OMEGA 3 FAs in the

ALZHEIMER’S DISEASE

(HFN- 690)

Maibam Baby DeviI.D No. 48048

M.Sc Foods & Nutrition2nd Year

Overview Introduction to alzheimer’s diseaseCauses & symptomsOmega 3 fatty acidsFunctionsMechanism of actionOmega 3 and alzheime’rs disease trialsSummaryFuture researchBibliographies

highlights

Prevention of age-related cognitive decline - a public health challenge.

Nutrition, a major lifelong environmental factor, offers promising perspectives.

Certain foods nourish the brain.

Long-chain PUFA are major components of neuron membranes.

HIGHLIGHTS

Irreversible, progressive brain disease that destroys memory and thinking skills.

Abnormal changes in the brain

Limited treatment options and no cure.

Memory loss leads to inability.

Death .

Studies found that omega-3 FAs protect against cognitive decline with advancing age.

Alzheimer’s disease -most common form of dementia. It is a neurological brain disorder named after a German physician, Alois Alzheimer, who first described it in 1906.

GLOBAL PREVELANCE

In 2010, there are 3.7 million

Indians with dementia and the

total societal costs is about

14,700 crore

While the numbers are expected

to double by 2030, costs would

increase three times

PREVELANCE

Source: Alzheimer’s and Related Disorders Society of India, New Delhi

State wise prevelance By 2026, more than 500,000 older people with dementia are

expected to be in Uttar Pradesh and Maharashtra.

Rajasthan, Gujarat, Bihar, West Bengal, Madhya Pradesh, Orissa, Andhra Pradesh, Karnataka, Kerala and Tamil Nadu- around 20,000 to 40,000 persons

Delhi, Bihar and Jharkhand are expected to experience 200% (or greater) increment .

Jammu and Kashmir, Rajasthan, Madhya Pradesh, West Bengal, Assam, Chhattisgarh, Gujarat, Andhra Pradesh, Haryana, Uttarakhand, Maharashtra, Karnataka and Tamil Nadu- 100%

source: Alzheimer’s and Related Disorders Society of India

Structure of brain and neurotransmitters

Billions of nerve cells in human brain.

Neurotransmssion- helps to communicate.

Nerve cells are made up of fat.

Phospholipid- 60% dry weight of the brain.

Phospholipid- synaptic structure, signal transduction.

Fewer nerve cells and synapses.

Damage of brain regions and neural circuits critical for memory and cognition.

Neo cortex, Hippocampus and the amygdala–affected.

The pathogenesis is complex.

CHARACTERISTICS

Modifiable factors

Vascular Disease

Hypertension

Diabetes

Dyslipidaemia

Stress

Diet

Non modifiable factorsAgeFamily history ApoE4 gene. Depression Head trauma Mutation

PATHOPHYSIOLOGY

1. Accumulation of amyloid beta (A β) plaques .

APP- glycoprotein for cell surface signaling molecule

Cleavage of APP by α, β/ γ secratase produce-amyloid β peptides.

Excessive AB- produces plaques.

Contd….

2. Neurofibrillary tangles: Insoluble twisted fibers inside the brain's cells.

tangles consist of a protein -tau, which forms part of a structure -microtubule.

“Hyperphosphorylation,” Tau disengages from the microtubules.

Paired helical filaments, which become enmeshed with another, forming tangles.

Microtubules disintegrate in the process, collapsing the neurons.

Damages the ability of neurons to communicate

Plaques and tangles -prime suspects.

1. Preclinical

2. Mild cognitive impairment

3. Dementia.

• deficits in spatial cognition, impaired face recognition.

• impaired reasoning, judgment, and problem solving.

THE MAIN SYMPTOMS

Early Onset Alzheimer’s

Between the ages of 30 and 60 years

Young-onset, accounting 5%

Mutations in APP, PS1, and PS2.

Presenilin’s are crucial components of the enzymes that work to cleave APP.

mutations in presenilins cause the production of a-beta42 and a-beta43 peptides (insoluble forms of a-beta)

PRESENILINS

No specific gene mutations.

