects over a brief to moderate timeframe also might
be expected to induce cognitive cerebral enhancement,
especially in individuals with very early neurodegeneration.
Pre-clinical data indicating absorption of anthocyanins in
brain regions mediating cognition and associations with beha-
vioural indices of cognitive function
(24,25)
also would support
the notion that the demonstrated improvement in memory abil-
ity may reflect reduced inflammation and/or enhanced neural
function in response to the intervention. While it is not yet
clear to what extent and by what mechanism berry fruit con-
stituents cross the blood brain barrier, anthocyanins have
been identified in specific brain tissues even when not detected
in plasma
(51,52)
. And, it may be that consistent, moderate-term
consumption is necessary to achieve sufficient concentrations
in brain sites
(39)
. Further study of Concord grape juice
supplementation for greater duration with memory and inflam-
matory marker outcomes will be important. Other putative
mechanisms including reduction of oxidative stress and
enhanced neuronal signalling also merit investigation, as
these factors have been demonstrated to be important in
animal studies with blueberry supplementation
(53,54)
.
Our preliminary data indicated increased fasting insulin for
those who received grape juice in the absence of changes in
weight and waist circumference. This finding was unantici-
pated and is provocative given the matched carbohydrate
load in the placebo beverage and the fact that group
differences in metabolic parameters were not observed before
the intervention. It is possible that increased insulin secretion
was induced by constituents of the grape juice other than
sugars. There are data indicating that anthocyanins derived
from blueberries influence metabolic function, in particular
enhancing the actions of insulin
(54,55)
. It may be that similar
or related actions were induced in the present study, with con-
sistent grape juice consumption resulting in increased insulin
secretion. However, such notions are speculative, particularly
given the small scale of this preliminary trial. Certainly, this
issue warrants further investigation with respect to its reprodu-
cibility and the specific nature and basis for the effect.
The major limitation of the present study was the small
sample size, which limited power to detect differences.
However, the moderate to large effect sizes indicate that it
would be worthwhile to conduct larger trials to evaluate the
neurocognitive benefits and putative mechanisms of Concord
grape juice supplementation in pre-dementia conditions.
In view of the public health burden associated with neuro-
degeneration and Alzheimer’s disease, in particular, safe,
low-cost dietary interventions offer the possibility of inducing
substantial benefit.
Acknowledgements
Funding and material support was provided by Welch Foods,
Inc. (Concord, MA, USA).
R. K. conceived of the study and supervised the data
collection, analyses, interpretation and manuscript preparation.
T. A. N. and M. D. S. participated in data collection,
interpretation and manuscript preparation. B. S.-H. and
J. A. J. participated in manuscript preparation.
None of the authors has a financial interest in the supporting
company or the outcome of the research activity.
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... Various forms of fruit and vegetable intake have been explored in previous studies, for example, in the form of capsules [31,32], juices [33][34][35][36][37][38], powder [39][40][41], and frozen fruits [42]. Additionally, the efficacy of cognitive function was also measured by different cognitive tests. ...
... Additionally, the efficacy of cognitive function was also measured by different cognitive tests. For example, memory is measured by the California Verbal Learning Test (CVLT) [35], the Computerized Mental Performance Assessment System (COMPASS) [33], [25] the Visual Verbal Learning Test (VVLT) [36], the Spatial Paired Associate Learning Test [35], and the Visual Spatial Learning Test [36]. Furthermore, attention is also measured by different methods, e.g. the Stroop test [31,37,40,43], Frankfurt Attention Inventory [32], Trail Making Test [34,38], Auditory Odd Ball [40], Modified Attention Network Task [42], Auditory Continuous Performance Test [32], and COMPASS [33]. ...
... Additionally, the efficacy of cognitive function was also measured by different cognitive tests. For example, memory is measured by the California Verbal Learning Test (CVLT) [35], the Computerized Mental Performance Assessment System (COMPASS) [33], [25] the Visual Verbal Learning Test (VVLT) [36], the Spatial Paired Associate Learning Test [35], and the Visual Spatial Learning Test [36]. Furthermore, attention is also measured by different methods, e.g. the Stroop test [31,37,40,43], Frankfurt Attention Inventory [32], Trail Making Test [34,38], Auditory Odd Ball [40], Modified Attention Network Task [42], Auditory Continuous Performance Test [32], and COMPASS [33]. ...
