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Blueberry Supplementation Improves Memory in Older Adults


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The prevalence of dementia is increasing with expansion of the older adult population. In the absence of effective therapy, preventive approaches are essential to address this public health problem. Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects. In addition, anthocyanins have been associated with increased neuronal signaling in brain centers, mediating memory function as well as improved glucose disposal, benefits that would be expected to mitigate neurodegeneration. This study investigated the effects of daily consumption of wild blueberry juice in a sample of nine older adults with early memory changes. At 12 weeks, improved paired associate learning (p = 0.009) and word list recall (p = 0.04) were observed. In addition, there were trends suggesting reduced depressive symptoms (p = 0.08) and lower glucose levels (p = 0.10). We also compared the memory performances of the blueberry subjects with a demographically matched sample who consumed a berry placebo beverage in a companion trial of identical design and observed comparable results for paired associate learning. The findings of this preliminary study suggest that moderate-term blueberry supplementation can confer neurocognitive benefit and establish a basis for more comprehensive human trials to study preventive potential and neuronal mechanisms.
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Blueberry Supplementation Improves Memory in Older Adults
Department of Psychiatry, University of Cincinnati Academic Health Center, PO Box 670559,
Cincinnati, OH 45267-0559 USA
Agriculture & Agri-Food Canada, AFHRC, 32 Main Street, Kentville, Nova Scotia, B4N 1J5 Canada
§ USDA Human Nutrition Research Center on Aging and Tufts University, 711 Washington Street,
Boston, MA 02111-1524 USA
The prevalence of dementia is increasing with expansion of the older adult population. In the absence
of effective therapy, preventive approaches are essential to address this public health problem.
Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have
antioxidant and anti-inflammatory effects. In addition, anthocyanins have been associated with
increased neuronal signaling in brain centers mediating memory function as well as improved glucose
disposal, benefits that would be expected to mitigate neurodegeneration. We investigated the effects
of daily consumption of wild blueberry juice in a sample of nine older adults with early memory
changes. At 12 weeks, we observed improved paired associate learning (p = 0.009) and word list
recall (p = 0.04). In addition, there were trends suggesting reduced depressive symptoms (p = 0.08)
and lower glucose levels (p = 0.10). We also compared the memory performances of the blueberry
subjects with a demographically-matched sample who consumed a berry placebo beverage in a
companion trial of identical design and observed comparable results for paired associate learning.
The findings of this preliminary study suggest that moderate-term blueberry supplementation can
confer neurocognitive benefit and establish a basis for more comprehensive human trials to study
preventive potential and neuronal mechanisms.
blueberries; memory; metabolism; Mild Cognitive Impairment; prevention; neurodegeneration
Alzheimer’s disease (AD) accounts for 60% to 80% of cases of dementia (1). The prevalence
of AD threatens to reach epidemic proportions in the coming decades, with projections of 16
million cases in the US by 2050 (1). There are several age-related health conditions that increase
vulnerability to AD, most prominently cardiovascular risks (2). However, metabolic
disturbance appears to be a fundamental factor driving both cardiovascular disorders and
neurodegeneration (3). The presence of insulin resistance and diabetes increase risk for AD
substantially, and the risk attributable solely to hyperinsulinemia was determined to be as high
as 39% in one longitudinal study (4).
A number of concepts have been introduced to classify older adults at different stages of
cognitive decline. Mild Cognitive Impairment (MCI) identifies individuals with increased risk
*Tel: 513 558-4218; Fax: 513 558-0877;
#Current address: Clinical Brain Disorders Branch, NIMH, Bldg 10, 9000 Rockville Pike, Bethesda, MD 20892-1365 USA
NIH Public Access
Author Manuscript
J Agric Food Chem. Author manuscript; available in PMC 2011 April 14.
Published in final edited form as:
J Agric Food Chem. 2010 April 14; 58(7): 3996–4000. doi:10.1021/jf9029332.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
for dementia and represents the first clinical appearance of neurodegeneration for a substantial
subset of individuals who will progress to AD (5). There is no remedy for dementia, and it is
not clear when or if effective therapy will be developed. However, it has been proposed that
interventions initiated in individuals with pre-dementia conditions such as MCI might forestall
progression of cognitive decline, and MCI may represent the final point at which intervention
can be effective (6).