Specific alleles of apoliprotein e4 (APoE4)

- APoE4- transport of transport of cholesterol, other lipids involve in brain composition.

Evidence indicates that genetic variability in A-beta catabolism and clearance may contribute.

LATE ONSET ALZHEIMER’S

STRUCTURE Alpha-linolenic

acid (ALA) Eicosapentaenoi

c acid (EPA) Docosahexaenoi

c acid (DHA)

Omega 3 fatty acids

SOURCESALA• Flaxseed 18.1% • Hempseed 8.7%• Butterfruits- 8.7%• walnuts- 6.3%• Hazel nuts -0.1%

Research suggests that only a small amount can be synthesized in the body from this process.

Cell membrane fluidity

Modulation of neurotransmitters,

Signal transduction pathways

Healthy cell growth

Potent anti-inflammatories

Hormone production, protecting the immune system,

Healthy vision and brain development and function.

Impact on serotonin and dopamine transmission.

Decreased intake increases the risk of several psychiatric disorders.

FUNCTIONS

Disease Prevention:

Impaired Visual and Neural Development

Coronary Heart Disease

Sudden Cardiac Death Cancer Diabetes Mellitus Inflammatory Diseases

Rheumatoid arthritis

Inflammatory Bowel DiseaseUlcerative colitis and Crohn’s Disease

Asthma

Depression & Bipolar Disorder

Schizophrenia

DHA comprising 60% in neuronal cell membranes, smaller amounts of EPA.

Gray matter of the cortex, 30–40% of the FAs are DHA , with high concentrations in synaptic membranes.

Brain development

Required for normal brain functions : neurotransmission, synaptic plasticity.

Omega 3 fatty acids in the brain

Acts as structural components of nerve cells membranes and as regulators of inflammation.

Slow the accumulation of 2 proteins associated with plaques and tangles.

Increases the production of LR11- Can destroy the protein which forms plaques.

Regulates synaptic membrane proteins in synaptic plasticity and improves executive functions and learning abilities.

Lower β-amyloid 42 (Aβ 42) plasma levels, higher total brain and hippocampal volume.

Higher LC-n3-FA consumption correlates with better cognitive functioning ,a reduced risk for dementia.

MECHANISM OF ACTION

Changing the fatty acid composition leads to functional changes in the activity of receptors.

Amount of DHA can affect the molecular structure and fluidity of the membrane.

Dearrangements in neuronal metabolism if deficient.

Contd….

Protect amyloid-β production, neurofibrillary tangles.

Prevents membrane disorganization by incresing neuronal survival.

Difficult to get EPA and DHA through diet

ALA is a prominent component of our diet

ALA does not provide the health benefits seen with EPA

SUPPLEMENTATION

Source: Omega-3 fatty acids | University of Maryland Medical Center

Based on the amount of EPA and DHA Omega-3 fatty acids in fish oil capsules is 0.18 grams (180 mg) of EPA and 0.12 grams (120 mg) of DHA. Children (18 years and younger)

no established dose for children.

Adults- NOT more than 3 grams daily.

How to Take It

FAO⁄WHO, recommended dose is 5–10:1 (n-6:n-3), but this dose was not established on the basis of different serum DHA and EPA.

Their efficacy is dependent upon the ratio of n-6:n-3 and the condition being treated.Lower ratios between 2.5:1(n-6:n-3) and 5:1(n-6:n-3) are beneficial.

Daily intake of 2.5:1(n-6:n-3) has been proven to act beneficially in cases of colorectal cancer, 2–3:1(n-6:n-3) on rheumatoid arthritis, and 5:1(n-6:n-3) on asthma.For AD has to be determined

RESEARCH TO RECOMMENDATIOS

Omega-3 fatty acids do not interact with most other medications.

Increased risk of bleeding eg; hemophilia Stomach upset, change in the bowel movements

JOIN ALZHEIMER’S DISEAE RESEARCH

RESEARCHStudy Omega 3 Fatty

Acids AmountsFindings

Freund-Levi et al.

