Nutritional Properties of Walnuts and their effects on Brain Health

ZAKIR HUSSAIN

17-Arid-6249

INSTITUTE OF FOOD AND NUTRITIONAL SCIENCES

PIR MEHR ALI SHAH

ARID AGRICULTURE UNIVERSITY RAWALPINDI

ABSTRACT

English walnuts are rich in α-linolenic acid (ALA; 18:3n23) and linoleic acid (LA;

18:2n26) just as different polyphenolics, phytosterols, and micronutrients. Feeding studies

from our research facility have appeared dietary supplementation with walnuts can

enhance memory, cognizance, and engine work in matured creatures. The vast majority of

these examines have connected walnuts impacts to their high PUFA content, walnuts

notable polyphenol content assumes an essential job in decreasing the aggravation and

oxidative worry in the maturing mind. This survey tends to contemporary investigation

into the impacts of dietary walnuts on comprehension, engine work, and cerebrum

wellbeing. Although there exists an urgent need to develop effective treatments for age-

related cognitive decline and neurodegenerative disease, prevention strategies have been

underdeveloped. Primary prevention in many of these neurodegenerative diseases could

be achieved earlier in life by consuming a healthy diet, rich in antioxidant and anti-

inflammatory phytochemicals, which offers one of the most effective and least expensive

ways to address the crisis. Evidence for the beneficial effects of consuming a walnut-rich

diet on cognitive health is reviewed in this article.

Keywords: walnut, Omega 3, brain health, neurodegenerative, diseases, memory.

INTRODUCTION
 Growing populations and increase in the mean life spans are leading to large aging

population in many countries. As a result of this demographic shift the incidence of

neurodegenerative diseases has increased. Dementia is the most prevalent

neurodegenerative disease as <35.6 million people are living with it (Thies W and Bleiler L,

2011). Neurodegenerative diseases have associations with chronic exposure to

inflammation and oxidative stress, accumulation of toxic proteins and the loss of protective

signaling. Interneuronal communications are modified by individual cell damage, causing

deficits in memory cognition and motor function. The result of this regular modifications

leads to the pathogenesis of neurodegenerative diseases i.e. dementia, Alzheimer disease,

Parkinson's disease, prion disease, Huntington disease and amyotrophic lateral sclerosis

(Marx J., 2006; Floyd RA and Hensley K., 2002).

The vulnerable part is central nervous system, inflammationand oxidative stress

mutually cause perpetuating effects that also affect other organ systems, Therefore,

including risk of developing other diseases such as diabetes, arthritis, cancer, heart disease.

These related pathologies and the direct effect of inflammation and direct stress on brain is

protected by systemic protection. Dietary intercessions might almost certainly avoid or

thwart neurodegeneration. Epidemiologic examination of the Mediterranean diet, which

comprises of high measures of organic products, vegetables, oats and insignificant

measures of liquor, red meat, and dairy items uncovered generous decreases in the danger

of AD in a substantial network based, case-control accomplice consider in 194 promotion

patients and 1790 non-AD patients (Morris MC et al., 2002). A couple of different
examinations likewise showed the advantages of the Mediterranean eating regimen in

lessening the danger of dementia, just as mortality, in AD patients, showing the essential

job of foods grown from the ground bioactive mixes on intellectual wellbeing (Scarmeas N

et al., 2006; Nooyens ACJ et al., 2011).

Walnut

English walnuts (Juglansregia L.) are rich in α-linolenic acid (ALA; 18:3n23) and

linoleic acid (LA; 18:2n26) just as different polyphenolics, phytosterols, and

micronutrients. Feeding studies from our research facility have appeared dietary

supplementation with walnuts can enhance memory, cognizance, and engine work in

matured creatures (Willis LM et al., 2009; Shukitt-Hale B et al., 2008). The vast majority of

these examines have connected walnuts impacts to their high PUFA content, walnuts

notable polyphenol content assumes an essential job in decreasing the aggravation and

oxidative worry in the maturing mind. This survey tends to contemporary investigation

into the impacts of dietary walnuts on comprehension, engine work, and cerebrum

wellbeing.

Walnut is exceedingly wealthy as far as monounsaturated greasy acids. Walnut is an

ideal wellspring of Omega 3 (which is fundamental unsaturated fat) and a wellspring of

Arachidonic acid. Walnut has been the image of being edified since bygone eras. The

natural structure of walnut is contrasted and the human mind, so it is considered as the

mind supplement. Walnut is the rich wellspring of numerous phyto-

concoction substances (Sen SM, 2013). These substances which have cancer prevention

agent impacts are the mixes of melatonin, ellagic acid, nutrient E, carotenoids and

polyphenols. These mixes have potential wellbeing impacts against maturing, diseases,

irritations and neurologic sicknesses (Sen SM, 2011) (Figure.1).

Figure 1. Chemical structure of walnut

As a Vitamin

Walnut is an ideal wellspring of vitamin E. Vitamin E in walnut fat has two

structures: alpha tocopherol and gamma- tocopherol. A 100 gr of walnut has 21 mg

gamma- tocopherol (Vitamin E), and this sum gives the 140% of day by day need. Vitamin E

is a solid fat-dissolvable cancer prevention agent. Vitamin E is expected to secure the bodily

fluid what's more, skin cell layers against the unsafe impacts of free radicals and to keep

their solidarity.

Walnut contains imperative Vitamin structures, for example, riboflavin, niacin, thiamine,

pantothenic acid, Vitamin B6, and folate/B9 (Sen SM., 2013). As walnut has a preventive

impacts of irritation, it diminishes the danger of hypertension; it additionally avoids blood

vessel ailments that can result with: heart, and cerebrum stroke, chest infections, colon and

prostate

malignancy (Marangoni et al., 2007; Amaral JS et al., 2003).

