Inspire Student Journal Autumn 2023

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ReviewMEDICINEThe potential use of food therapy tomodulate cognitive declineAisha ElahiYear 3, Medicine, University of PlymouthEmail: aisha.elahi@students.plymouth.ac.ukAbstractThe incidence of cognitive diseases such as Alzheimer’s Dementia isexpected to grow and the impacts of these diseases on wellbeing isdrastic, therefore requires exploration of contributing factors for theirdevelopment as well as investigation of potential therapies. Some ofthese are available in food sources and already available for clinicaluse. This literature review discusses some of the mechanisms ofspecific chemicals modulators that prevent neurogenerative decline(mainly polyphenols such as resveratrol, curcumin, flavonoids andEGCG) as well as oral health and food texture which may influencecognitive function.The main findings are that polyphonic compounds are effective atreducing oxidative stress and, subsequently, Aβ plaque formation, ahallmark of Alzheimer’s Dementia. Greater chewing force was relatedto reduction in stress hormones, depression and central nervoussystem changes.AbbreviationsAD – Alzheimer’s diseaseAPP – Amyloid precursor proteinEGCG – Epigallocatechin gallateMDA – MalondialdehydeNAD – Nicotinamide adenine dinucleotideNAPP – N-terminal amyloid precursor proteinNMDA – N-methyl-D-aspartateROS – Reactive oxygen speciesSGZ – Subgranular zoneSIRT – SirtuinsSVZ – Subventricular zoneIntroductionNeurogenesis is the process of new neurons being formed in thebrain. Previously, neurogenesis had been thought to have stoppedin the adult brain but is now widely accepted to continue in adults. 1Adult neurogenesis mainly occurs in the subventricular zone,subgranular zone and dentate gyrus of the hippocampus, 2 an areathat functions to form and consolidate memories and makes uppart of the limbic system which functions to influence mood. Thisarea of the brain is majorly affected in Alzheimer’s disease causingthe symptoms of memory loss and depression, so protection of thisarea is vital to prevent instances and progression of the disease. 3 Thisarticle explores how altering diet may protect the hippocampus andthe interactions between the food we eat and neurogenesis.MethodsTo investigate the potential use of food as a diagnostic and protectivemeasure against cognitive decline, literature searches were carriedout on PubMed and Google Scholar to specify dietary componentsthat have been implicated in neurology, mainly their oxidative stressmitigation. Less researched areas, such as the effects of EGCG andchewing, were explored via citation chaining and Google Scholar.Articles included were chosen to cover a range of dietary factors,components and composition, to emphasise different elements ofdiet as well as research that already has clinical implications to furthervalidate usage.ResultsThe search initially found 14 articles, however, eight were removedas they were not specific to dietary content or hippocampalneurogenesis in adults.DiscussionThe role of oxidative stress in cognitive declineOne contributor to cognitive decline is oxidative stress which exertsits effects via a plethora of mechanisms. 4 One such mechanism isAβ metal ion redox potential whereby metal ions such as zinc 2+ andiron 3+ bind to the ends of Aβ peptides producing high numbersof reactive oxygen species (ROS) and promoting pathologicalInspire Student Health Sciences Research Journal | Autumn 202324
plaque development. These ROS then produce a positive feedbackloop of oxidation and ROS production, creating a self-sustainingenvironment in which neuronal cell death is imminent. This is partlybecause increases of ROS in the brain negatively affect the enzymesglutamine synthetase and creatine kinase 5 leading to damage tothe brain. Glutamate synthetase reduces levels of glutamate inthe brain however, when oxidised, the enzyme is unable to carryout its function causing a build-up of glutamate. 6 The higher levelof glutamate activates NMDA receptors in the surrounding extrasynapticregion of the postsynaptic neuron which then overcomethe protective measures of NMDA receptors in the synaptic regionleading to excitotoxicity and eventual neuronal cell death. 7 Creatinekinase plays a key role in regulating ATP levels in neural cellstherefore its oxidation, and subsequent damage, leads to reducedenergy metabolism contributing to cell death. Therefore, oxidativestress and ROS production play major roles in the development ofAlzheimer’s disease and cognitive decline: aiming to reduce theeffects of oxidative stress by modulating the number of ROS may bebeneficial to those afflicted.Polyphonic protection of neurons and cognitive declineMultiple studies 8 show polyphenols, found naturally in plants, havethe ability to directly stimulate neuronal cell proliferation, reduceeffects of oxidative stress and attenuate inflammation. For example,resveratrol (RSV), found in grapes and red wine, is a highly studiedpolyphenol that is able to induce beneficial effects to the brain byactivating sirtuins (SIRTs). 9 These are regulatory enzymes involvedin a variety of functions including metabolism and brain function,which primarily work by editing histones to prevent DNA damage.SIRTs increase the content of NAD in cells, which increases energyproduction, thereby enabling greater cell survival, synaptic plasticityand neuronal stress resistance. 10 One study 11 found SIRT1 activationreduced tau protein phosphorylation, premature cell death andsynaptic loss in the brains of pathological mice models. This hadthe downstream effect of reducing behavioural deficits, hencesupporting the use SIRT1 activation as a therapeutic method forAD and other neurological conditions. Furthermore, resveratrol isable to reduce ROS, scavenge free radicals and upregulate enzymessuch as glutathione peroxidase, which protects cells from oxidativedamage, therefore the properties of resveratrol allow it to producepowerful antioxidant effects. Additional actions include inhibitingpro-inflammatory mechanisms such as tumour necrotic factor-αproduction and cytokine release, indicating that resveratrolcould produce positive clinical effects in patients suffering fromneurological conditions. 