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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
*, Tiffany A. Nash
, Marcelle D. Shidler
, Barbara Shukitt-Hale
and James A. Joseph
Department of Psychiatry, University of Cincinnati Academic Health Center, Cincinnati, OH, USA
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
. Alzheimer’s disease comprises 60 to 80 % of
cases of dementia
. The construct mild cognitive impair-
identifies individuals with elevated risk for demen-
, and progression from mild cognitive impairment to
Alzheimer’s disease can be as high as 10 % per year
Further, there are indications that even age-associated
memory impairment, originally conceptualised as benign
, 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
, and
longitudinal investigation has shown a trebling of risk for
those categorised as having age-associated memory impair-
. 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
Regulation of inflammation generally is reduced with
, and accelerated inflammation is implicated in
neurodegenerative disorders such as Alzheimer’s disease
Berry fruits contain polyphenol compounds, which have
anti-inflammatory and antioxidant properties
. Polyphenols
also induce neuroprotective effects and influence neuronal
signalling involved in memory function
(14 – 16)
, and specific
constituents of grape juice have exhibited neuroprotective
Concord grape juice contains a variety of flavonoids and
antioxidants, among them anthocyanins and proanthocyani-
and comparatively high levels of total phenolics
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
, and hippocampal dis-
tribution has been associated with behavioural enhancement in
animal supplementation studies
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
, improved endothelial
and reduced platelet aggregation
. Such findings
are pertinent with respect to age-related cognitive decline
because of the strong relationship between CVD and neurode-
(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
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
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.
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.
Prospective participants were assessed with structured inter-
view instruments to determine eligibility for study inclusion.
The Academic and Medical History Questionnaire
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
, 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
. 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
. 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
was administered
to assess verbal learning and retention, and the Spatial Paired
Associate Learning Test
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-
(42 – 44)
. We also assessed mood as a potential covariate
of the cognitive measures with the Geriatric Depression
. 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
. 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)
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
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.
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
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.
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
. 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
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
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
. And, it may be that consistent, moderate-term
consumption is necessary to achieve sufficient concentrations
in brain sites
. 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
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
. 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.
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.
1. Ferri CP, Prince M, Brayne C, et al. (2005) Global prevalence
of dementia: a Delphi consensus study. Lancet 366, 21122117.
2. Alzheimer’s Association (2008) 2008 Alzheimer’s disease facts
and figures. Alzheimers Dement 4, 110133.
3. Petersen RC (2004) Mild cognitive impairment as a diagnostic
entity. J Intern Med 256, 183194.
4. Chertkow H, Nasreddine A, Joanette Y, et al. (2007) Mild
cognitive impairment and cognitive impairment, no dementia:
part A, concepts and diagnosis. Alzheimers Dement 3, 266 282.
5. Mitchell AJ & Shiri-Feshki M (2009) Rate of progression of
mild cognitive impairment to dementia meta-analysis of 41
robust inception cohort studies. Acta Psychiatr Scand 119,
6. Crook TH, Bartus RT, Ferris SH, et al. (1986) Age-associated
memory impairment: proposed diagnostic criteria and measures
of clinical change. Dev Neuropsychol 2, 261 276.
7. Neilsen H, Lolk A & Kragh-Sorensen P (1998) Age-associated
memory impairment – pathological memory decline or normal
aging? Scand J Psychol 39, 3337.
8. Goldman WP & Morris JC (2001) Evidence that age-associated
memory impairment is not a normal variant of aging. Alzheimer
Dis Assoc Disord 15, 7279.
9. Reid LM & MacLullich AMJ (2006) Subjective memory
complaints and cognitive impairment in older people. Dement
Geriatr Cogn Disord 22, 471485.
10. Saykin AJ, Wishart HA, Rabin LA, et al. (2006) Older adults
with cognitive complaints show brain atrophy similar to that
of amnestic MCI. Neurology 76, 834842.