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Background Memory and attention are important for daily functioning, and their function deteriorates due to aging. However, fruit and vegetable consumption are one of the protective factors against deterioration in memory and attention. This systematic review of randomized controlled trials (RCTs) aims to identify the effects of fruit and vegetable consumption on memory and attention. Methods We conducted a systematic search in EBSCOhost, ProQuest, PubMed, Embase, and Web of Science from inception up to 06/09/2022. The inclusion criteria were peer-reviewed articles, fruit and vegetable intake measured using randomized controlled trials, and the outcome measures that showed the results of memory and attention scores. Two researchers independently extracted articles that met the selection criteria and evaluated the quality of each study. Results There were 70 articles identified from the databases, of which 13 articles met the inclusion criteria and were included in this systematic review. There were 493 participants in total. The results show that consumption of fruit and vegetable intake improved memory and attention in longitudinal studies (10 to 12 weeks). Children showed improvement in immediate recall after supplementation with blueberries. Older adults required a higher dose of fruit and vegetable intake consumption to achieve significant improvement compared with children and younger adults. Furthermore, the effect of fruits and vegetables on memory showed better immediate memory recall than delayed recall. Conclusion This systematic review showed that there is an improvement in memory and attention with fruit and vegetable intake consumption. Hence, awareness of fruit and vegetable intake consumption is important to maintain cognitive health.
... Rich in polyphenols [1], particularly oligomeric proanthocyanidin complexes (OPCs), GSE has been extensively studied for its role in improving mental health and cognitive performance through various pharmacological mechanisms [2][3][4][5][6][7][8][9]. Moreover, several human clinical studies have demonstrated the efficacy of GSE in enhancing cognitive function and alleviating symptoms of low mood, further substantiating its potential health benefits [10][11][12][13][14][15][16]. ...
... The bioactive compounds in GSE, particularly OPCs, are known to exert neuroprotective effects [21], modulate neurotransmitter systems, and reduce oxidative stress and inflammation [22][23][24][25], which are critical factors in mood regulation and cognitive health. Additionally, GSE has demonstrated favorable safety and tolerability profiles in clinical studies [10][11][12][13][14][15][16], making it a promising alternative or complementary approach for managing low mood and related conditions. The extract utilized in the present research was a highly standardized grape seed extract (Enovita ® , referred to as GSEe herein) from Vitis vinifera L. rich in polyphenols, mainly composed of oligomeric proanthocyanidins, and also containing monomeric procyanidins (catechin and epicatechin). ...
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Background: Grape seed extract (GSE) from Vitis vinifera L. is rich in polyphenols and oligomeric proanthocyanidin complexes (OPCs), and it has shown potential benefits in managing low mood and cognitive function. In this study, we investigated the potential bioactivities of Enovita®, a standardized GSE extract (GSEe herein) rich in OPCs, in key mechanistic pathways related to low mood conditions and cognitive function. Methods: In vitro assays were conducted to assess GSEe's inhibitory effects on γ-aminobutyric acid transaminase (GABA-T) and monoamine oxidase A (MAO-A), its binding affinity to the GABA site of GABA-A receptors, and its effects on acetylcholinesterase (AChE). Its neuroprotective effects on human SH-SY5Y neuroblastoma cells under oxidative stress (induced by H2O2) were assessed using MTT and LDH release assays. Its antioxidant activities were evaluated using DPPH, ABTS, FRAP, ORAC, HORAC, total phenolic content, and TAS assays. Its cytotoxicity was also evaluated. Results: GSEe showed significant GABA-T inhibitory activity. It also exhibited MAO-A and AChE inhibition, along with moderate binding affinity to the GABA-A receptor. In neuroprotective assays, GSEe provided significant protection to SH-SY5Y cells against oxidative stress. GSEe demonstrated robust antioxidant activity in all assays, including scavenging of DPPH and ABTS radicals, high ferric-reducing power, high polyphenolic contents, and a substantial total antioxidant capacity. Conclusions: GSEe exhibits promising bioactivities, highlighting its potential as a supplement for modulating mood and enhancing cognitive function. Overall, the promising results from these in vitro studies provide a strong foundation for the continued exploration and development of GSEe as a viable natural supplement for enhancing mental health and cognitive function.
... The administration of blueberry ACNs improved spatial working memory in elderly Wistar rats and increased levels of brain-derived neurotrophic factor in the hippocampus, indicating a potential benefit for age-related cognitive decline [145]. Moreover, a study involving elderly individuals experiencing memory loss but without dementia revealed significant improvements in language learning abilities after 12 weeks of consuming ACNs-rich grape juice supplements [146]. An intervention study conducted with children aged 7 to 10 years involved administering either a placebo or a blueberry drink containing 15 or 30 g of freeze-dried wild blueberry powder. ...