12 However, resveratrol has low bioavailabilityin humans and little work has been done to tackle this problem forclinical use. 13 Additionally, the bioavailability measurements maybe inaccurate as the distribution to other tissues is not considered.Hence, future research needs to fully explore targeted therapy inorder to fully utilise the benefits of resveratrol and make use of it ina clinical setting.Like resveratrol, curcumin can reduce oxidative stress andinflammatory responses in the brain to prevent damage. It is alsouseful to diagnose Alzheimer’s disease at an earlier stage through itsability to bind to Aβ plaques and produce a strong fluorescent signal,making it useful for positron emission tomography (PET), magneticresonance imaging (MRI) 14 as well as other modalities. Its use hasalready been approved by the US Food and Drug Administration forclinical use and earlier diagnosis allows for patients to plan ahead. Itgives people greater autonomy when making decisions about theirhealthcare while they have capacity and increases the opportunityto live independently. 15 Additionally, curcumin significantly reducedBACE-1 levels (an enzyme involved in Aβ plaque production) so itsinhibition prevents amyloid precursor protein maturation thus maybe used to provide therapeutic benefit in AD. 16 However, whenadministered orally, curcumin showed no difference in cognitiveimpairment amongst AD patients when trialled clinically which maybe due to low bioavailability. This mirrored the same problem asresveratrol hence these findings, again, emphasise the need to findmodalities to make polyphenols more available in the brain in orderto achieve therapeutic effects and for clinical use.Flavonoids are also implicated to be protective against dementiaand reverse some deficit in cognitive function. They have an abilityto interact with multiple pathways to produce resistance to oxidantsand inflammatory mediators and influence neuronal differentiation,long-term potentiation and memory. 17 Already there is evidencethat flavonoid intake is associated with improved cognitive functionin people aged 65 or over. For example, a study found intake offlavonoids produced better Mini-Mental State Examination scoresin a dose-dependent relationship over a 10-year period. 18 One modeflavonoids are able to exhibit neuroprotective effects is through theinhibition of β-secretase and activation of α-secretase. 19 β-secretaseis essential for the generation of β-amyloid plaques due its functionof cleaving APP into Aβ peptides and N-APP bringing aboutapoptotic destruction of neuronal cells 20 which are hallmarks of AD.Hence, inhibition of β-secretase would prevent cleavage of APP fromoccurring and reduce risk of plaque and disease development.EGCG, the main flavonoid in green tea, was investigated for its potentialtherapeutic effect on cognition. A study 21 conducted in Wuhan,China explored the relationship between green tea consumption andcognitive function in Chinese middle-aged and elderly people. Theresults showed individuals consuming green tea had significantlylower levels of tau proteins and Aβ peptide levels in comparison tothose who did not as well as lower levels of oxidative stress markersin serum, such as MDA, indicating green tea consumption mayreduce AD pathology through antioxidant mechanisms. ECGC is ableto produce neuroprotective effects through many mechanisms, oneof which is the increased expression of antioxidant enzymes suchas glutamate-cysteine ligase. 22 This enzyme produces glutathione,a major antioxidant, which is significantly lower in AD patients 23 soincreasing glutathione levels may be protective against oxidativestress. Additionally, ECGC is able to prevent hyperphosphorylationof tau proteins and accumulation of neurofibrillary tangles in thebrain via activation of the Akt signalling pathway. This functions toreduce tau hyperphosphorylation 24 , a key feature in AD therefore,supplementation with ECGC may increase antioxidant abilities inpatients and reduce abnormal build-up of these tangles.Importance of oral healthNot only does the contents influence dementia occurrence, themode of ingestion contributes to its progression. As people age, oralhealth reduces and they experience more oral problems that impairmastication such as dental caries, tooth loss and periodontal disease. 25This makes people more likely to opt for a softer diet 26 causing themto miss out on preventative measures such as nutrients sourcedin hard foods putting them at greater risk of malnutrition. Thoseexperiencing dental problems opt to avoid harder foods such asfruits and vegetables which exposes them to low grade inflammationand oxidative stress 27 , a major factor during pathological conditionssuch as Parkinson’s disease and AD. 28Impact of food texture on neuroprotectionThe action of chewing itself may also prevent dementia. Some studiesshow chewing increases blood oxygen level dependent signals inMRI scans in the primary sensorimotor cortex, cerebellum, thalamusand prefrontal cortex. 29 The prefrontal cortex is important for theconsolidation of memories in the hippocampus as information fromthe prefrontal cortex streams into areas of the hippocampus whereobjects and places are encoded within a context. 30 This informationcan then be retrieved and relayed back to the prefrontal cortex whenstimulated. This hippocampal-prefrontal relay system is impaired inAD and other cognitive impairments 31 , which partly explains whyaffected patients struggle to form new memories and retrieve oldmemories. Increased blood flow to this region serves as a protectiveforce to its degradation. Another investigation 32 explored the effectsof hard-diet feeding and soft-diet feeding on neurogenesis in theInspire Student Health Sciences Research Journal | Autumn 2023 25
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Inspire Student Journal Autumn 2023

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