11. Cotman CW (2000) Homeostatic processes in brain aging: the
role of apoptosis, inflammation, and oxidative stress in regulat-
ing healthy neural circuitry in the aging brain. In The Aging
Mind: Opportunities in Cognitive Research, pp. 114 143
[P Stern and L Carstensen, editors]. Washington, DC: National
Academy Press.
12. Franceschi C, Capri M, Monti D, et al. (2007) Inflammaging
and anti-inflammaging: a systematic perspective on aging and
longevity emerged from studies in humans. Mech Ageing Dev
128, 92105.
13. Giunta B, Fernandez F, Nilolic WV, et al. (2008) Inflammaging
as a prodrome to Alzheimer’s disease. J Neuroinflammation 5,
14. Ishige K, Schubert D & Sagar Y (2001) Flavonoids protect
neuronal cells by three different mechanisms. Free Radic Biol
Med 30, 433446.
15. Joseph JA, Arendash G, Gordon M, et al. (2003) Blueberry
supplementation enhances signaling and prevents behavioral
deficits in an Alzheimer’s disease model. Nutr Neurosci 6,
16. Olszanecki R, Gebska A, Kozlovski VI, et al. (2002) Flavonoids
and nitric oxide synthase. J Physiol Pharm 53, 571 584.
17. Conte A, Pellegrini S & Tagliazucchi D (2003) Synergistic
protection of PC12 cells from b-amyloid toxicity by resveratrol
and catechin. Brain Res Bull 62, 2938.
18. O’Byrne DJ, Devaraj S, Grundy SM, et al. (2002) Comparison
of the antioxidant effects of Concord grape juice flavonoids and
Grape juice supplementation improves memory 733
British Journal of Nutrition
a-tocopherol on markers of oxidative stress in healthy adult.
Am J Clin Nutr 76, 13671374.
19. Rice-Evans CA, Miller NJ & Paganga G (1996) Structure
antioxidant activity relationships of flavonoids and phenolic
acids. Free Radic Biol Med 20, 933 956.
20. Mullin W, Marks SC & Crozier A (2007) Evaluation of
phenolic compounds in commercial fruit juices and fruit
drinks. J Agric Food Chem 55, 31483157.
21. Singh M, Arseneault M, Sanderson T, et al. (2008) Challenges
for research on polyphenols from foods in Alzheimer’s disease:
bioavailability, metabolism, and cellular and molecular mechan-
isms. J Agric Food Chem 56, 48554873.
22. Youdim KA, Shukitt-Hale B & Joseph JA (2004) Flavonoids
and the brain: interactions at the blood brain barrier and their
physiological effects on the central nervous system. Free
Radic Biol Med 37, 16831693.
23. Youdim KA, Qaiser MZ, Begley D, et al. (2004) Flavonoid
permeability across an in situ model of the blood brain barrier.
Free Radic Biol Med 36, 592 604.
24. Andres-Lacueva C, Shukitt-Hale B, Galli RL, et al. (2005)
Anthocyanins in aged blueberry-fed rats are found centrally
and may enhance memory. Nutr Neurosci 8, 111 120.
25. Williams CM, El Moshen MA, Vauzour D, et al. (2008)
Blueberry-induced changes in spatial working memory correlate
with changes in hippocampal CREB phosphorylation and
brain-derived neurotrophic factor (BDNF) levels. Free Radic
Biol Med 45, 295305.
26. Chou EJ, Keevil JG, Aeschlimann S, et al. (2001) Effect of
ingestion of purple grape juice on endothelial function in
patients with coronary heart disease. Am J Cardiol 88,
27. Freedman JE, Parker C, Li L, et al. (2001) Select flavonoids and
whole juice from purple grapes inhibit platelet function and
enhance nitric oxide release. Circulation 103, 2792 2798.
28. Kalaria RN (2000) The role of cerebral ischemia in Alzheimer’s
disease. Neurobiol Aging 21, 321330.
29. Rober AE, Garani Z, Alexandrov AV, et al. (2006) Interaction
of cardiovascular disease and neurodegeneration: transcranial
Doppler ultrasonography and Alzheimer’s disease. Neurol Res
28, 672–678.