Walnut as fat, protein and carbs source

Walnut contains single and multi-unsaturated fat that influence the heart wellbeing.

4/3 of the calories in walnut are originating from fats. As it is known, 3 nourishment

supplements give calories: proteins, fats, and starches. Proteins what's more, sugars give 4

calories for each gram, though fats give 9 calories for each gram. Consequently, while

devouring hard shell organic products, we must be watchful about the measure of part and

we shouldn't eat excessively (Tapsell L et al., 2009; Sen S, 2011; Crews Cet al., 2005).
How walnut is consumed?

Walnut can be expended crude, natural, straightforwardly, yet in addition it very

well may be devoured as cooked, salted and enhanced. The inward piece of a walnut has a

wonderful taste, so it might be utilized as flavor enhancer in yogurt, pizza, cake or it very

well may be strewed on plate of mixed greens, dessert, particularly walnut dessert and

other frozen yogurts. One of the walnut wide applications is usage in sweet industry by

including rolls, cakes and sweets Minimal known certainty is that sweetened or chocolate-

secured walnut might be expended when is heaped on the highest point of the fish. Walnut

can be utilized as glue. Particularly, it is generally utilized by the general population who

have nut hypersensitivity.

In Middle-east nations, walnut is added to almond, date, grape, and used to set up a cake

called Mamoul in Ramadan (Sen S, 2011).

Other Walnut Properties

In their crude states, hypothetically, the greater part of the hard shell products of

the soil are the ideal sustenance stores. Walnut, which is the most significant of all hard

shell organic products, contains a lot of sound substances in crude and natural structure.

The most critical and remarkable nutritive attributes of walnut are sustaining and

supporting the mind and sensory system. Walnut can be considered as a nourishment
drugstore that keeps the unsafe wellbeing impact that can be brought about by different

sorts of sustenance, counting vegetables (Sen S, 2011).

When we devour enough walnut every day, we can see that walnut is an ideal malady

preventer. Because of its walnut taste and health advantages, walnut pastries have been

acknowledged for a large number of years.

Those who are utilizing walnut are very mindful of its different application as nourishment

added substance or unadulterated sustenance thing, and since it is known as an ideal mind

supplement, they can't live without it in their pockets and dinners. Today, we attempt to

learn and comprehend what and why it is deductively genuine. As referenced in western

sources, it is odd that the mind resembles a walnut. The harsh and hard shell of the walnut

resembles the skull (head) that encompasses the mind. Walnut inside is like mind. The two

piece of internal walnut resemble the two flaps of a mind. Individuals are passing the data

and encounters they acquired on walnut from past to today.A portion of the soaked and

unsaturated fat acids exist in specific sums in walnut. For the most part, there are 50 grams

(47.14) of multi-unsaturated fat acidsin 100 gr of walnut, and 40 grams (38.09 g) of it is

Omega 6 (llinoleic acid), and 10 grams (9.08 g) is Omega 3 (linolenic acid). The rate of

Omega 6 to Omega 3 in walnut is exceptionally low as for other hard shell nuts and it is a

positive quality (Sen, Ma Y et al., 2010).

Regarding nutritive esteem, walnut is better than pistachio, almond, hazelnut, pine nut, and

shelled nut. Vinson et al., (2012) clarifies it logically as: A bunch of walnut daily contains

multiple times a bigger number of cancer prevention agents and nutrients than other hard
shell nuts. Be that as it may, for the most part, individuals expend other hard shell nuts

aside from walnut. Truth be told, walnut must be incorporated into a sound sustenance

programs.

Metabolic effect on brain

The focal sensory system is metabolically requesting, expending about one-fourth of

all out oxygen admission and keeping for >20% of the metabolic rate very still (Hindman BJ

and Kochs E et al., 1993). The brain’s high metabolic rate results in the age of lopsided

measures of receptive oxygen and nitrogen species (Starke RM., 2013).

The harmful impacts of these free radicals are normally countered by endogenous

oxidoreductase chemicals and inherent proteins, which go about as atomic quenchers at

the cell level. In any case, maturing, just as different components, adjusts the homeostasis

between the age and extinguishing of these exceedingly receptive natural species,

prompting expanded oxidation at the cell level. Expanded oxidative pressure and lipid

peroxidation start a course of proinflammatory signs, prompting the dystrophy

furthermore, passing of mind cells. Adjusted homeostasis of oxidation, irritation, and

protein accumulation has been credited to the passing of neurons, which is

straightforwardly identified with hindrance in different subjective areas, for example,

learning, basic leadership, judgment, critical thinking, and memory (Joseph JA et al., 2005;
Yamazaki M et al., 1992; Sukitt-Hale B et al., 2004; Poulos SM et al., 2012). The coordination

and execution of subjective procedures relies upon the fitting recognition and proliferation

of signs from both the earth and encompassing cells in the cerebrum. The responsivity of

every cell relies upon the synthesis of the cell film, through which all signs must pass. FAs

are plentiful inside neuronal films, where they assume a job in keeping up basic

respectability, balancing catalyst movement, what's more, producing optional ambassadors

and other flagging atoms (Willis LM et al., 2009). The PUFA synthesis of neuronal layers

diminishes amid maturing and adds to the decay of neuronal work saw in maturing. This

modification is pervasive in the matured mind, especially the cortex, hippocampus,

striatum, and cerebellum, where decreased PUFA fixations add to changes in neuronal

morphology and a decline in layer smoothness and synaptic pliancy (Lopez GH et al., 1995;

Yehuda S et al., 2002; Mora F et al., 2007). Various neuronal capacities are influenced by

shortfalls in layer FA arrangement, all of which diminish the cells capacity to spread and

transmit motions inside the mind. In this way, expanded accessibility of PUFAs may

balance PUFA exhaustion in neuronal layers.