Dietary approaches hold promise as effective and safe preventive interventions. Dietary factors
represent the most potent determinants of metabolic health and have been shown to mitigate
specific mechanisms of neurodegeneration (7). Polyphenol consumption is important in this
regard, and epidemiological studies indicate that consumption of fruits and vegetables is
associated with lower risk of neurodegenerative disorders and better cognitive performance in
the elderly (8). Furthermore, there is pre-clinical evidence that blueberry supplementation
enhances memory and motor performance in aged animals (9–11). These effects have been
attributed in large part to anthocyanins, which enter the brain and other organs (11–13).
Enhanced signaling and neuroprotection have been observed in association with blueberry
supplementation (14–15). Following blueberry feeding, anthocyanins have been identified in
specific cerebral sites, including hippocampus and neocortex, regions essential for cognitive
function (12), and anthocyanin distribution in the hippocampus has been related to increased
neuronal signaling in that structure (11). Further, there are indications that anthocyanins have
insulin-like and glitazone-like properties that contribute to improved metabolic function (16–
17) and lipid lowering effects (18).
This body of pre-clinical findings involving several actions pertinent to neurodegeneration
suggests that blueberry consumption may be beneficial with respect to memory function in
older adults at risk for dementia. As an initial assessment of this hypothesis, we performed a
moderate-term trial involving daily supplementation with wild blueberry juice and assessed
changes in neurocognitive function.
Materials and Methods
The study protocol was approved by the University of Cincinnati Medical Institutional Review
Board, and each enrolled participant signed the informed consent document. Older adult men
and women were recruited from the Cincinnati region with print advertising in the form of
flyers posted at senior centers and advertisements placed in the Cincinnati Enquirer, the major
daily newspaper. The recruitment ads solicited participation of older adults with mild, acquired
memory decline for a dietary supplement study. We enrolled nine participants (5 men, 4
women) who had experienced age-related memory decline such as forgetfulness and
prospective memory lapses. The mean (± SD) age of the sample was 76.2 (± 5.2) years, and
the mean (± SD) educational level was 15.6 (± 1.5) years. Subject recruitment for this study
occurred as an extension of another, controlled berry juice trial evaluating effects of Concord
grape juice against a placebo beverage in the same population (19). The design of that study
with respect to the duration of the intervention, daily dosage, and the administration of pre-
and post-intervention assessments was identical to the blueberry juice trial, and it afforded the
opportunity to utilize data from its placebo group as a control. The placebo comparison sample
was recruited and screened in the same manner and consisted of seven subjects with early
memory decline. There was no statistical difference in age (80.2 ± 6.3 years) or educational
level (13.4 ± 3.1 years) between this group and the blueberry sample. The placebo beverage
was produced by Welch Foods, Inc., Concord, MA, USA. It contained no juice or natural
polyphenol and was matched to Concord grape juice with respect to overall carbohydrate
composition and caloric load (3.0 kJ/mL).
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Prospective participants were assessed with structured interview instruments to determine
eligibility for study inclusion. The Academic and Medical History Questionnaire (20) was used
to obtain demographic information and information regarding academic attainment, current
and past medical conditions, and medication and substance use. Those with diabetes, substance
abuse disorder, or diagnosed psychiatric or neurological condition were excluded as well as
those using medications that might affect outcome measures such as benzodiazepines. Level
of memory impairment was determined with the Clinical Dementia Rating (CDR), which elicits
information from the participant and an informant (typically, spouse or adult child) concerning
the nature and extent of cognitive decline as manifested in everyday activities at home and in
the community (21). The domains memory, orientation, problem solving, community affairs,
home activities, and personal care were evaluated, and the ratings for each domain contributed
to a global CDR classification with the memory domain weighted most heavily. CDR
classifications include no impairment, mild decline, and mild, moderate, and severe dementia.
We enrolled individuals with mild decline corresponding to Mild Cognitive Impairment and
excluded those with CDR classifications indicating no impairment and those with mild,
moderate, and severe dementia. In addition to the global CDR classification, the sum of boxes
score also was derived. This score represented the arithmetic sum of the category ratings across
the six domains of functioning and served as a means of quantifying the overall level of
functional decline (22).
Wild blueberry juice was commercially prepared from ripe, frozen wild (lowbush) blueberries
(Vaccinium angustifolium Aiton) by Van Dyk’s Health Juice Products Ltd (Caledonia, Nova
Scotia, Canada) and was provided for this research by the Wild Blueberry Association of North
America, Old Town, ME, USA. Berries were thawed, pressed, filtered, pasteurized, and then
bottled in one liter amber glass bottles. One kg of blueberry fruit produced approximately 735
mL of single-strength juice.