30. Skoog I & Gustafson D (2003) Hypertension, hypertension-
clustering factors and Alzheimer’s disease. Neurol Res 25,
31. Swan FE, Carmelli D & La Rue A (1998) Systolic blood
pressure tracking over 25 to 30 years and cognitive performance
in older adults. Stroke 29, 23342340.
32. Dai Q, Bornstein AR, Wu Y, et al. (2006) Fruit and vegetable
juices and Alzheimer’s disease: The Kame Project. Am J Med
119, 751759.
33. Nurk E, Refsum H, Drevon CA, et al. (2009) Intake of
flavonoid-rich wine, tea and chocolate by elderly men and
women is associated with better cognitive test performance.
J Nutr 139, 120–127.
34. Letenneur L, Proust-Lima C, Le Gouge A, et al. (2007)
Flavonoid intake and cognitive decline over a 10-year period.
Am J Epidemiol 165, 13641371.
35. Shukitt-Hale B, Carey A, Simon L, et al. (2006) Effects of
Concord grape juice on cognitive and motor deficits in aging.
Nutrition 22, 295302.
36. Krikorian R, Zimmerman ME & Fleck DE (2004) Inhibitory con-
trol in obsessive-compulsive disorder. Brain Cogn 54, 257 259.
37. Hughes CP, Berg L, Danziger WL, et al. (1982) A new clinical
scale for the staging of dementia. Br J Psychiatry 140, 566–572.
38. Lynch CA, Walsh C, Blanco A, et al. (2006) The clinical
dementia rating sum of box score in mild dementia. Dement
Geriatr Cogn Disord 21, 4043.
39. Willis LM, Shukitt-Hale B & Joseph JA (2009) Recent
advances in berry supplementation and age-related cognitive
decline. Cur Opin Clin Nutr Metab Care 12, 9194.
40. Delis DC, Kramer JH, Kaplan E, et al. (2000) California
Verbal Learning Test, 2nd ed. San Antonio, TX: Psychological
41. Krikorian R (1996) Independence of verbal and spatial paired
associate learning. Brain Cogn 32, 219223.
42. Greenaway MC, Lacritz LH, Binegar D, et al. (2006) Patterns of
verbal memory performance in mild cognitive impairment,
Alzheimer’s disease, and normal aging. Cogn Behav Neurol
19, 7984.
43. Fowler KS, Saling MM, Conway EL, et al. (2001) Paired
associate performance in the early detection of DAT. J Int
Neuropsychol Soc 8, 58–71.
44. Sahakian B, Downes J, Eagger S, et al. (1990) Sparing of atten-
tional relative to mnemonic function in a subgroup of patients
with dementia of the Alzheimer’s type. Neuropsychologia 28,
45. Yesavage JA, Brink TL, Rose TL, et al. (1983) Development
and validation of a geriatric depresssion rating scale: a pre-
liminary report. J Psychiatr Res 17, 3749.
46. Sheeber LB, Sorensen ED & Howe SR (1996) Data analytic tech-
niques for treatment outcome studies with pretest/posttest
measurements: an extensive primer. J Psychiatr Res 30, 185 –199.
47. Cohen J (1988) Statistical Power Analysis for the Behavioral
Sciences, 2nd ed. New York: Lawrence Erlbaum Associates.
48. Olin JT, Schneider LS, Eaton EM, et al. (1992) The Geriatric
Depression Scale and the Beck Depression Inventory as screen-
ing instruments in an older adult outpatient population. Psychol
Assess 4, 190–192.
49. Griffin WS (2008) Perispinal etanercept: potential as an
Alzheimer therapeutic. J Neuroinflammation 5,3.
50. Tobinick EL & Gross H (2008) Rapid cognitive improvement in
Alzheimer’s disease following perispinal etanercept adminis-
tration. J Neuroinflammation 5,2.
51. Shukitt-Hale B, Lau FC & Joseph JA (2008) Berry fruit
supplementation and the aging brain. J Agric Food Chem 56,
52. Kalt W, Blumberg JB, McDonald JE, et al. (2008) Identification
of anthocyanins in the liver, eye, and brain of blueberry-fed
pigs. J Agric Food Chem 56, 705712.