DHA (1.7 g/d) and EPA (0.6 g/d)

Decline in cognitive function did not differ between supplemented group and control group at 6 mo. However, patients with very mild cognitive dysfunction in the EPA+DHA-supplemented group had a significant reduction in decline rate at 6 mo

Vedin et al DHA (1.7 g/d) and EPA (0.6 g/d)

Supplementation was associated with decreased levels of IL-1b, IL-6, stimulating factor at 6 mo

Study Omega 3 fatty acids amounts

Major findings

Irving et al. DHA (1.7 g/d) and EPA (0.6 g/d) for 6 mo

Supplementation was associated with positive weight gain and appetite in supplementation group at 6 mo, but not in the control group, and for both groups at 12 mo

Quinn et al. DHA (2 g/d for 18 mo)

DHA supplementation lead to no beneficial effect on rate of cognitive and functional decline

The greater life expectancy translates into a high lifetime risk of cognitive decline and dementia Omega-3 FAs could play an important role in maintaining cognitive function in aging individuals. The omega-3 FA DHA is a major constituent of neuronal membranes and is essential for normal brain development.

Blood levels of DHA /EPA are decreased in individuals with AD, suggesting that deficiency could contribute to cognitive impairment.

 In vitro studies, omega-3 fa have been shown to have a wide variety of beneficial effects on neuronal functioning, inflammation, oxidation and cell death.

Protect against the development of cognitive impairment.

Supplementation - not only reverses this deficiency, but may also improve cognitive function.

EPA and DHA may be a safe and inexpensive link to a healthier life.

1. Florent-Bechard S, Malaplate-Armand C, Koziel V, et al. Towards a nutritional approach for prevention of Alzheimer’s disease: biochemical and cellular aspects. J. Neurol. Sci. 2007;262:27–36. [PubMed]

2. Söderberg M, Edlund C, Kristensson K, Dallner G. Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids. 2001;26:421–425. [PubMed]

3. Green KN, Martinez-Coria H, Khashwji H, et al. Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-β and tau pathology via a mechanism involving presenilin 1 levels. J. Neurosci.2007;27:4385–4395. [PubMed]

4. Vedin I, Cederholm T, Freund Levi Y, Basun H, Garlind A, Faxen Irving G, Jonhagen ME, Vessby B, Wahlund LO, Palmblad J. Effects of doco- sahexaenoic acid-rich n-3 fatty acid supplementation on cytokine re- lease from blood mononuclear leukocytes: the Omeg AD study. Am J Clin Nutr. 2008;87:1616–22.  [PubMed]

5. Irving GF, Freund-Levi Y, Eriksdotter-Jonhagen M, Basun H, Brismar K, Hjorth E, Palmblad J, Vessby B, Vedin I, Wahlund LO, et al. Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer’s disease: the omega-3 Alzheimer’s disease study. J Am Geriatr Soc. 2009;57:11–  [PubMed]

• 6. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR, Jr., Weiner M, et al. Docosahex- aenoic acid supplementation and cognitive decline in Alzheimer dis- ease: a randomized trial. JAMA. 2010;304:1903–11.

• 7. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen- Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006;63:1402–8. [PubMed]

Websites

Alzheimer Association. Alzheimer’s disease facts and figures. [Accessed 24

Sept. 2015]. www.alz.org/national/documents/report_alzfactsfigures2007.pdf.

Agency for Healthcare Research and Quality. Effects of omega-3 fatty acids on

child and maternal health. Summary (Publication No. 05–E025–1). Evidence

report (Publication No. 05-E025–2) [Accessed 24 Sept. 2015].

www.ahrq.gov/clinic/tp/o3mchtp.htm.

Agency for Healthcare Research and Quality: effects of omega-3 fatty acids on

mental health. Summary (Publication No. 05-E022–1). Evidence

report(Publication No. 05-E022–2) [Accessed 5 Oct 2015]

www.ahrq.gov/clinic/tp/o3menttp.htm.