James A Joseph’s research while affiliated with United States Department of Agriculture and other places

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Publications (186)


Participant Flowchart. Chart showing the progress through the phases of a 90-day randomized, double-blind, placebo-controlled study evaluating the effect of 24 g/day dietary blueberry in healthy older adults
Task-Switching Test. a Screen capture of task display, b No significant group differences were observed in reaction times to correct responses, and c A significant diet-group-by-study-visit interaction (F (2, 70) = 3.587, p = 0.033, ηp² = 0.09) revealed that participants who consumed blueberry made fewer errors for each stimulus condition across study visits relative to placebo controls; all error bars denote SEM
California Verbal Learning Test. A significant intervention group by study visit interaction (F (1, 35) = 5.024, p = 0.031, ηp² = 0.126) revealed that participants who consumed blueberry decreased and placebo controls increased the number of repetition errors committed when tested after 90 days of dietary intervention; all error bars denote SEM
Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial
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  • Publisher preview available

April 2018

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704 Reads

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159 Citations

European Journal of Nutrition

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James A. Joseph

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PurposeAs populations shift to include a larger proportion of older adults, the necessity of research targeting older populations is becoming increasingly apparent. Dietary interventions with blueberry have been associated with positive outcomes in cell and rodent models of aging. We hypothesized that dietary blueberry would improve mobility and cognition among older adults. Methods In this study, 13 men and 24 women, between the ages of 60 and 75 years, were recruited into a randomized, double-blind, placebo-controlled trial in which they consumed either freeze-dried blueberry (24 g/day, equivalent to 1 cup of fresh blueberries) or a blueberry placebo for 90 days. Participants completed a battery of balance, gait, and cognitive tests at baseline and again at 45 and 90 days of intervention. ResultsSignificant supplement group by study visit interactions were observed on tests of executive function. Participants in the blueberry group showed significantly fewer repetition errors in the California Verbal Learning test (p = 0.031, ηp2 = 0.126) and reduced switch cost on a task-switching test (p = 0.033, ηp2 = 0.09) across study visits, relative to controls. However, no improvement in gait or balance was observed. Conclusions These findings show that the addition of easily achievable quantities of blueberry to the diets of older adults can improve some aspects of cognition.

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The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing

September 2015

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657 Reads

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106 Citations

The British journal of nutrition

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James A. Joseph

Previously, it has been shown that strawberry (SB) or blueberry (BB) supplementations, when fed to rats from 19 to 21 months of age, reverse age-related decrements in motor and cognitive performance. We have postulated that these effects may be the result of a number of positive benefits of the berry polyphenols, including decreased stress signalling, increased neurogenesis, and increased signals involved in learning and memory. Thus, the present study was carried out to examine these mechanisms in aged animals by administering a control, 2 % SB- or 2 % BB-supplemented diet to aged Fischer 344 rats for 8 weeks to ascertain their effectiveness in reversing age-related deficits in behavioural and neuronal function. The results showed that rats consuming the berry diets exhibited enhanced motor performance and improved cognition, specifically working memory. In addition, the rats supplemented with BB and SB diets showed increased hippocampal neurogenesis and expression of insulin-like growth factor 1, although the improvements in working memory performance could not solely be explained by these increases. The diverse polyphenolics in these berry fruits may have additional mechanisms of action that could account for their relative differences in efficacy.


Method improve spatial memory via pterostilbene administration

May 2015

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15 Reads

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1 Citation

Disclosed is a pharmaceutical composition for treating oxidative stress comprising a therapeutically effective amount of a substantially pure compound of pterostilbene and a physiologically acceptable carrier. Pterostilbene is administered in an amount between about 2.5 mg to about 10 mg per kilogram of subject body weight. Also disclosed is a method for increasing a working memory of a subject, the method comprising administrating an effective amount of a substantially pure compound of pterostilbene, wherein the working memory for a subject increase and the therapeutic effectiveness is about 10 mg of pterostilbene per kilogram of subject body weight.