53. Casadesus G, Shukitt-Hale B, Stellwagen HM, et al. (2004)
Modulation of hippocampal plasticity and cognitive behavior
by short-term blueberry supplementation in aged rats. Nutr
Neurosci 7, 309316.
54. Martineau LC, Couture A, Spoor D, et al. (2006) Anti-diabetic
properties of the Canadian lowbush blueberry Vaccinium
angustifolium Ait. Phytomedicine 13, 612 623.
55. Tsuda T (2008) Regulation of adipocyte function by antho-
cyanins: possibility of preventing the metabolic syndrome.
J Agric Food Chem 56, 642 646.
R. Krikorian et al.734
British Journal of Nutrition
... Among 16 included studies in this review ( 10 studies included healthy participants at baseline [41, 43-45, 47, 49, 51, 57, 58, 61], five studies included older people manifesting cognitive decline [46,48,52,59,60] and the remaining one study recruited diagnosed mild to moderate dementia [50]. ...
... Among the juice supplementations, three studies were accumulated under the groupings of grape juice with mean dosage of 408 ml/d containing173.4 mg, 173.4 mg and 167 mg anthocyanins respectively [43,59,60]; three were cherry juice including concentrate with mean dosage of 247 ml/d containing 138 mg anthocyanins, 320 mg anthocyanins, and 450 mg total polyphenols respectively [41,50,58], one was cranberry juice with 32 ounces/d (around 942 ml) containing 435 mg total polyphenols [44]. One was blueberry juice concentrate with 30 ml/d [45] containing 387 mg anthocyanidins and one was orange juice study with 500 ml/d containing 305 mg flavanones [57]. ...
... For grape powder supplementation, Calapai et al. reported better attention (P < 0.001); language (P < 0.05); immediate memory (P < 0.0001); delayed memory (P < 0.0001) and MMSE score (P < 0.001) compared to the control without providing effect sizes [51]; Lee et al. also reported better attention/working memory under the domain of executive function, as measured with WAIS-III Digit Span within the intervention group (P = 0.04) without providing effect sizes, no effect on mood as assessed by Hamilton Rating Scale (HRS) was shown [52]. recognition memory task) with a large effect size (Cohen's d = 1.0) and no effect on mood as assessed by GDS [59]; Krikorian et al. reported improved Paired Associate Learning (PAL) (P = 0.009), Word List Recall (P = 0.04) with a medium effect size (Cohen's d = 0.56) and trend for improving mood measured as reduced depressive symptoms (P = 0.08) [60]. ...
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Objectives The cognitive-protective effects related to the consumption of a variety of fruits are supported by several intervention studies. This systematic review and meta-analysis compared the magnitude of effects following chronic (≥1 week) consumption of frozen, freeze-dried powder including extracts and juices of fruits, covering berries, cherries and citrus, on cognition and mood in adults. Methods PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until February, 2021. Inclusion criteria were randomised controlled trials assessing memory, executive function, psychomotor speed, mood and mini mental state examination in adult participants ≥18 years of age. Cognition was tested by global or domain specific tasks. Results Out of 13,861 articles identified, 16 papers were included; 11 studies provided suitable data for meta-analysis. Fourteen studies reported improvement or trend for improvement in cognition, five studies assessed mood and one study supplementing grape juice found trend for mood improvement. From the meta-analysis, cherry juice supplementation was suggested to improve psychomotor speed by −0.37 of standardised mean difference (95% CI [−0.74, 0.01]) in reaction time ( P = 0.05). Conclusions The meta-analysis did not sufficiently support a role for fruits or fruit forms to improve cognition and mood.
... For example, dietary supplementation with blueberries has been shown to improve memory in older adults with age-related memory decline such as forgetfulness and prospective memory lapses [6]. Similarly, concord grape juice enhanced memory function in older adults with MCI [7]. Despite growing evidence suggesting a protective role of anthocyanins for cognitive function, usual dietary intake of people diagnosed with MCI has not been well studied, limiting understanding of the potential for therapeutic interventions in this group. ...