Weight and hypercholesterolemia and oxidative pressure assume an essential job in the

advancement of learning and memory disability (Farr SA et al., 2008; Ullrich C et al.; Evola

M et al., 2010]. Long haul utilization of high-fat eating routine or high vitality diet could

prompt heftiness and influence serum lipid levels and oxidative pressure, which thusly

influence
learning and memory capacities (Yim CY and Kosari Set al., 2012; Li J et al., 2010. The

conventional Mediterranean-style diet has less meats and sugars and more plant-based

sustenance and monounsaturated fat than an average American eating regimen. Following

the conventional Mediterranean-style diet may bring down the frequency and commonness

of learning and memory capacities (Yu H et al., 2010; Valls-Pedretet al., 2012). In such

manner, correlational examinations have affirmed that polyphenols add to the

counteractive action and treatment of learning and memory weakness (Spencer JP et al.;

Papandreou et al., 2009). Polyphenol removes from walnut testa contained polyphenols in

greater number (Ito H et al., 2007).

Oxidative pressure is a critical factor to the advancement of learning and memory

hindrance, which is known as the condition of awkwardness between the cell

reinforcement level and the creation of free radicals that instigates the cerebrum harm.

Oxygen free radicals are anything but difficult to amass in the cerebrum in view of its high

oxygen content, abnormal state of polyunsaturated unsaturated fats and low cancer

prevention agent resistance level (Butterfield DA et al., 2004). Overproduction of free

radicals will attract natural

macromolecules, for example, protein and nucleic acid capacities, and can change their

capacities and prompt lipid peroxidation, prompting cell passing (Khan RA et al., 2012)

Oxygen free radicals can be rummaged by cell reinforcements including SOD. MDA is a side-

effect of lipid peroxidation and is generally utilized as a biomarker of oxidative pressure

(Zhang SL et al., 2007). As of late, a few specialists have discovered that Walnuts contain
various possibly neuroprotective substances, for example, flavonoids and various

polyphenolics which have both mitigating and cell reinforcement properties and it is

demonstrated that utilization of these mixes has a defensive job against cisplatin-actuated

neurotoxicity without adjusting its enemy of tumor action (Fakuda T et al., 2003; Pribis P et

al., 2012). A prior investigation revealed that Polyphenolic mixes found in walnuts not just

decrease the oxidant and fiery burden on cerebrum cells yet additionally enhance

interneuronal flagging, increment neurogenesis, and improve sequestration of insoluble

lethal protein totals (Pouloseet al., 2014).

Walnut phytochemicals and in vitro studies:

Walnuts are a rich source of nutrients and bioactive phytochemicals. Walnuts contain large

amounts of PUFAs such as ALA and LA, which have been shown to boostbrain health and

function even with an increase in age (Willis LM et al., 2009; Buchsbaumet al., 1989). Every

100 g of walnuts(Juglansregia) contain 38 g of LA and 9 g of ALA, as well as 4.4 g of

saturated (palmitic acid, 16:0) and 8.7 g of monounsaturated(oleic acid, 18:1n–9) FAs. In

humans, ALA from walnuts is then converted through a series of sequential desaturation

and elongation reactions into essential PUFAs such as EPA (20:5n–3) and DHA (22:6n–3) in

the liver. Both EPA and DHA play an important role in brain health not only by reducing

oxidative stress and altering the immune function but also in maintaining synaptic
plasticity, neuronal membrane stability, gene expression, and neurogenesis (Willis et al.,

2009).

Despite the fact that PUFAs assume an imperative job in cerebrum wellbeing, the nearness

of other phytochemical parts adds to sound neuronal procedures.Other imperative

supplements in walnuts incorporate, yet are not constrained to, polyphenols, vitamin E,

folate, ellagitannins, ellagic acid monomers, polymeric tannins, melatonin, gelatin,

flavonoids, carotenoids, alkaloids, nitrogencontaining or on the other hand organosulfur

mixes, and an assortment of minerals.

Alongside PUFAs, different phytonutrients give direct neuroprotection (Bennel DK et al.,

2009; Ma Y et al.; McKay DL et al., 2010) just as aberrant assurance through enhanced lipid

profiles and endothelial capacityand expanded plasma cancer prevention agent limit.

Polyphenols present in walnuts incorporate, yet are not constrained to, hydroxycinnamic

acids for example, chlorigenic acid, caffeic acid, P-coumaric acid, ferrulic acid, and sinapic

acid; hydrobenzoic acids, for example, syringic acid what's more, ellagic acid; and mixes, for

example, gallic acid, glansrin, juglone, and syringaldehyde (Pariera JA et al., 2008).

Polyphenols advance neuronal calcium homeostasis in the striatum and hippocampus,

areas of the cerebrum significant for essential and optional memory capacities (Deivin BD

et al., 1996; Oleiveiraet al., 1997).Melatonin is another bioactive compound found in

walnuts. Endogenous melatonin, which is essentially blended by the pineal organ, assumes

a basic job in directingcircadian rhythms (Reiter RJ et al., 2005).

Melatonin inadequacy has been connected to degeneration of cholinergic neurons in the

basal forebrain and the affidavit of collected proteins, for example, amyloid b (Ab) peptides,

driving to subjective debilitation and dementia (Lahiri DK et al., 2005). Reiter et al. (2005)

revealed that utilization of walnuts expanded blood melatonin fixations, which related with

an expansion in ''absolute cell reinforcement limit'' of the serum with ''complete cancer

prevention agent limit,'' showing the capacity of the blood to detoxify free radicals. Walnut

extricate is neuroprotective against an assortment of stressors. Already, we demonstrated

that treating cells with walnut oil shielded the cells from increments in aggravation and

oxidative worry by hindering LPS-prompted initiation of microglial cells (Willis LM et al.,

2010). At the point when BV-2 mouse microglial cells were dealt with with walnut extricate

preceding LPS incitement, creation of NO also, articulation of inducible NO synthase were

significantly decreased. In a similar report, walnut extricate additionally diminished the

generation of TNF-an, a proinflammatory go between. We have additionally demonstrated

that calcium buffering in hippocampal cells was generously changed by LPS and 6-hydroxy

dopamine (DA) stressors (Joseph JA et al., 2010). Walnut remove ensured against LPS-

actuated, be that as it may, not DA-instigated, loss of calcium recuperation (Carey AN et al.,

2013). Another consider demonstrated that walnut extricate neutralized Ab-actuated

oxidative pressure and cytotoxicity in PC12 cells of rodent adrenal medulla (Muthaiyah B et

al., 2011).