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Long-term exposure to ultraviolet (UV) rays can result in skin photoaging, which is primarily characterized by dryness, roughness, pigmentation, and a loss of elasticity. However, the clinical drugs commonly employed to treat photoaged skin often induce adverse effects on the skin. Anthocyanins (ACNs) are water-soluble pigments occurring abundantly in various flowers, fruits, vegetables, and grains and exhibiting a range of biological activities. Studies have demonstrated that ACNs contribute to the repair of photoaged skin due to their diverse biological characteristics and minimal side effects. Evidence suggests that the stability of ACNs can be enhanced through encapsulation or combination with other substances to improve their bioavailability and permeability, ultimately augmenting their efficacy in repairing photoaged skin. A growing body of research utilizing cell lines, animal models, and clinical studies has produced compelling data demonstrating that ACNs mitigate skin photoaging by reducing oxidative stress, alleviating the inflammatory response, improving collagen synthesis, alleviating DNA damage, and inhibiting pigmentation. This review introduces sources of ACNs while systematically summarizing their application forms as well as mechanisms for repairing photoaged skin. Additionally, it explores the potential role of ACNs in developing functional foods. These findings may provide valuable insight into using ACNs as promising candidates for developing functional products aimed at repairing photoaged skin.
... Krikorian and colleagues conducted a randomized controlled trial and reported no significant difference in performance on the California Verbal Learning Test (CVLT) after 16 weeks of grape juice supplementation. 25 In another study, they reported significant improvements in a verbal paired-associate learning task after 12 weeks of blueberry juice supplementation. 26 However, both studies had small sample sizes, with the grape juice intervention group consisting of only 10 participants (total of 39 participants) and the blueberry juice intervention group having 9 participants (total of 40 participants). ...
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Background This study investigates the association between dietary flavonoid intake and the incidence of mild cognitive impairment (MCI) through a matched case-control design. Methods Dietary intake was assessed using a food frequency questionnaire, comparing the intake of flavonoids between individuals with MCI and those with normal cognitive function. Logistic regression analysis was employed to evaluate the correlation between dietary flavonoid intake and the risk of MCI. Additionally, blood concentrations of S100β, a marker of the blood-brain barrier (BBB) integrity, were measured using electrochemiluminescence immunoassay, and Pearson correlation analysis was conducted to explore the relationship between dietary flavonoid intake and blood S100β levels. Results Compared to participants with normal cognition, those with MCI had significantly lower dietary intakes of total flavonoids, isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, flavonols, and anthocyanidins, while the intake of peonidin was significantly higher. Univariate logistic regression analysis indicated that high dietary intake of total flavonoids, isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, and flavonols was negatively correlated with MCI, whereas peonidin intake was positively correlated with MCI. Multivariate logistic regression analysis confirmed these findings. Pearson correlation analysis revealed a significant negative correlation between dietary intake of kaempferol and myricetin and blood S100β levels. Conclusion Increasing the dietary intake of total flavonoids, isoflavones, daidzein, glycitein, genistein, and flavonols appears to be a protective factor against MCI, while higher intake of peonidin is associated with an increased risk of MCI. The protective or adverse effects of these flavonoids may not be related to the permeability of the BBB. Myricetin and kaempferol intake may protect cognitive function by maintaining BBB integrity.
... Clinical evidence-In 2009, Robert Krikorian and colleagues [125] conducted one of the first controlled human trials, demonstrating how the daily consumption of Concord grape juice (CGJ), an extract from grapes, could improve learning memory in older adults with early memory decline. These results were linked with greater fMRI activation in the anterior and posterior regions of the right hemisphere [33], a result linked to a greater hemodynamic response and increased neuronal activity due to CGJ supplementation [23,126,127]. ...
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Background: The aging population is associated with a net increase in the incidence and prevalence of chronic-degenerative diseases, particularly neurocognitive disorders. Therefore, the identification of preventative strategies to restrain the burden of such chronic conditions is of key relevance. Red wine and its components have accumulated evidence regarding their positive effects in terms of neurological pathologies associated with neurocognitive symptoms. Methods: Based on this background, the present narrative review aims to summarize the state-of-the-art evidence on the effects of red wine and its components on neurocognitive disorders in both preclinical and clinical settings. Results: The main findings highlight a protective effect of wine polyphenols present in red wine on dementia in different preclinical models of cognitive decline. The current translational clinical evidence remains uncertain, especially considering the risk-to-benefit ratio of alcohol consumption on brain health. Conclusions: Given the overall health risks associated with red wine consumption and consistent with the prevailing guidelines in the literature, there is insufficient evidence to support light-to-moderate red wine consumption as an effective strategy for preventing these diseases. However, the largely preclinical findings on polyphenols derived from red wine remain of significant interest in this context.