Analyses were performed on samples of the juice used in this study. The most abundant
dissolved components in the wild blueberry juice were glucose, fructose, and malic and citric
acid (23). Colorimetric measurement of total juice phenolics indicated a concentration of 2.38
g gallic acid equivalents/L (24). The major phenolics in the juice were the hydroxycinnamic
acid ester, chlorogenic acid at approximately 734 mg/L, and flavonoid anthocyanins at 877 mg
cyanidin 3-glucoside equivalents/L juice based on HPLC analysis as described elsewhere
(25). Losses in anthocyanins and other phenolics in blueberry juice can occur during storage.
During the approximately three month storage of the juice samples, losses in the total phenolics
and anthocyanins were determined to be 23% and 20%, respectively, for juice that was stored
under refrigeration in amber bottles.
Daily consumption was maintained between 6 mL/kg and 9 mL/kg by using a dosing schedule
determined by body weight. Individuals weighing 54 to 64 kg were prescribed 444 mL/day,
those weighing between 65 and 76 kg consumed 532 mL/day, and those weighing between 77
and 91 kg consumed 621 mL/day. Table 1 contains data on phenolic and anthocyanin intake
determined from samples of the blueberry juice used in this study. This dosage range
corresponded to the volume used in human trials with Concord grape juice (19,26). The study
participants were blind to the supplement they received and were told that the study product
might be grape juice, blueberry juice, or a berry placebo beverage. The juice was stored in a
cold room at 4 °C prior to distribution. The subjects were instructed to refrigerate the juice at
home and to take prescribed daily quantities in equal, divided dosages with the morning,
midday, and evening meals. We provided containers with individual dosages marked for each
subject to minimize risk of mis-measuring. The period of the intervention was 12 weeks.
Despite the fact that this represented a much smaller percentage of total lifespan for humans
than for rodents, we expected that the biological response would occur in substantially the same
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timeframe in view of the correspondence between previous human and animal studies.
Blueberry supplementation for similar timeframes in experiments with aged animals have
demonstrated cognitive performance improvements (12,14). In addition, human trials of this
duration with berry juice have shown beneficial changes in inflammatory markers and
antioxidant capacity (26).
The subjects were given bottled juice at the baseline visit and at an interim visit during week
6 of the intervention. Adherence to the consumption protocol and side effects were assessed
with weekly telephone contacts and by direct interview during the interim and final visits. The
subjects were instructed to avoid berry fruits and juices and berry extracts for the duration of
the trial and were provided a list of foods and supplements to avoid. This list included fruits
and beverages such as blueberries, blackberries, cherries, grapes, grape juice, pomegranates,
strawberries, and wine among others.
Assessments were performed at pre-treatment baseline and during the final week of the
intervention. The primary outcomes were measures of memory function, including the Verbal
Paired Associate Learning Test (V-PAL; 27) and the California Verbal Learning Test (CVLT;
28). Paired associate tasks have identified those with progressive neurodegeneration and
demonstrated sensitivity to early and more advanced Alzheimer’s disease (29), and the V-PAL
has been shown to be sensitive to developmental performance changes between young, middle-
aged, and elderly women (30). This task calls for the subject to learn new associations between
common one- and two-syllable semantically unrelated words (e.g., help-years). The V-PAL
performance score represents the cumulative number of correct responses summed across four
learning and testing trials. The CVLT is a widely-used list learning and recall task that has
demonstrated sensitivity to age-related memory changes, MCI, and dementia (31). It involves
a 16-item list of common words that can be grouped into semantic categories. However, there
is no demand to encode new associations. The free recall score was used to assess word list
retention. Both of these verbal memory tests were included because they induce somewhat
different cognitive demands. Whereas the V-PAL requires the formation of novel associations,
the CVLT involves acquisition and retention of a list of individual words. Both rely on
hippocampal processing, although the paired associate task may be more resource intensive
and potentially more sensitive to cognitive aging effects (32).
Alternate forms of each memory task were used at the baseline and final visits so that the
specific test item content was not repeated. The use of alternate forms substantially mitigates
practice effects associated with test-retest designs, in particular with respect to memory tests
(33). However, alternate forms may not eliminate performance gain at re-test related to
procedural practice effects; that is, familiarity with the test procedure (34).