In an ongoing report from our research center, we analyzed the cell components

fundamental walnuts defensive impacts on neuronal wellbeing and working in maturing

mind (Carey AN et al., 2013). Essential hippocampal neurons were pretreated with walnut

separate or with the PUFAs found in walnuts. The cells were at that point presented to DA

and LPS, and cell passing and calcium buffering dysregulation were estimated (Carey AN et

al., 2013).

Results showed that walnut oil concentrate, ALA, and DHA gave significant assurance

against cell demise and calcium dysregulation; the impacts were pretreatment focus ward

and stressor-subordinate.On the other hand, LA and EPA were not as compelling at

securing hippocampal cells from these affront. The entire walnut remove was most

valuable since it doesn't contribute the cell poisonous quality impacts. We have

additionally announced that PUFAs found in walnuts weaken neuro-inflammation by

adjusting microglial reactivity. In an investigation utilizing mouse microglial cells, walnut

remove adjusted the reaction boosts to the artificially initiated provocative worry through

phospholipase D2– intervened disguise of Toll-like receptor 4 (TLR-4) (Willis LM et al.,

2010).

Human Studies linked to Walnut studies:

Most human examinations partner walnuts and walnut PUFAs with their cardiovascular

advantages (Berrymen CE et al., 2013; West SG et al.; Sebet e J et al., 2010; Kris PM et al.,

2008). Decreases in cardiovascular infection hazard components might be related with

better mind wellbeing on the grounds that cardiovascular ailment is additionally connected

with the advancement of cerebrovascular illness, stroke, and mellow intellectual

impedance. A walnut-and walnut-oil– rich diet decreased fiery and cardiovascular hazard

factors amonghypercholesterolemic people (Zhao G et al., 2004). A walnutenriched diet can

likewise enhance endothelium-subordinate vasodilatation in sort 2 diabetic people (Ma Y

et al., 2010)

and overweight grown-ups with instinctive adiposity (Sanchez et al., 2011).

Expanded vasculature and made strides endothelial capacity have direct bearing on

cerebral wellbeing and psychological capacity. For the most part, expanded nut admission,

and walnut consumption in specific, has been appeared to enhance insight among more

established grown-ups. As of late,theDoetinchem Cohort Study detailed that higher nut

consumption at benchmark was related with progressed preparing speed, psychological

adaptability, memory, and worldwide subjective capacity (Nooyenset al., 2011). Another

huge, parallel-gathering, multicenter randomized, controlled clinical preliminary

(PREDIMED, Prevenci 'on con DietaMediterr'anea) as of late given convincing proof for the

capacity of nuts to check discouragement and agerelated subjective decay. This

investigation, spreading over 7 y with a base follow-up of 5 y, selected 7447 people (55– 80

y of age), with 3 randomized intercession arms (Sanchez et al., 2011). The principal

assemble got the Mediterranean eating regimen enhanced with virgin olive oil (1 L/wk),

the second gathering got the Mediterranean eating routine enhanced with 30 g/d of

blended nuts (15 g walnuts, 7.5 g almonds, 7.5 g hazelnuts), and the third gathering got a

low-fat control diet. After 3 y, members who were on the Mediterranean eating routine

supplemented with nuts had generously enhanced fixations of plasma mind determined
neurotrophic factor (BDNF), especially among the people with a background marked by

dejection (Sanchez et al., 2011). BDNF, a individual from the neurotrophin family, is very

communicated in cortical what's more, hippocampal neurons and advances the acceptance

of long term potentiation, synaptic versatility, neuronal survival and separation, axonal

extension, and synapse discharge (Bekenshetein P et al., 2008). BDNF can cross the blood-

cerebrum obstruction, and lower plasma what's more, mind BDNF protein fixations have

been involved in upgraded forcefulness, hyperactivity, and hyperphagia, also as in a variety

of cerebrum issue, for example, epilepsy, AD, Huntington sickness, chemical imbalance,

schizophrenia, andmajor discouragement (Lu B et al., 2013).

A subset of PREDIMED members were surveyed for neuropsychological testing, which

uncovered that higher admissions of both absolute olive oil what's more, virgin olive oil,

espresso, walnuts, and wine enhanced both memory and generally speaking intellectual

capacities. Moreover, the think about found that walnuts, among every single other nut

incorporated into the think about, were related with considerable enhancements in

working memory. The investigation likewise detailed that the Mediterranean eating

regimen with nuts decreased the danger of stroke by 46%, which in a roundabout way

builds up the advantages of nuts on age-relatedpsychological decay brought about by

vascular decay.Further supporting the advantages of walnuts on subjective work, Pribiset

al (2011) detailed that every day supplementation with 60 g of walnuts for 8

weekconsiderably enhanced inferential verbal thinking in a twofold visually impaired,

randomized, placebocontrolled traverse (6-wk washout) think about in youthful school

understudies. The investigation was led in sound, psychologically flawless youthful grown-

ups, which may clarify why no distinctions in memory, state of mind, or nonverbal thinking

were distinguished between the control and diet gathering. Walnuts may likewise assume a

job in avoiding AD. Dai et al. (Dai Q et al., 2006).