... Comprehensive Assessment of Prospective Memory questionnaire self-report (CAPM) [15] which assesses the frequency of memory lapses in activities of daily living (Part A) and the perceived reasons for forgetting (Part C); and the Depression Anxiety Stress Scale (DASS-21) 7 [16] which is a 21-item self-report instrument for measuring depression, anxiety and tension/stress. Participants completed 3-day food records following instructions from a dietitian. ...
Research on the role of dietary anthocyanins in preventing cognitive decline in older adults shows promise. This study investigated the association between usual anthocyanin intake and indices of memory and cognition in 40 older adults diagnosed with Mild Cognitive Impairment (MCI) that were recruited to a randomised clinical trial. It was hypothesised that daily anthocyanin intake would be similar to healthy older adults and that higher anthocyanin intake would be associated with better cognitive performance. Cognitive performance was assessed using a battery of tests including the Rey Auditory Verbal Learning Test (RAVLT). Dietary intake was assessed through 3-day food records and anthocyanin intake quantified using the PhenolExplorer food composition database. Multivariate linear regression compared differences in cognitive performance between higher (10mg or more/day) and lower consumers (less than 10mg/day). Overall, participants had low median intake of anthocyanins (5.3; IQR: 32.1 mg/day), with the lower consumer group eating negligible anthocyanins (median 0.13; IQR 1.5 mg/day), and the higher consumer group eating above the national average (median 35.5; IQR: 71.5 mg/day). On the RAVLT, the higher anthocyanin-consumer groups recalled a greater number of words after a short delay following a distracter task (B: 2.07, SE:0.93, 95%CI: 0.18-3.96, p=0.03) and longer-delay of 20 minutes (B: 2.68, SE: 1.11, 95%CI: 0.43-4.94, p=0.02); and forgot less words after a long delay of 20 minutes (B:-2.63, SE:0.63, 95%CI: -3.90 - -1.35, p<0.001). Further investigation of the protective role of usual consumption of dietary anthocyanins for memory and cognition in pathological and normal ageing appears warranted. Trial registration: This cross-sectional study utilizes baseline data from a randomised controlled trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001184268).
... The Concord grape is a dark purple to blue colored variety belonging to Vitis labrusca. The health-promoting properties of Concord grape have been reported as cardiovascular protection [4][5][6][7][8], neuroprotection [9,10], and antiaging [11,12] and antitumoral effects [13]. Compared to culinary grape products, grape-derived commercial products, such as grape seed extracts, grape seed oil, and grape powder (grape skin dietary fiber), are rapidly expanding in the marketplace as they can be classified as high-value-added nutraceuticals or cosmetics. ...
... Concord grape and its derivate products are rich in polyphenol compounds, especially flavonoids such as anthocyanins, which contribute to its distinct purple hue. The benefits of Concord grape polyphenol compounds have been reported by many researchers: consumption of Concord grape juice can improve memory in senior adults with cognitive impairment, due to its anti-inflammatory effect and influence on neuronal signaling [10,77]; mice fed with Concord grape juice showed better motor function and cognitive performance related to neuronal and behavioral defects in aging caused by accumulated oxidative stress and inflammation [12]; supplementation of Concord grape juice can help to reduce blood pressure in hypertensive patients [6]; consumption of grapes can reduce the risk of cardiovascular disease [78]; supplementation of 10 mL·kg −1 ·d −1 Concord grape juice can achieve the same level of antioxidant capacity and protection of low-density lipoprotein against oxidation as that obtained with 400 IU α-tocopherol/d supplementation in healthy adults, and significantly lower native plasma protein oxidation rate than that in α-tocopherol-treated group [79]. Results of total phenolic and total anthocyanin contents and total antioxidant activity of whole Concord puree samples are presented in Table 1. ...