Mood was assessed with the Geriatric Depression Scale (GDS; 35), a 30-item inventory
designed to evaluate symptoms of depression in older adults. We also measured weight and
waist circumference, and obtained fasting blood samples for determinations of serum glucose
and insulin values by the biochemistry laboratory of the General Clinical Research Center
(GCRC) at the University of Cincinnati.
The primary statistical analyses included dependent sample t-tests to determine change from
baseline to final visit in memory performance, mood, body anthropometrics, and metabolic
parameters. We set α probability of type 1 error at 0.05 to report statistically significant effects.
Given the preliminary nature of this trial, we reported trends at α 0.10. We also computed
Cohen’s d effect size statistics (36) for these analyses, which are characterized as small (0.2),
medium (0.5), and large (0.8).
Because of concern regarding performance gain with repeated memory testing, we also
performed analyses of covariance (ANCOVA) to control for potential procedural practice
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effects by comparing memory performances of the blueberry sample with that of the grape
placebo sample from the companion study. These analyses isolated the effect of the intervention
using outcome scores from the final visit as the dependent measure and the corresponding score
from the baseline visit as covariate measure (37). Cohen’s f (36) represents the effect size
statistic for these analyses, which are small (0.1), medium (0.25), and large (0.40).
Table 2 contains information concerning the sample characteristics. The mean age of our
sample and the mean Clinical Dementia Rating sum boxes score are consistent with other
studies of Mild Cognitive Impairment (22). The level of depressive symptoms as measured by
the Geriatric Depression Scale was within the non-depressed, normal range (35). The average
waist circumference was high (98 cm), with the mean (SD) waist circumference for the men
at 102.5 (5.0) cm and at 92.5 (15.1) cm for the women. These waist circumference values were,
respectively, near and just above gender-specific cutoffs established as markers of insulin
resistance and metabolic pathology (38). While baseline fasting glucose was within normal
limits for our GCRC laboratory standards (65 to 115 mg/dl), mean fasting insulin was in the
hyperinsulinemic range ( 15 μU/mL). As would be expected, waist circumference was
significantly correlated with fasting insulin, r = .72, p = 0.04.
Figure 1 shows changes in memory performance from pre-intervention baseline to the final
assessment. The V-PAL cumulative learning score was significantly improved at 12 weeks
(13.2 v 9.3), t(8) = 3.42, p = 0.009, effect size d = 1.78. With α = .05, power = 0.95. In addition,
word list recall performance on the CVLT improved significantly (9.6 v 7.2), t(8) = 2.34, p =
0.04, d = 1.18. Power for this effect was 0.65 at α = 0.05.
Weight (80.3 v 80.3 kg), t(8) = .05, p = 0.95, and waist circumference (98.0 v 98.9 cm), t(8) =
1.10, p = 0.30, did not change as a result of the intervention. There was a nonsignificant trend
indicating reduced depressive symptoms at 12 weeks relative to baseline (3.5 v 5.8), t(8) =
1.96, p = 0.08. There also was a trend toward lower fasting glucose for the blueberry group at
12 weeks compared with baseline (91.2 v 94.6 mg/dl), t(8) = 1.85, p = 0.10. The mean fasting
insulin level was reduced to within the normal range at 12 weeks (12.1 v 15.9 μU/mL), although
this reduction from baseline level was not statistically significant, t(8) = 1.21, p = 0.26.
Ancillary ANCOVA tests compared changes in memory performance for the blueberry sample
with that of the placebo beverage group from the companion study (19). Figure 2 shows that
the performance of the blueberry juice group exceeded that of the placebo beverage group,
with a significant effect for V-PAL performance (p = 0.03, Cohen’s effect size, f = 0.48),
although the effect for list recall was not maintained (p = 0.12, Cohen’s f = 0.32).
This study indicated that wild blueberry juice supplementation for 12 weeks improved memory
function in older adults with early memory decline. To our knowledge, this is the first human
trial assessing the potential benefit of blueberry supplementation on neurocognitive function
in older adults with increased risk for dementia. Although the sample size was relatively small,
effect sizes were moderate to large for both the primary and secondary analyses. The magnitude
of the effect for the paired associate task exceeded that for the list learning task and was
maintained in the ANCOVA analysis. While both paired associate and list learning tasks rely
on hippocampal mediation, the former engages integrated parahippocampal processing to
encode associations between unrelated terms (32). Accordingly, the greater magnitude of effect
for the V-PAL may reflect the greater resource demand and greater sensitivity of the paired
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associate task in these subjects with mild decline and, correspondingly, greater performance
enhancement in response to blueberry treatment.