detailed that supplementation with foods grown from the ground juice, rich in polyphenols,

no less than multiple times/wk was credited to a slower beginning of AD, especially in

patients who are apoliproprotein e4 (APOE4) bearers (Lahiri DK et al., 2004). APOE4

assumes a basic job in advancing amyloid gathering, neurotoxicity, oxidative stress, and

neurofibrillary tangles. In 2 longitudinal partner thinks about, the Washington Heights and

InwoodColumbia Aging Undertaking (WHICAP; populace based) and the Predictors Study

(center based), which pursued individuals for a normal of 4 y, scientists demonstrated that

the nearness of somewhere around 1 APOE4 allele was related with quicker psychological

decrease in the soonest phases of AD (Cosentino S et al., 2008). In another investigation,

Yasunoet al. (2012) enhanced 41 members matured $65 y with n– 3 PUFAs from fish,

lycopene, and Ginkgo biloba removes day by day for 3 y furthermore, contrasted them and

622 members of a comparative age bunch without supplementation. They demonstrated

that the blend of cell reinforcements enhanced intellectual capacity in matured people after

3 y, and the enhancement in subjective capacity with supplementation was watched both in

APOE4 noncarrier (E42) and APOE4 bearer (E4+) gatherings (Yusanoet al., 2012). Despite

the fact that n– 3 PUFAs from creature sources vary from n– 3 PUFAs from walnuts, since

people convert ALA from walnuts into EPA what's more, DHA, it tends to be construed that
walnuts rich in n– 3 PUFAs, in mix with other high-cell reinforcement mixes, may postpone

the subjective decrease related with AD.

Taking everything into account, age-related increments in oxidative pressure furthermore,

irritation, particularly when combined with metabolic furthermore, cardiovascular

brokenness, lead to neurodegeneration and subjective decrease. This procedure of

cerebrum maturing happens even in the nonattendance of explicit neurodegenerative

maladies. Albeit most interminable neurodegenerative maladies cannot at present be

relieved, preventive estimates prior in life can ensure intellectual capacity in maturity and

may avoid or defer the beginning of crippling neurodegenerative illnesses. Dietary

mediations give a safe

furthermore, acceptable methods for adjusting the body’s inner condition furthermore,

significantly, the neuronal condition inside the brain. Walnut polyphenols and tocopherols

can lessen oxidative stress and irritation; moreover, PUFAs help keep up neuronal film

trustworthiness and weaken protein conglomeration associated with AD.

In rat contemplates, the expansion of dietary walnuts, comparable to a solitary serving of

walnuts for people, was adequate to enhance both engine and psychological conduct in

matured creatures. In people, the consideration of walnuts in the eating regimen enhanced

cardiovascular wellbeing, which is itself a hazard factor for neurodegenerative illnesses

and age-related intellectual decay. Taken together, this proof proposes that the

coordination of walnuts into a sound diet could be successful methods for dragging out
wellbeing ranges, abating the procedures of cerebrum maturing, and lessening the danger

of endless neurodegenerative ailment.

CONCLUSION:

English walnuts are rich in α-linolenic acid (ALA; 18:3n23) and linoleic acid (LA;

18:2n26) just as different polyphenolics, phytosterols, and micronutrients. Feeding studies

from our research facility have appeared dietary supplementation with walnuts can

enhance memory, cognizance, and engine work in matured creatures. The vast majority of

these examines have connected walnuts impacts to their high PUFA content, walnuts

notable polyphenol content assumes an essential job in decreasing the aggravation and

oxidative worry in the maturing mind. This survey tends to contemporary investigation

into the impacts of dietary walnuts on comprehension, engine work, and cerebrum

wellbeing. Although there exists an urgent need to develop effective treatments for age-

related cognitive decline and neurodegenerative disease, prevention strategies have been

underdeveloped. Primary prevention in many of these neurodegenerative diseases could

be achieved earlier in life by consuming a healthy diet, rich in antioxidant and anti-

inflammatory phytochemicals, which offers one of the most effective and least expensive

ways to address the crisis.

LITERATURE CITED
 Thies, W.,Bleiler, L. (2011). Alzheimer’s disease facts and figures. Alzheimer’s Marx, J.

(2006). Neurodegenerative diseases: picking apart the causes of mysteriousdementias.

Science, 314, 342.

Floyd, R.A., Hensley, K. (2002). Oxidative stress in brain aging: implications for

therapeutics of neurodegenerative diseases. Neurobiol Aging, 23, 807-795.

Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., Bennett, D.A., Aggarwal, N.,

Wilson, R.S.Scherr, P.A. (2002). Dietary intake of antioxidant nutrients and the risk of

incident Alzheimer disease in a biracial community study.JAMA, 287, 7-3230.

Scarmeas, N., Stern, Y., Tang, M.X., Mayeux, R., Luchsinger, J.A. (2006).

Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol, 59, 21-912.

Nooyens, A.C.J., Bueno-de-Mesquita, H.B., van Boxtel, M.P.J., van Gelder, B.M.,

Verhagen, H., Verschuren,W.M.M.(2011). Fruit and vegetable intake and cognitive decline

in middle-aged men and women: theDoetinchem Cohort Study. Br J Nutr, 106, 752-61.

Willis, L.M., Shukitt-Hale, B., Joseph, J.A. (2009). Modulation of cognition and

behavior in aged animals: role for antioxidant- and essential fatty acid rich plant foods. Am J

ClinNutr, 89, 1602S–6S.

Willis, L.M., Shukitt-Hale, B., Cheng, V., Joseph, J.A. (2009). Dose-dependent effects of

walnuts on motor and cognitive function in aged rats. Br J Nutr,101, 4-1140.