High-pressure processing (HPP) is utilized for food preservation as it can ensure product safety at low temperatures, meeting consumers' demand for fresh-like and minimally processed products. The purpose of this study was to determine the effects of HPP (600 MPa, 3 min, 5 °C) and pasteurization by heat treatment (HT, 63 °C, 3 min) on the production of a novel whole Concord grape puree product (with skin and seeds, no waste), and the shelf-life of the puree under refrigerated storage (4 °C). Microbial load, physicochemical properties, phenolic content and antioxidant activity, composition and sensorial attributes of puree samples were evaluated. HPP- and HT-treated purees were microbiologically stable for at least 4 months under refrigeration, with less microbial growth and longer shelf life for HPP samples. HPP and HT samples had similar levels of phenolic contents and antioxidant activities throughout the 4-month refrigerated storage period, even though HPP retained >75% PPO and POD enzyme activities while those of HT were less than 25%. Inclusion of seeds in the puree product significantly increased the fiber, protein, total fatty acid, and linoleic acid contents. Sensory results showed that HPP-treated puree retained more fresh-like grape attributes, had better consistency, and showed significantly higher ratings in consumer overall liking, product ranking, and purchase intent than the HT puree (p < 0.05).
... (75) antimicrobial, and cardioprotective properties (58). They can prevent platelet aggregation, LDL, DNA (59), lipid, protein (53), and membrane damage oxidation (57), reduce adhesion molecule expression and limit inflammations (60), which block cellular events predisposing atherosclerosis (61), enhance the regulation of blood pressure and vascular reactivity, reduce serum cholesterol and triglycerides (60), and improve memory function in older adults (62). They also help to prevent obesity and diabetes by inhibiting specific enzymes (52). ...
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Nowadays, the sector of isotonic beverages has developed its market based on fruit juices that provide a sports drink with antioxidant and biological activities in addition to their principal role of rehydration and replacement of minerals and carbohydrates during physical exercise. Consumption of grape juice is increasing worldwide because of its sensory characteristics and nutritional value. It contains mainly water, sugars, organic acids, and phenolic compounds. Phenolic compounds play a major role in prevention of various diseases through their biological activities linked to antioxidant, anti-inflammation, anticancer, anti-aging, antimicrobial, and cardioprotective properties. Several studies have demonstrated that grape juice is able to improve performances of antioxidant activity, protect against oxidative damage, and reduce inflammation during sports activities. Polyphenol content also provides a great sensory profile, mainly color which is an important indicator for consumers when choosing beverage products. The contribution of grape juice through its nutritional value and sensory properties makes it an alternative for the development of a new isotonic drink that will be a novel and healthy product in the field of healthy beverages.
... In terms of more commonly consumed flavonoid-rich foods, intervention trials have shown that grape juice, blueberry, and cocoa intake results in positive effects on cognitive outcome measures (257,258,403), although there are studies that suggest no changes in neurophysiological effects (89). With respect to berries, there is a large body of animal behavioral evidence that supports the efficacy of flavonoids on memory and learning. ...
... Data from a long-term cohort study of a 19.7-year follow-up of 2801 participants indicated that the risk of developing Alzheimer's disease and related dementias was reduced in individuals whose diet was high in flavonoids (20). Additionally, clinical trials demonstrated that regular consumption of fruits, such as grapes, berries, and oranges, had positive effects on cognitive function in patients with mild cognitive impairment as well as in old, healthy people (21,22). Therefore, there is a general consensus that high fruit intake can improve or prevent cognitive decline, thus resulting in a growing interest in this area of research. ...