Method to ameliorate oxidative stress and improve working memory via pterostilbene administration

August 2014

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17 Reads

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3 Citations

Disclosed is a pharmaceutical composition for treating oxidative stress comprising a therapeutically effective amount of a substantially pure compound of pterostilbene and a physiologically acceptable carrier. Pterostilbene is administered in an amount between about 2.5 mg to about 10 mg per kilogram of subject body weight. Also disclosed is a method for increasing a working memory of a subject, the method comprising administrating an effective amount of a substantially pure compound of pterostilbene, wherein the working memory for a subject increase and the therapeutic effectiveness is about 10 mg of pterostilbene per kilogram of subject body weight.



Nutrients and Food Constituents in Cognitive Decline and Neurodegenerative Disease

December 2013

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152 Reads

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1 Citation

The greatest health problem facing society, developing as well as developed, is the increasing prevalence of age related chronic disease resulting from greater survival of the oldest elderly members. While the medical community is searching for magic pills that cure, current evidence instead demonstrates that nutritional and other lifestyle modification is at the core essential to reducing the prevalence of chronic diseases. Here we review current knowledge of molecular mechanisms responsible for nutritional benefits of food rich in polyphenols and polyunsaturated fatty acids. These findings offer a basis for improved health and reduced health costs.


Fig. 1 Latency to fall (mean ± SEM, seconds) in the rotarod test for the control and coffee groups. Means with different letters are significantly different from each other (p<0.05; Fisher's LSD)
Fig. 2 Morris water maze performance assessed as latency in seconds ( a ; mean ± SEM) and distance in meters ( b ) to find the hidden platform on days 3 and 4 of testing animals in the control and coffee groups. The asterisks indicate a difference (i.e., an improvement) between Trial 1 and Trial 2 performances ( one asterisk indicates p <0.05, two asterisks p <0.01), indicating improved working memory. Number sign indicates p <0.05, compared to control 
Fig. 3 Latency to fall (mean ± SEM, seconds) in the inclined screen test for the control, coffee, and caffeine groups. Means with different letters are significantly different from each other ( p <0.05; Fisher ’ s LSD) 
Fig. 4 Morris water maze performance assessed as latency in seconds ( a ; mean ± SEM) and distance in meters ( b ) to find the hidden platform on days 3 and 4 of testing animals in the control, coffee, and caffeine groups. The asterisks indicate a difference (i.e., an improvement) between Trial 1 and Trial 2 performances ( one asterisk indicates p <0.05, two asterisks p < 0.01), indicating improved working memory. Commercial at indicates p <0.05 compared to the ten-cup group 
Coffee, but not caffeine, has positive effects on cognition and psychomotor behavior in aging

January 2013

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872 Reads

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60 Citations

Journal of the American Aging Association

The complex mixture of phytochemicals in fruits and vegetables provides protective health benefits, mainly through additive and/or synergistic effects. The presence of several bioactive compounds, such as polyphenols and caffeine, implicates coffee as a potential nutritional therapeutic in aging. Moderate (three to five cups a day) coffee consumption in humans is associated with a significant decrease in the risk of developing certain chronic diseases. However, the ability of coffee supplementation to improve cognitive function in aged individuals and the effect of the individual components in coffee, such as caffeine, have not been fully evaluated. We fed aged rats (19 months) one of five coffee-supplemented diets (0, 0.165, 0.275, 0.55, and 0.825 % of the diet) for 8 weeks prior to motor and cognitive behavior assessment. Aged rats supplemented with a 0.55 % coffee diet, equivalent to ten cups of coffee, performed better in psychomotor testing (rotarod) and in a working memory task (Morris water maze) compared to aged rats fed a control diet. A diet with 0.55 % coffee appeared to be optimal. The 0.165 % coffee-supplemented group (three cups) showed some improvement in reference memory performance in the Morris water maze. In a subsequent study, the effects of caffeine alone did not account for the performance improvements, showing that the neuroprotective benefits of coffee are not due to caffeine alone, but rather to other bioactive compounds in coffee. Therefore, coffee, in achievable amounts, may reduce both motor and cognitive deficits in aging.