Shukitt-Hale, B., Lau, F.C., Joseph, J.A. (2008). Berry fruit supplementation and the

aging brain. J Agric Food Chem, 56, 41-636.

 Sen, S. M. (2013). Walnut Diet, Eating Walnut LivingHealthy (in Turkish). Alper

Publishing,216S.

Sen, S. M. (2011). Walnut, cultivation, nutritional value, folklore. ICC Publication, 4,

220.

Marangoni, F., Colombo, C., Martiello, A., Poli, A., Paoletti, R., Galli, C. (2007). Levels

of the n–3 fatty acid eicosapentaenoic acid in addition to those of alpha linolenic acid are

significantly raised in blood lipids by the intake of four walnuts a day in humans. Nutr.

Metab. Cardiovasc. Dis., 17 (6), 457-461.

Amaral, J.S., Casal, S., Pereira, J.A., Seabra, R.M., Oliveira, B. P. P. (2003).

Determination of sterol and fatty acid compositions, oxidative stability, and nutritional

value of six walnut (Juglansregia L.) cultivars grown in Portugal. J. Agric. Food Chem., 51,

7702-7698.

Tapsell, L., Batterham, M., Tan, S.Y., Warensjö, E. (2009). The effect of a calorie

controlled diet containing walnuts on substrate oxidation during 8-hours in a room

calorimeter. Journal of the American College of Nutrition, 28(5), 611-617.

Sen, S.M. (2011). Walnut, cultivation, nutritional value, folklore. ICC Publication, 4,

220.

Crews, C., Hough P., Godward J., Brereton P., Lees M., Guiet S., Winkelmann W.

(2005). Study of the main constituents of some authentic walnut oils. J. Agric. Food Chem.,

53, pp. 4853-4860

 Ma, Y., Njike, V.Y., Millet, J., Dutta, S., Doughty, K., Treu, J.A., Katz, D.L. (2010). Effects

of walnut consumption on endothelial function in type 2 diabetic subjects: a randomized

controlled crossover trial. Diabetes Care, 227-232.

Vinson, J.A., Cai, Y. (2012). Nuts, especially walnuts, have both antioxidant quantity

and efficacy and exhibit significant potential health benefits. Food Funct., 3(2), 134-40.

Hindman, B.J., Dexter, F., Cutkomp, J., Smith, T., Tinker, J.H. (1993). Hypothermic

acid-base management does not affect cerebral metabolic rate for oxygen at 27 degrees C: a

study during cardiopulmonary bypass in rabbits. Anesthesiology, 79, 580-7.

Kochs E, Hoffman WE, Werner C, Albrecht RF, Schulte am Esch J. (1993). Cerebral

blood flow velocity in relation to cerebral blood flow, cerebral metabolic rate for oxygen,

and electroencephalogram analysis duringisoflurence anesthesia in dogs. AnesthAnalag, 76,

1222-6.

Starke, R.M., Chalouhi, N., Ali, M.S., Jabbour, P.M., Tjoumakaris, S.I., Gonzalez, L.F.,

Rosenwasser, R.H., Koch, W.J., Dumont, A.S. (2013). The role of oxidative stress in cerebral

aneurysm formation and rupture. Curr Neurovasc Res, 10, 247–55.

Joseph, J.A., Shukitt-Hale, B., Casadesus, G. (2005). Reversing the deleterious effects

of aging on neuronal communication and behavior: beneficial properties of fruit

polyphenolics compounds. Am J ClinNutr, 81, 313S–6S.

Yamazaki, M., Araki, T., Imazu, O., Kitamura, S., Terashi, A. (1992). A case of

Machado-Joseph disease–cerebral blood flow and cerebral metabolic rate of oxygen.

RinshoShinkeigaku, 32, 755-7.

 Shukitt-Hale, B., McEwen, J.J., Szprengiel, A., Joseph JA. (2004). Effect of age on the

radial arm water maze—a test of spatial learning and memory.Neurobial Aging, 25, 223-9).

Poulose, S.M., Carey, A.N., Shukitt-Hale, B. (2012). Improving brain signaling in

aging: could berries be the answer? Expert Rev Neurother. 12, 887-9.

L´ opez, G.H., Ilincheta, de Boschero, M.G., Castagnet, P.I., Giusto, N.M. (1995). Age

associated changes in the content and fatty acid composition of brain glycerophospholipids.

Comp BiochemPhysiol B BiochemMolBiol, 112, 331–43.

Yehuda, S., Rabinovitz, S., Carasso, R.L., Mostofsky, D.I. (2002). The role of

polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurobiol Aging, 23,

843–53.

Mora, F., Segovia, G., del Arco, A. (2007). Aging, plasticity and environmental

enrichment: structural changes and neurotransmitter dynamics in several areas of the

brain. Brain Res Rev, 55, 78–88.

Farr ,SA., Yamada, K.A., Butterfield, D.A., Abdul, H.M., Xu, L., Miller, N.E., & Morley, J.E

(2008). Obesity and hypertriglyceridemia produce cognitive impairment. Endocrinology,

149 (5), 2628-2636.

Ullrich, C., Pirchl, M., Humpel, C., Hypercholesterolemia in rats impairs the

cholinergic system and leads to memory deficits. (2010). Molecular and cellular

neuroscience, 45 (4), 408-417.

 Evola, M., Hall, A., Wall, T., Young, A., & Grammas, P. (2010). Oxidative stress impairs

learning and memory in apoE knockout mice. Pharmacology biochemistry and behavior, 96

(2), 181-186.

Yim, C.Y., Soczynska, J.K., Kennedy, S.H., Woldeyohannes, H.O., Brietzke, E., McIntyre,

R.S. (2012). The effect of overweight/obesity on cognitive function in euthymic individuals

with bipolar disorder. European psychiatry, 27(3), 223-228.