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Dietary interventions rich in fruits and vegetables in aging people can reverse or mitigate age-related cognitive declines, delay the onset of neurodegenerative diseases (NDDs), and provide long-term health dividends. The novel food, popularly known as "Acai", is a berry belonging to the Euterpe genus of tropical palms trees and natively found in South America. Euterpe oleracea has been given much attention among scientists due to its high antioxidant capacity compared to other fruits and berries. Additionally, acai pulp composition analysis found that it contains various biologically active phytochemicals. In this review, we focused on current evidence relating to acai berry neuroprotection mechanisms and its efficacy in preventing or reversing neurodegeneration and age-related cognitive decline. A number of studies have illustrated the potential neuroprotective properties of acai berries. They have shown that their chemical extracts have antioxidant and anti-inflammatory properties and maintain proteins, calcium homeostasis, and mitochondrial function. Moreover, acai berry extract offers other neuromodulatory mechanisms, including anticonvulsant, antidepressant, and anti-aging properties. This neuromodulation gives valuable insights into the acai pulp and its considerable pharmacological potential on critical brain areas involved in memory and cognition. The isolated chemical matrix of acai berries could be a new substitute in research for NDD medicine development. However, due to the limited number of investigations, there is a need for further efforts to establish studies that enable progressing to clinical trials to consequently prove and ratify the therapeutic potential of this berry for several incurable NDDs.
... In recent years, much research has been carried out to elucidate the benefits of plant derived polyphenols in treating neuropathological disorders, including Alzheimer's disease. There is certain evidence that suggests the pathophysiological effects of metabolic syndrome are successfully altered by the dietary intake of polyphenols [20,107,111,112]. For any therapeutic agent to be explored for treating the neurodegenerative disease, it should have the ability to cross the blood brain barrier. ...
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Dietary polyphenols encompass a diverse range of secondary metabolites found in nature, such as fruits, vegetables, herbal teas, wine, and cocoa products, etc. Structurally, they are either derivatives or isomers of phenol acid, isoflavonoids and possess hidden health promoting characteristics, such as antioxidative, anti-aging, anti-cancerous and many more. The use of such polyphenols in combating the neuropathological war raging in this generation is currently a hotly debated topic. Lately, Alzheimer’s disease (AD) is emerging as the most common neuropathological disease, destroying the livelihoods of millions in one way or another. Any therapeutic intervention to curtail its advancement in the generation to come has been in vain to date. Using dietary polyphenols to construct the barricade around it is going to be an effective strategy, taking into account their hidden potential to counter multifactorial events taking place under such pathology. Besides their strong antioxidant properties, naturally occurring polyphenols are reported to have neuroprotective effects by modulating the Aβ biogenesis pathway in Alzheimer’s disease. Thus, in this review, I am focusing on unlocking the hidden secrets of dietary polyphenols and their mechanistic advantages to fight the war with AD and related pathology.
... Plant-based foods, as well as beverages rich in flavonoids, have been shown to reduce age-related cognitive and motor decline in humans and in laboratory animals (Shukitt-Hale et al., 2006;Krikorian et al., 2010a;Krikorian et al., 2010b;Rendeiro et al., 2012;Shukitt-Hale et al., 2015). Specifically, improvements in balance and coordination in aged animals were observed with diets containing polyphenol-rich grape juice, blueberries, strawberries, blackberries, and walnuts (Shukitt-Hale et al., 2006;Joseph et al., 2009;Shukitt-Hale et al., 2009;Willis et al., 2009). ...
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Exercise and consumption of plant-based foods rich in polyphenols are attractive therapeutic approaches for the prevention and treatment of Parkinson’s disease (PD). Few studies, however, have examined the neuroprotective efficacy of combining these treatment modalities against PD. Therefore we investigated whether combining voluntary running and consumption of blueberry juice (BBJ) was more efficacious against 6-hydroxydopamine (6-OHDA) toxicity than either treatment alone. Four weeks of running before and after intrastriatal 6-OHDA reduced amphetamine-induced rotational behavior and loss of substantia nigra dopamine (DA) neurons. BBJ consumption alone had no ameliorative effects, but when combined with exercise, behavioral deficits and nigrostriatal DA neurodegeneration were reduced to a greater extent than exercise alone. The neuroprotection observed with exercise alone was associated with an increase in striatal glial cell-lined derived neurotrophic factor (GDNF), whereas combining exercise and BBJ was associated with an increase in nigral GDNF. These results suggest that polyphenols may potentiate the protective effects of exercise and that differential regulation of GDNF expression underlies protection observed with exercise alone versus combined treatment.