We also observed trends suggesting diminished depressive symptoms and reduced fasting
glucose levels, measures which would not be expected to be susceptible to practice effects.
While the mean depression symptom score at the pre-intervention assessment was below
clinically significant levels (35), the reduction is notable and provides further corroboration of
neurocognitive benefit associated with the blueberry intervention. The trend toward lower
glucose levels along with correction of fasting insulin to the normal range is interesting and
suggests one possible mechanism of effect. While much of the preclinical research has focused
on antioxidant, anti-inflammatory, and neuronal signaling properties, there also are recent data
supporting the notion that anthocyanins can enhance glucose disposal through a number of
mechanisms (16,17). This factor also may contribute to improved neurocognitive function.
Improved glucose disposal and correction of hyperinsulinemia would be expected to be
associated with reduction of inflammation and greater clearance of central beta-amyloid as
well as enhanced signaling in memory centers (39). It will be of interest to pursue investigations
of blueberry supplementation on metabolic and other putative mechanisms of
neurodegeneration to determine whether changes in cognitive function can be associated with
metabolic enhancement and downstream mechanisms such as inflammation and
One of the primary limitations of this study was the small sample size. Although the significant
effects and substantial effect sizes are encouraging, there is a clear need for larger trials. The
absence of a fully matched control product also was a limitation. While data from the grape
juice placebo sample did provide adequate control on a number of dimensions, including
identical study design and duration of the intervention period, use of a product designed to
simulate characteristics of berry juice, daily dosage, and control for potential practice effects,
it was not matched to the blueberry juice for glycemic load. This raises the possibility that the
relatively greater glycemic content of the placebo beverage might have influenced cognitive
performance. While this concern is mitigated by the fact that change in metabolic function was
not observed in the companion study (27), use of a fully matched placebo product in future
studies will be essential.
These preliminary memory findings are encouraging and suggest that consistent
supplementation with blueberries may offer an approach to forestall or mitigate
neurodegeneration. Interpretation of our findings should be tempered because of the relatively
small sample size and the absence of a blueberry-specific control, although comparison with
the analogous placebo beverage data provides some assurance that the observed changes in
memory performance were not attributable to practice effects. Replication of the findings in a
larger, controlled trial will be important to corroborate and amplify these data. On balance, this
initial study establishes a basis for further human research of blueberry supplementation as a
preventive intervention with respect to cognitive aging.
Material and funding support provided by the Wild Blueberry Association of North America and NIH grant #
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Figure 1.
Memory performances for the blueberry juice sample at the 12-week final visit relative to pre-
intervention baseline as measured by the Verbal Paired Associate Learning Test (V-PAL) and
the California Verbal Learning Test (CVLT) free recall task. Data show significantly improved
performances for both the V-PAL, p = 0.009, and CVLT recall, p = 0.04.
KRIKORIAN et al. Page 9
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Figure 2.
Post-intervention final visit mean values comparing memory performance for subjects (n = 7)
who consumed placebo beverage and subjects who consumed wild blueberry juice (n=9) for
12 weeks. The ANCOVA analyses indicated significantly improved paired associate learning
(V-PAL) performance, F(1,13) = 5.58, p = 0.03, although improved recall on the CVLT for
the blueberry juice subjects did not achieve statistical significance, F(1,13) = 2.27, p = 0.12.
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KRIKORIAN et al. Page 11
Table 1
Daily Blueberry Juice Intake by Weight, Total Phenolics, and Anthocyanins.
Body weight, kg Blueberry juice intake, mL/d Phenolics, g gallic acid eq. Anthocyanins, g cyanidin 3-glucoside eq.
54–64 444 1.056 0.428
65–76 532 1.266 0.512
77–91 621 1.478 0.598
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KRIKORIAN et al. Page 12
Table 2
Subject Sample Characteristics
Age, years 76.2 (5.2)
Education, years 15.6 (1.5)
CDRa sum boxes score .88 (.48)
GDSb score 5.8 (6.2)
Weight, kg 80.3 (12.0)
Waist, cm 98.0 (11.2)
Fasting glucose, mg/dl 94.6 (10.1)
Fasting insulin, μU/mL 15.9 (14.1)
aNote. CDR = Clinical Dementia Rating.
bGDS = Geriatric Depression Scale.
J Agric Food Chem. Author manuscript; available in PMC 2011 April 14.