Kosari, S., Badoer, E., Nguyen, J.C., Killcross, A.S., Jenkins, T.A. (2012). Effect of

western and high fat diets on memory and cholinergic measures in the rat. Behavioural

brain research, 235(1), 98-103.

Li, J., Wang, C., Zhang, J.H., Cai, J.M., Cao, Y.P., Sun, X.J. (2010). Hydrogen-rich saline

improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by

reduction of oxidative stress. Brain research, 1328, 152-161.

Yu, H., Bi, Y., Ma, W., He, L., Yuan, L., Feng, J., Xiao, R. (2010). Long-term effects of high lipid

and high energy diet on serum lipid, brain fatty acid composition, and memory and learning

ability in mice. International journal of developmental neuroscience, 28 (3), 271-276.

Valls-Pedret, C., Lamuela-Raventós, R.M., Medina-Remón, A., Quintana, M., Corella,

D., Pintó, X., Ros, E. (2012). Polyphenol-rich foods in the Mediterranean diet are associated

with better cognitive function in elderly subjects at high cardiovascular risk. Journal of

Alzheimer's disease, 29 (4), 773-782.

 Spencer, J.P., Vauzour, D., Rendeiro, C. (2009). Flavonoids and cognition: the

molecular mechanisms underlying their behavioural effects. Archives of biochemistry and

biophysics, 492 (1), 1-9.

Papandreou, M.A., Dimakopoulou, A., Linardaki, Z.I., Cordopatis, P., Klimis-Zacas, D.,

Margarity, M., Lamari, F.N. (2009). Effect of a polyphenol-rich wild blueberry extract on

cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity.

Behavioural brain research, 198 (2), 352-358.

Ito, H., Okuda, T., Fukuda, T., Hatano, T., Yoshida, T. (2007). Two novel dicarboxylic

acid derivatives and a new dimeric hydrolyzable tannin from walnuts. Journal of

agricultural and food chemistry, 55 (3), 672-679.

Butterfield, D.A., Drake, J., Pocernich, C., Castegna, A. (2001). Evidence of oxidative

damage in Alzheimer's disease brain: central role for amyloid β-peptide. Trends in

molecular medicine, 7(12), 548-554.

Khan, R.A., Khan, M.R., Sahreen, S. (2012). Protective effects of rutin against

potassium bromate induced nephrotoxicity in rats. BMC complementary and alternative

medicine, 12 (1), 204.

Zhang, X.L., Jiang, B., Li, Z.B., Hao, S., An, L.J. (2007). Catalpol ameliorates cognition

deficits and attenuates oxidative damage in the brain of senescent mice induced by D-

galactose. Pharmacology biochemistry and behavior, 88 (1), 64-72.

Fukuda, T., Ito, H., & Yoshida, T. (2003). Antioxidative polyphenols from walnuts

(<i>Juglansregia</i> L.). Phytochemistry, 63 (7), 795-801.

 Pribis, P., Bailey, R.N., Russell, A.A., Kilsby, M.A., Hernandez, M., Craig, W.J., &Sabate,

J. (2012). Effects of walnut consumption on cognitive performance in young adults. British

journal of nutrition, 107 (09), 1393-1401.

Poulose, S.M., Miller, M.G., &Shukitt-Hale, B., Role of walnuts in maintaining brain

health with age.(2014). The journal of nutrition, 144 (4), 561S-566S.

Willis, L.M., Shukitt-Hale, B., Joseph,J.A.(2009). Modulation of cognition and behavior

in aged animals: role for antioxidant- and essential fatty acidrich

plant foods. Am J ClinNutr., 89, 1602S–6S.

Buchsbaum, M.S., Gillin, J.C., Wu, J., Hazlett, E., Sicotte, N., Dupont, R.M. Bunney,

W.E.Jr.(1989). Regional cerebral glucose metabolic rate in human sleep assessed by

positron emission tomography. Life Sci, 45, 1349–56.

Willis, L.M., Shukitt-Hale, B., Joseph,J.A.(2009). Dietary polyunsaturated fatty

acids improve cholinergic transmission in the aged brain. Genes Nutr, 4, 309–14.

Banel, D.K., Hu, F.B. (2009). Effects of walnut consumption on blood lipids and other

cardiovascular risk factors: a meta-analysis and systematic review. Am J ClinNutr, 90, 56–

63.

Ma, Y., Njike, V.Y., Millet, J., Dutta, S., Doughty, K., Treu, J.A., Katz, D.L. (2010) Effects

of walnut consumption on endothelial function in type 2 diabetic subjects: a randomized

controlled crossover trial. Diabetes Care, 33, 227–32.

 McKay, D.L., Chen, C.Y., Yeum, K.J., Matthan, N.R., Lichtenstein, A.H., Blumberg, J.B.

(2010). Chronic and acute effects of walnuts on antioxidant capacity and nutritional status

in humans: a randomized, cross-over pilot study. Nutr J, 9, 21.

Tapsell, L.C., Gillen, L.J., Patch, C.S., Batterham, M., Owen, A., Bare, M., Kennedy, M.

(2004). Including walnuts in a low-fat/modified-fat diet improves HDL cholesterol-to-total

cholesterol ratios in patients with type 2 diabetes. Diabetes Care, 27, 2777–83.

Pereira, J.A., Oliveira, I., Sousa, A., Ferreira, I.C., Bento, A., Estevinho, Bioactive

properties and chemical composition of six walnut (Juglans Devan, B.D., Goad, E.H., Petri,

H.L. (1996). Dissociation of hippocampal and striatal contributions to spatial navigation in

the water maze. Neurobiol Learn Mem, 66, 305–23.

Oliveira, M.G.M., Bueno, O.F.A., Pomarico, A.C., Gugliano, E.B.(1997). Strategies used

by hippocampal- and caudate-putamen-lesioned rats in a learning task. Neurobiol Learn

Mem, 68, 32–41.

