Prevention of age-related cognitive decline - a public health challenge.Nutrition, a major lifelong environmental factor, offers promising perspectives.

1. OMEGA 3
FAs in the
ALZHEIMER’S DISEASE
(HFN- 690)
Maibam Baby Devi
I.D No. 48048
M.Sc Foods & Nutrition
2nd Year

2. Overview
 Introduction to alzheimer’s disease
Causes & symptoms
Omega 3 fatty acids
Functions
Mechanism of action
Omega 3 and alzheime’rs disease trials
Summary
Future research
Bibliographies

3. 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

5.  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.

6. 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.

7. GLOBAL PREVELANCE

8.  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

9. 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

10. 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.

11. 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

13. Modifiable factors
 Vascular Disease
Hypertension
 Diabetes
 Dyslipidaemia
 Stress
 Diet
Non modifiable
factors
Age
Family history
 ApoE4 gene.
Depression
 Head trauma
 Mutation

14. 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.

15. 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.

16.  “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.

18. 1. Preclinical
2. Mild cognitive impairment
3. Dementia.
• deficits in spatial cognition,
impaired face recognition.
• impaired reasoning, judgment, and
problem solving.
THE MAIN SYMPTOMS

19. Early Onset Alzheimer’s
 Between the ages of 30 and 60 years
 Young-onset, accounting 5%
 Mutations in APP, PS1, and PS2.

20.  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

21.  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

22. STRUCTURE
 Alpha-linolenic
acid (ALA)
 Eicosapentaenoic
acid (EPA)
 Docosahexaenoic
acid (DHA)
Omega 3 fatty acids

23. SOURCES
ALA
• Flaxseed 18.1%
• Hempseed 8.7%
• Butterfruits- 8.7%
• walnuts- 6.3%
• Hazel nuts -0.1%

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

25.  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

26. Disease Prevention:
 Impaired Visual and
Neural Development
 Coronary Heart Disease
 Sudden Cardiac Death
 Cancer
 Diabetes Mellitus
 Inflammatory Diseases
Rheumatoid arthritis
 Inflammatory Bowel Disease
Ulcerative colitis and Crohn’s
Disease
 Asthma
 Depression & Bipolar Disorder
 Schizophrenia

27.  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

28.  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.

29.  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

30.  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….

31.  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

33. 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

34. 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

35. Omega-3 fatty acids do not interact with most other
medications.
Increased risk of bleeding eg;
hemophilia
Stomach upset,
 change in the bowel movements

36. JOIN ALZHEIMER’S DISEAE
RESEARCH

37. RESEARCH
Study Omega 3 Fatty
Acids Amounts
Findings
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

38. 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

39. 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.

40.  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.

41. 1. Florent-Bechard S, Malaplate-Armand C, Koziel V, et al. Towards a
nutritional approach for prevention of Alzheimer’s disease: biochemical
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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]

42. 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]

43. 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.