The ability of Walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells

December 2012

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120 Reads

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58 Citations

Nutritional Neuroscience

Unlabelled: Previous research from our lab has demonstrated that dietary walnut supplementation protects against age-related cognitive declines in rats; however, the cellular mechanisms by which walnuts and polyunsaturated fatty acids (PUFAs) may affect neuronal health and functioning in aging are undetermined. Objectives: We assessed if pretreatment of primary hippocampal neurons with walnut extract or PUFAs would protect cells against dopamine- and lipopolysaccharide-mediated cell death and calcium dysregulation. Methods: Rat primary hippocampal neurons were pretreated with varying concentrations of walnut extract, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, or docosahexaenoic acid prior to exposure to either dopamine or lipopolysaccharide. Viability was assessed using the Live/Dead Cellular Viability/Cytotoxicity Kit. Also, the ability of the cells to return to baseline calcium levels after depolarization was measured with fluorescent imaging. Results: Results indicated that walnut extract, alpha-linolenic acid, and docosahexaenoic acid provided significant protection against cell death and calcium dysregulation; the effects were pretreatment concentration dependent and stressor dependent. Linoleic acid and eicosapentaenoic acid were not as effective at protecting hippocampal cells from these insults. Discussion: Walnut extract and omega-3 fatty acids may protect against age-related cellular dysfunction, but not all PUFAs are equivalent in their beneficial effects.


Fig. (1). Gene expression values (means) for control-fed non-irradiated (0 Gy) rats, and 2.5 Gy irradiated rats fed the control, blueberry (BB), and strawberry (SB) diets.  
Changes in Gene Expression in the Rat Hippocampus Following Exposure to 56Fe Particles and Protection by Berry Diets

October 2012

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138 Reads

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28 Citations

Central Nervous System Agents in Medicinal Chemistry

Exposing young rats to particles of high energy and charge, such as 56Fe, enhances indices of oxidative stress and inflammation and disrupts behavior, including spatial learning and memory. In the present study, we examined whether gene expression in the hippocampus, an area of the brain important in memory, is affected by exposure to 1.5 Gy or 2.5 Gy of 1 GeV/n high-energy 56Fe particles 36 hours after irradiation. We also determined if 8 weeks of pre-feeding with 2% blueberry or 2% strawberry antioxidant diets could ameliorate irradiation-induced changes in gene expression. Alterations in gene expression profile were analyzed by pathway-focused microarrays for inflammatory cytokines and genes involved in nuclear factor-kappa B (NF-κB) signal transduction pathways. We found that genes that are directly or indirectly involved in the regulation of growth and differentiation of neurons were changed following irradiation. Genes that regulate apoptosis were up-regulated whereas genes that modulate cellular proliferation were down-regulated. The brains of animals supplemented with berry diets demonstrated an up-regulation of some protective stress signal genes. Therefore, these data suggest that 56Fe particle irradiation causes changes in gene expression in rats that are ameliorated by berry fruit diets.



Citations (85)


... The age range for participants (60-75 years) was selected because older adults showed measurable age-related motor and cognitive decline at these ages relative to young adults (20) . Inclusion criteria included BMI between 18·5 and 29·9 kg/m 2 , ability to walk 20 min unassisted, English fluency, self-reported adequate visual acuity and >12 months postmenopausal. ...

Reference:

Dietary strawberry improves cognition in a randomized, double-blind, placebo-controlled trial in older adults
Mobility and cognition: End points for dietary interventions in aging
  • Citing Article
  • January 2014

Nutrition and Aging

... Previous studies have found synergistic interaction among nutrients within berries and suggested that consumption of the whole berry fruit may result in even better protective effects against age-related cognitive decline compared to specific nutrients [67,88]. Several animal studies have shown that berry supplementation can reverse age-related cognitive impairment [69][70][71], alleviate cognitive decline induced by a high-fat diet, and promote a healthy gut microbiome, which was associated with reduced β-amyloid pathology in the mouse brain [72]. Some human intervention studies have also reported that cognitive function can be improved after berry supplementation [69,[73][74][75]. ...

Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial

European Journal of Nutrition

... Polyphenols are naturally occurring molecules in plants and fruits that have been studied extensively for their potential therapeutic benefit in a number of diseases, including mild cognitive impairment [16,17] and various neurodegenerative disorders [18][19][20]. Our group and others have shown that polyphenols can alleviate neurotoxicity in preclinical models of PD, including flavonoids (a subclass of polyphenols) such as green tea polyphenols [21][22][23], anthocyanins (ANC) [24][25][26][27], and isoflavones [28][29][30], as well as the phenolic acid derivative curcumin [31] and stilbenes such as resveratrol and oxyresveratrol [24,32]. ...

NUTRITIONAL INTERVENTION IN BRAIN AGING: Reducing the effects of inflammation and oxidative stress

Sub-cellular Biochemistry

... 26,27 Recent patent suggests that pterostilbene is effectively improvise working memory and reversing memory deficit. 28 The isosteric replacement of ethenyl carbon of stilbene with nitrogen shows cation-p stacking inter-action with the AChE Trp-84 at anionic subsite. 29 This imine also incorporates the required features for metal chelation and antioxidant activities as stated in the literature. ...

Method improve spatial memory via pterostilbene administration

... Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene; PTS) is a naturally derived antioxidant and antiinflammatory agent (Drolet et al. 2009;Vauzour 2012). Several studies have demonstrated pleiotropic pharmacological activities of PTS including anti-inflammatory, antioxidant, anticancer, analgesic and including inhibition of histone deacetylase-1 (HDAC1) (Joseph et al. 2008;Remsberg et al. 2008;Bhaskaran and Vishwaraman 2009;Acharya and Ghaskadbi 2013). Pertaining to antidiabetic activity, P. marsupium extract and PTS alone have demonstrated ability to lower blood glucose levels (Manickam et al. 1997;Grover et al. 2005). ...

Method to ameliorate oxidative stress and improve working memory via pterostilbene administration

... years old (mean, 7.6 years) at the beginning of delayed response testing, 21 female and 13 male, and 71 were "aged", 19.9-32.5 years old (mean, 25.0 years), 41 female and 30 male. Although our primary analyses treat age as a binary "young" vs "aged" variable (Coleman et al., 2004), we note that the age range spanned the entire adult lifespan of rhesus monkeys, albeit with the omission of middle-aged animals (14-19 years). ...

The need for multiple time points in aging studies (Reprinted by Neurobiology of Aging, vol 11, pp 1-2, 1989
  • Citing Article
  • January 2004

Neurobiology of Aging

... A study by Shukitt-Hale et al. (2006) demonstrated that rats fed a diet rich in anthocyanins from blueberries showed significant improvements in cognitive function, including enhanced memory and learning abilities. These effects were linked to a reduction in oxidative damage to neurons and an improvement in synaptic plasticity, which is crucial for learning and memory. ...

The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing

The British journal of nutrition

... Recently, dietary supplements possessing high antioxidant activity have received special attention in age-related memory decline [19,20]. In the current study, having two preventive targeted approaches, piperine injected peripherally into STZ-induced AD rats and three behavioral findings are of interest. ...

Fruit Polyphenolics and Brain Aging
  • Citing Article
  • January 2006

... Most radiation studies have examined males while a limited number of radiation studies have involved only female animals (Acevedo et al., 2008;Dayger et al., 2011;Rabin et al., 2013) or both male and female animals (Villasana et al., 2008(Villasana et al., , 2010bRabin et al., 2010;Haley et al., 2012;Liu et al., 2017Liu et al., , 2019Kronenberg et al., 2018;Krukowski et al., 2018;Hinkle et al., 2019). In comparing the direction of sex-differences in relative susceptibility to develop radiation-induced cognitive injury, the pattern might depend on the radiation exposure. ...

Cognitive differences between male and female rats following exposure to 56Fe particles

... In the central nervous system (CNS), radiation exposure significantly affects the hippocampus [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18], a structure critical for memory function. For example, object recognition memory [19], which uses a 24 h interval between learning and memory assessment to test hippocampal function [20] , is sensitive to effects of irradiation [21]. Object recognition memory is impaired in 2-month-old mice two weeks following 56 Fe ion irradiation [22] and twelve weeks following irradiation with protons [23]. ...

Effects of exposure to heavy particles and aging on object recognition memory in rats