... Previous research has demonstrated that consuming blueberry or grape juice every day for a period of 12 weeks improved older volunteers' episodic memory abilities [19]. More recently, Bensalem et al. demonstrated that, after 8 weeks of supplementation, the combination of a polyphenol-rich grape and blueberry extract was able to prevent age-related memory decline in middle-aged mice (16 months old) [18]. ...
... Studies have found that aged mice can improve the plasticity and memory ability of their brains by eating concentrated polyphenols extracted from grapes and blueberries for 14 weeks (6). Previous studies have also found that drinking blueberry or grape juice rich in polyphenols for 12 weeks can improve the cognitive ability of elderly subjects with normal cognition (7,8). ...
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Introduction Some evidence suggests that fruit and alcohol consumption may be related to cognitive impairment. Methods This study conducted a cross-sectional study on the “correlation between eating habits and cognitive function of the middle-aged and elderly population in China.” The purpose of this study is to explore the relationship between fruit consumption, drinking habits and cognitive impairment in Chinese people over 50 years old. Results The results show that the protective factors of cognitive impairment are the preference for berries and the daily intake of 100-200 grams grapes in Chinese middle-aged and elderly people with objective cognitive unimpaired. The habit of drinking red wine is a protective factor for cognitive impairment in Chinese middle-aged and elderly people with mild cognitive impairment (MCI). However, this study did not find the relationship between white wine, beer, yellow rice wine, liquor and cognitive impairment. Discussion Therefore, we believe that berries, grapes and red wine consumption can protect the cognitive function of the middle-aged and elderly people in China, and the protective function is related to the basic cognitive state.
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This review explores the potential health benefits and applications of phenolic secoiridoids derived from olive oil by-products in the prevention of Alzheimer’s disease (AD). As reviewed herein, polyphenols, such as epigallocatechin-3-gallate, epicatechin, and resveratrol, show in vitro and in vivo antioxidant, anti-inflammatory, and neuroprotective properties, and are particularly relevant in the context of AD, a leading cause of dementia globally. The olive oil industry, particularly in the Mediterranean region, produces significant amounts of waste, including leaves, pomace, and wastewater, which pose environmental challenges but also offer an untapped source of bioactive compounds. Despite promising in vitro and in vivo studies indicating that olive-derived polyphenols, such as oleuropein and hydroxytyrosol, may mitigate AD pathology, human clinical trials remain limited. The variability in extraction methods and the complex nature of AD further complicate research. Future studies should focus on standardizing the protocols and conducting robust clinical trials to fully assess the therapeutic potential of these compounds. This approach not only supports the development of new treatments for AD but also promotes environmental sustainability by valorizing olive oil industry waste.
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Role of food supplement in management of brain diseases.
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This study investigated the independence of verbal and nonverbal memory processes in a nonclinical young adult sample using parallel procedures designed to elicit verbal and spatial paired associate learning, respectively. The data indicated that, in general, men performed better than women on the spatial learning task, although there was no difference on the verbal procedure. A hierarchical multiple regression analysis indicated that a configural attention measure was the best predictor of spatial learning, while performance on the verbal learning task contributed very little. These data support the notion that performance on genuinely material-specific memory tasks is largely independent and provide evidence of independent cognitive-cerebral processes.
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Alzheimer’s disease is the seventh leading cause of all deaths in the United States and the fifth leading cause of death in Americans older than the age of 65 years. More than 5 million Americans are estimated to have Alzheimer’s disease. Every 71 seconds someone in America develops Alzheimer’s disease; by 2050 it is expected to occur every 33 seconds. During the coming decades, baby boomers are projected to add 10 million people to these numbers. By 2050, the incidence of Alzheimer’s disease is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million persons. Significant cost implications related to Alzheimer’s disease and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (eg, caregiver lost wages and out-of-pocket expenses, decreased business productivity) costs. Not included in these figures are the estimated 10 million caregivers who annually provide $89 billion in unpaid services to individuals with Alzheimer’s disease. This report provides information to increase understanding of the public health impact of Alzheimer’s disease, including incidence and prevalence, mortality, lifetime risks, costs, and impact on family caregivers.
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