Reiter, R.J., Manchester, L.C., Tan, D.X. (2005). Melatonin in walnuts: influence on

levels of melatonin and total antioxidant capacity of blood. Nutrition, 21, 920-4.

Lahiri, D.K., Chen, D.M., Lahiri, P., Bondy, S., Greig, N.H. (2005). Amyloid,

cholinesterase, melatonin, and metals and their roles in aging and neurodegenerative

diseases. Ann N Y AcadSci, 1056, 430–49.

Willis, L.M., Bielinski, D.F., Fisher, D.R., Matthan, N.R., Joseph,J.A.(2010). Walnut

extract inhibits LPS-induced activation of BV-2 microglia via internalization of TLR4:

possible involvement of phospholipase D2. Inflammation, 33, 325–33.

 Joseph, J.A., Shukitt-Hale, B., Brewer, G.J, Weikel, K.A., Kalt, W., Fisher,D.R.(2010).

Differential protection among fractionated blueberry polyphenolics families against DA-,

Abeta(42)- and LPS-induced decrements in Ca(2+) buffering in primary hippocampal cells. J

Agric Food Chem, 5, 8196–204.

Carey, A.N., Fisher, D.R., Joseph, J.A., Shukitt-Hale, B. (2013). The ability of walnut

extract and fatty acids to protect against the deleterious effects of oxidative stress and

inflammation in hippocampal cells. NutrNeurosci, 16, 13–20.

Muthaiyah, B., Essa, M.M., Chauhan, V., Chauhan, A. (2011). Protective effects of

walnut extract against amyloid beta peptide-induced cell death and oxidative stress in

PC12 cells. Neurochem Res ,36, 103-2096.

Berryman, C.E., Grieger, J.A., Wes,t S.G., Chen, C-YO., Blumberg, J.B., Rothblat, G.H.,

Sankaranarayanan, S., Kris-Etherton, P.M. (2013). Acute consumption of walnuts and

walnut components differentially affect postprandial lipidemia, endothelial function,

oxidative stress, and cholesterol efflux in humans with mild hypercholesterolemia. J Nutr.

143, 94-788.

West, S.G., Krick, A.L., Klein, L.C., Zhao, G., Wojtowicz, T.F., McGuiness, M., Bagshaw,

D.M., Wagner, P., Ceballos, R.M., Holub, B.J. (2010). Effects of diets Walnut effects on brain

health high in walnuts and flax oil on hemodynamic responses to stress and vascular

endothelial function. J Am CollNutr, 29, 595–603.

Sabat´e, J., Oda, K., Ros, E. (2010) Nut consumption and blood lipid levels: a pooled

analysis of 25 intervention trials. Arch Intern Med, 7-821.

 Kris-Etherton, P.M., Hu, F.B., Ros, E., Sabate,J.(2008). The role of tree nuts and

peanuts in the prevention of coronary heart disease: multiple potential mechanisms. J Nutr.

138, 1746S–51S.

Zhao, G., Etherton, T.D., Martin, K.R., West, S.G., Gillies, P.J., Kris-Etherton,

P.M.(2004). Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk

factors in hypercholesterolemic men and women. J Nutr., 134., 2991-7.

Ma, Y., Njike, V.Y., Millet, J., Dutta, S., Doughty, K., Treu, J.A., Katz,D.L.(2010) Effects of

walnut consumption on endothelial function in type 2 diabetic subjects: a randomized

controlled crossover trial. Diabetes Care, 33, 32-227.

S´anchez-Villegas, A., Galbete, C., Martinez-Gonzalez, M.A., Martinez, J.A., Razquin, C.,

Salas-Salvado, J., Estruch. R., Buil-Cosiales, P., Marti A (2011). The effect of the

Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: the

PREDIMED-NAVARRA randomized trial. NutrNeurosci, 14, 195–201.

Nooyens, A.C.J., Bueno-de-Mesquita,H.B., van Boxtel, M.P.J., van Gelder,

B.M,,Verhagen, H., Verschuren, W.M.M.(2011). Fruit and vegetable intake and cognitive

decline in middle-aged men and women: theDoetinchem Cohort Study. Br J Nutr, 106, 61-

752.

Bekinschtein, P., Cammarota, M., Izquierdo, I., Medina,J.H.(2008). BDNF and Lu, B.,

Nagappan, G., Guan, X., Nathan, P.J., Wren,P.(2013). BDNF-based synaptic repair as a

disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci, 14, 401-16.
 Pribis, P., Bailey, R.N., Russell, A.A., Kilsby, M.A., Hernandez, M., Craig, W.J., Grajales,

T., Shavlik, D.J., Sabate,J.(2011). Effects of walnut consumption on cognitive performance in

young adults. Br J Nutr., 19, 1-9.

Dai, Q., Borenstein, A.R., Wu, Y., Jackson, J.C., Larson, E.B.(2006). Fruit and

vegetable juices and Alzheimer’s disease: The Kame Project. Am J Med, 119, 9-751.

Lahiri, D.K. (2004). Apolipoprotein E as a target for developing new therapeutics for

Alzheimer’s disease based on studies from protein, RNA, and regulatory region of the gene.

J MolNeurosci, 23, 225-33.

Cosentino, S., Scarmeas, N., Helzner, E., Glymour, M.M., Brandt, J., Albert, M., Blacker,

D., Stern,Y.(2008). APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer

disease. Neurology, 70, 1842-9.

Yasuno, F., Tanimukai, S., Sasaki, M., Ikejima, C., Yamashita, F., Kodama, C., Mizukami,

K., Asada,T.(2012). Combination of antioxidant supplements improved cognitive function in

the elderly. J Alzheimer Dis., 32, 895–903.