... For example, one study found that chronic treatment with resveratrol improved cognitive function in aged rats [173] but not in young mice [174]. Similarly, a study on the effects of blueberry extract on cognitive function found that supplementation improved memory in aged mice [175] but had no effect on young mice. In terms of strain differences, a study comparing the effects of green tea extract on cognitive function in two different strains of mice found that the extract improved memory in SAMP8 but not in the SAMR1 [176]. ...
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Emerging evidence suggests that cognitive impairments may result from various factors, such as neuroinflammation, oxidative stress, mitochondrial damage, impaired neurogenesis, synaptic plasticity, blood–brain barrier (BBB) disruption, amyloid β protein (Aβ) deposition, and gut dysbiosis. Meanwhile, dietary polyphenol intake in a recommended dosage has been suggested to reverse cognitive dysfunction via various pathways. However, excessive intake of polyphenols could trigger unwanted adverse effects. Thus, this review aims to outline possible causes of cognitive impairments and how polyphenols alleviate memory loss via various pathways based on in vivo experimental studies. Thus, to identify potentially relevant articles, the keywords (1) nutritional polyphenol intervention NOT medicine AND neuron growth OR (2) dietary polyphenol AND neurogenesis AND memory impairment OR (3) polyphenol AND neuron regeneration AND memory deterioration (Boolean operators) were used in the Nature, PubMed, Scopus, and Wiley online libraries. Based on the inclusion and exclusion criteria, 36 research papers were selected to be further reviewed. The outcome of all the studies included supports the statement of appropriate dosage by taking into consideration gender differences, underlying conditions, lifestyle, and causative factors for cognitive decline, which will significantly boost memory power. Therefore, this review recapitulates the possible causes of cognitive decline, the mechanism of polyphenols involving various signaling pathways in modulating the memory, gut dysbiosis, endogenous antioxidants, bioavailability, dosage, and safety efficacy of polyphenols. Hence, this review is expected to provide a basic understanding of therapeutic development for cognitive impairments in the future.
... Studies on the neuroprotective abilities of anthocyanins in humans are scarce. In a small cohort of older adults with early memory impairment, wild blueberry juice consumption daily for 12 weeks improved pairwise-associated learning and wordlist recall (Krikorian et al. 2010b). In the Nurses' Health Study, high consumption of blueberries and strawberries was also associated with a delay in cognitive ageing of approximately 2.5 years (Devore et al. 2012). ...
The gradual ageing of the world population has been accompanied by a dramatic increase in the prevalence of obesity and metabolic diseases, especially type 2 diabetes. The adipose tissue dysfunction associated with ageing and obesity shares many common physiological features, including increased oxidative stress and inflammation. Understanding the mechanisms responsible for adipose tissue dysfunction in obesity may help elucidate the processes that contribute to the metabolic disturbances that occur with ageing. This, in turn, may help identify therapeutic targets for the treatment of obesity and age-related metabolic disorders. Because oxidative stress plays a critical role in these pathological processes, antioxidant dietary interventions could be of therapeutic value for the prevention and/or treatment of age-related diseases and obesity and their complications. In this chapter, we review the molecular and cellular mechanisms by which obesity predisposes individuals to accelerated ageing. Additionally, we critically review the potential of antioxidant dietary interventions to counteract obesity and ageing.KeywordsAgeingObesityMetabolic syndromeOxidative stressInflammationNutraceuticalsDietary interventions
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Epidemiological studies have shown associations between polyphenol-rich fruit intake and bone health, and preclinical studies have shown that blueberries improve bone health. To determine the genotype and dose of blueberries that are effective in ameliorating age-related bone loss, a multi-institutional team of investigators performed in vitro, preclinical, and clinical studies on blueberry varieties that differed in flavonoid profiles. Principal component analysis was used to select blueberry genotypes that varied in anthocyanin profiles. Total phenolic content did not predict the bioavailability of polyphenolic compounds in rats. A range in bioavailability was observed in individual polyphenolic compounds across genotypes. Both alpha and beta diversity analyses indicated that gut microbiome profiles varied with blueberry dose in rats. Additionally, the identification of specific taxa, such as Prevotellaceae_UCG-001 and Coriobacteriales, increasing after blueberry consumption adds to the mounting evidence of their role in polyphenol metabolism. All of the sources of variation can inform blueberry breeding practices to influence precision nutrition.