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The world is facing a rapid population ageing. Noncommunicable disorders (NCDs) form the bulk of present-day morbidity. Besides dealing with neurodegeneration and neurocognitive disorders, modern-day therapeutics have also geared toward healthy ageing and preventive approaches. Several chemical substances belonging to classes of natural dietary origin display protective properties against some age-related diseases, including neurodegenerative ones. These compounds, known as nutraceuticals, differ structurally, acting on different pathways. There has been a paradigm shift in the understanding of dementias toward neuroinflammation, oxidative stress, immunomodulation, and gut-brain axis dysregulation. This offers promise for the nutraceuticals as a novel approach in the field of neurocognitive disorders and healthy ageing. However, the collective evidence is still evolving and as of yet not robust enough for nutraceuticals to be a part of clinical guidelines. The other caveats are lack of subjective understanding of use, and individual constituents of a product showing differential effects, which lead to ambiguous outcomes in clinical trials. This chapter critically looks at the role of various nutraceuticals in promoting healthy aging and management of neurodegenerative conditions (especially Alzheimer’s disease). The evidence so far is highlighted with the challenges in their use and future directions of research.
Among mental health diseases, depression is a global problem with a high prevalence for elderly patients and is directly related to the nutritional status. Depression of older people is considered as a psychological phenomenon with consequences for nutrition, additionally nutrition disorder can conduce to psychological effects. Scientists have identified essential nutritional factors, which can lead in case of deficiency to depression. Among these nutritional factors, some water-soluble and fat-soluble vitamins, minerals, polyunsaturated fatty acids, polyphenols, as well as proteins were identified. This review highlights the relationship between balanced diets in elderly people and the risk of depression.
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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.
This report discusses the public health impact of Alzheimer’s disease (AD), including incidence and prevalence, mortality rates, costs of care and the overall effect on caregivers and society. It also examines the challenges encountered by health care providers when disclosing an AD diagnosis to patients and caregivers. An estimated 5.3 million Americans have AD; 5.1 million are age 65 years, and approximately 200,000 are age <65 years and have younger onset AD. By mid-century, the number of people living with AD in the United States is projected to grow by nearly 10 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops AD every 67 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year, and the estimated prevalence is expected to range from 11 million to 16 million. In 2013, official death certificates recorded 84,767 deaths from AD, making AD the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years. Between 2000 and 2013, deaths resulting from heart disease, stroke and prostate cancer decreased 14%, 23% and 11%, respectively, whereas deaths from AD increased 71%. The actual number of deaths to which AD contributes (or deaths with AD) is likely much larger than the number of deaths from AD recorded on death certificates. In 2015, an estimated 700,000 Americans age 65 years will die with AD, and many of them will die from complications caused by AD. In 2014, more than 15 million family members and other unpaid caregivers provided an estimated 17.9 billion hours of care to people with AD and other dementias, a contribution valued at more than $217 billion. Average per-person Medicare payments for services to beneficiaries age 65 years with AD and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2015 for health care, long-term care and hospice services for people age 65 years with dementia are expected to be $226 billion. Among people with a diagnosis of AD or another dementia, fewer than half report having been told of the diagnosis by their health care provider. Though the benefits of a prompt, clear and accurate disclosure of an AD diagnosis are recognized by the medical profession, improvements to the disclosure process are needed. These improvements may require stronger support systems for health care providers and their patients.
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.
Volgens rapport van de Wereld Gezondheidsorganisatie uit 2003 is de ziektelast van dementie hoger dan van welke andere aandoening dan ook. Zij brengt zeer hoge kosten met zich mee voor zowel de gezondheidszorg als de maatschappelijke dienstverlening en tevens door de grote behoefte aan institutionele zorg. Alzheimer Disease International, het overkoepelende orgaan van vele nationale Alzheimer organisaties, heeft een internationale groep van deskundigen bijeengeroepen om evidencebased ramingen te maken van de prevalentie van dementie in alle regio’s van de wereld voor nu en in de toekomst (2020- 2040).