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Alzheimer’s disease (AD) is the most common cause of dementia, and its prevalence rises with age. Inflammation and altered antioxidant systems play essential roles in the genesis of neurodegenerative diseases. In this work, we looked at the effects of MemophenolTM, a compound rich in polyphenols derived from French grape (Vitis vinifera L.) and wild North American blueberry (Vaccinium angustifolium A.) extracts, in a rat model of AD. Methods: For 60 days, the animals were administered with AlCl3 (100 mg/kg, orally) and D-galactose (60 mg/kg, intraperitoneally), while from day 30, MemophenolTM (15 mg/kg) was supplied orally for 30 consecutive days. AlCl3 accumulates mainly in the hippocampus, the main part of the brain involved in memory and learning. Behavioral tests were performed the day before the sacrifice when brains were collected for analysis. Results: MemophenolTM decreased behavioral alterations and hippocampus neuronal degeneration. It also lowered phosphorylated Tau (p-Tau) levels, amyloid precursor protein (APP) overexpression, and β-amyloid (Aβ) buildup. Furthermore, MemophenolTM reduced the pro-oxidative and pro-inflammatory hippocampus changes caused by AD. Our finding, relevant to AD pathogenesis and therapeutics, suggests that MemophenolTM, by modulating oxidative and inflammatory pathways and by regulating cellular brain stress response mechanisms, protects against the behavioral and histopathological changes associated with AD.
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This perspective paper is a product of a workshop of experts convened by Institute for the Advancement of Food and Nutrition Sciences (IAFNS), a non-profit organization that brings together scientists from government, academia, and industry to catalyze science relevant to food and nutrition. An expert group was convened in March 2022 to discuss the current issues surrounding cognitive task selection in nutrition research, with a focus on solutions towards informing dietary guidance for cognitive health, to address a gap identified in the 2020 US DGAC report, specifically the "considerable variation in testing methods used, [and] inconsistent validity and reliability of cognitive testing methods" (p.31). To address this issue, we firstly undertook an umbrella review of relevant reviews already undertaken; these indicate agreement on some of the issues that affect heterogeneity in task selection, and on many of the fundamental principles underlying selection of cognitive outcome measures. However, resolving the points of disagreement is critical to ensuring meaningful impact on the issue of heterogeneity in task selection; these issues hamper evaluation of existing data for informing dietary guidance. This summary of the literature is therefore followed by the expert group's perspective in the form of a discussion of potential solutions to these challenges, with the aim of building on the work of previous reviews in the area and advancing dietary guidance for cognitive health. STATEMENT OF SIGNIFICANCE: Despite several high-quality reviews in this field over the last two decades, there has been little in the way of substantive change in the methods being used to conduct studies, hampering harmonization of the evidence and thus, its utility for informing dietary guidance. The present paper comprehensively updates the field by firstly providing an umbrella review of the published reviews, followed by the IAFNS expert group's perspective on how to move the field forward by addressing the challenges and areas of disagreement in the existing reviews. REGISTERED ON PROSPERO: CRD42022348106. Data described in the manuscript, code book, and analytic code will be made publicly and freely available without restriction at
Background: Evidence suggests that intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. Methods: A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome and blood parameters were measured at baseline and 12 weeks following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using micro-elution solid phase-extraction coupled with LC-MS. Results: A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared to placebo (0.86%; 95% CI 0.56, 1.17, p<0.001; -3.59 mmHg; 95% CI -6.95, -0.23, p=0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task were also found following WBB treatment compared to placebo (p<0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared to placebo. No changes in CBF or gut microbiota composition were found. Conclusions: Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function, and decreases 24h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future cardiovascular disease (CVD) disease risk in an older population, and may improve episodic memory processes and executive functioning in older adults at risk of cognitive decline. CLINICAL TRIAL REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT04084457.
The purpose of this study was to analyze the axonal regeneration and therapeutic effects of curcumin and blueberry administration following peripheral nerve injury using stereological, electron microscopic and electrophysiological methods. Animals in were assigned into one of four groups - control (Cont), injury (Inj), injury+curcumin (Cur) and injury+blueberry (Blue). Following the induction of sciatic nerve crush injury (75 Newtons for 5sec) in the Inj, Cur, and Blue groups, the rats in the Cur group received intraperitoneal injection of 30mg/kg curcumin (Sigma C1386) and the rats in the Blue group received 4g/kg blueberry by gavage over a four-week period. The rats in the Cont and Inj groups were not exposed to any substance. All animals were given standard chow. Sciatic functional index analyses were performed on the 14th and 28th days after injury, and electromyography (EMG) results were recorded. Stereological analysis of the nerve was performed under light microscopy. Light and electron microscopies were used for the histopathological evaluation of the sciatic nerve. Analysis of myelinated axon numbers revealed no significant differences between the Inj group and the Cur and Blue groups. However, a significant difference was observed between the Blue and Inj groups in terms of axonal areas. EMG test results differed between the Blue and the Inj groups (p<0.05), but no significant difference was observed between the Inj and Cur groups. Electron microscopic analysis revealed protective effects of curcumin and blueberry treatment after injury. The use of the curcumin and blueberry may represent a supportive approach to the protection of nerve fibers after peripheral nerve crush injury.
Mild cognitive impairment (MCI) and dementia are associated with lifestyle risk factors, making lifestyle medicine a potentially viable intervention for people with MCI and dementia. The present study aims to examine the effectiveness of lifestyle medicine on cognitive functions among people with MCI and dementia, by performing a systematic review and meta-analysis on randomized controlled trials (RCT). A systematic literature search was conducted to extract RCTs adopting lifestyle interventions of diet, exercise, and stress management or emotional well-being. Results showed that 65 studies were eligible. Exercise was the most promising lifestyle intervention that improved various cognitive functions among people with MCI and dementia, and was more effective in MCI than in dementia. Interventions on stress management or emotional well-being did not show a significant effect on people with MCI, and the evidence for people with dementia was insufficient to conclude. Similarly, due to the lack of RCTs on a healthy dietary pattern, the effectiveness of diet interventions was not examined. In conclusion, the exercise component of lifestyle medicine can be an effective and clinically significant intervention for protecting people with MCI and dementia against cognitive declines, especially when served as an early intervention at the stage of MCI.
Neurodegenerative diseases are among the most prevalent age‐related diseases in humans with increasing incidence and no cure. In the past years, research on (poly)phenols focused on flavonoids has been tackling the missing links of (poly)phenol potential for the prevention and treatment of neurodegenerative diseases. (Poly)phenols from dietary sources have been emerging as potential targets to modulate the progression and development of such multifactorial diseases through diet. The most abundant circulating metabolites of dietary (poly)phenols, the low molecular weight (poly)phenol metabolites resulting from phase I and II metabolism and microbiota transformations have been listed. These metabolites are known to reach human circulation. However, their brain permeability and role in neuroinflammation are two topics that still have research gaps, therefore hampering a comprehensive view of their impact to mitigate brain inflammation through the blood‐brain barrier and the underlying mechanisms.
Wine differs from other alcoholic beverages due to the abundance of the presence of various groups of phenolic compounds. Phenolics are of high technological importance since they can directly affect the sensory and health-promoting properties of wines. This chapter is divided into four sections. In the first section, the phenolic composition of grapes is described along with their extraction during the various stages of wine production: processing of raw material, alcoholic fermentation, stabilization, aging, bottling, and storage. The second section focuses on the utilization of the wineries' by-products for the production of innovative and functional foods. Section three is dedicated to the description of the simple analytical methods, mainly those that are based on chromatography and spectroscopy, that can be applied to determine the phenolic composition and the antioxidant activity of the wine. Finally, in section four, the health benefits associated with the consumption of wine phenolic compounds are discussed.
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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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Emerging evidence from our lab indicate that fruits and vegetables, in particular blueberry (BB) extracts, are able to ameliorate age-related declines in neuronal and cognitive function, common in disorders such as Alzheimer disease. The current study examined if the beneficial effects were also discernable with supplementation of BB extracts, in an already well balanced diet. Indeed, following an 8 week supplementation regime, age-related declines in several behavioral parameters such as balance, coordination, working memory and reference memory were still protected against. Similarly, BB extracts also potentiated oxotremorine enhancement of K+-evoked release of dopamine from striatal slices. Decline in the dopaminergic system have been shown to have a profound effect on cognitive functions. The improvement in dopamine release may have been due in part to the observed increase in striatal vitamin C levels. Although assessment of serum transaminase levels in BB supplemented animals appeared to suggest improved liver function, this was not thought to be the reason for the elevated vitamin C levels. The underlying mechanism for this is unclear. Together these findings highlight the diverse in vivo actions of dietary polyphenolics, a number of which may be important against age-related declines in certain brain functions. Furthermore they are to be able to mediate protective effects despite the diet containing sufficient concentrations of antioxidants.
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.