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Fish Oil May Help Keep Brains Sharp and Shapely
Study in seniors links fish oil use to reduced cognitive decline and brain shrinkage
7/24/2014By Craig Weatherby
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Alzheimer’s disease is the most common cause of dementia in people over 65.
It affects about 5.3 million Americans, almost one in two people over the age of 85, and is the sixth leading cause of death.
Unfortunately, the research conducted to date hasn’t revealed any clear ways to prevent or cure this dreaded brain disorder.
So far, the record of research into the ability of dietary omega-3s from fish or supplements to prevent, delay, or diminish dementia has been mixed.
But most studies suggest that diets rich in seafood-source omega-3 fatty acids (DHA and EPA) hold potential to help delay or ameliorate the severity of dementia. (See our sidebar, "Omega-3s vs. dementia: A mixed record”.)
Conversely, poor diets appear to raise the risk of developing Alzheimer's and other forms of dementia … see "Fast Food Diet May Raise Alzheimer’s Risk”.
However, certain gene variations that raise the risk for Alzheimer’s can defy efforts to prevent the disease with diet or treat it with currently approved drugs, which at best are marginally effective.
Indeed, as in prior studies probing the preventive effects of dietary factors – e.g., antioxidants, vitamin D, and omega-3s – genetic variations greatly influenced the outcomes of the study summarized in this article (see our sidebar, "Genetic factors in Alzheimer’s”).
Why would omega-3s help?
Omega-3s come in two basic forms, with distinctly different health impacts:
  • A short-chain omega-3 (ALA) from plant foods
  • Long-chain omega-3s (EPA, DHA, and DPA) from seafood and fish oil
Only omega-3 DHA and EPA are essential to human health and survival.
The body can make DHA from plant-source ALA, though only in very small amounts, and it can make small amounts of EPA from DHA.
Seafood and fish oil (or other "marine” oils like krill oil) are the only abundant sources of both DHA and EPA … which makes them uniquely valuable to optimal human health and child development.
Omega-3 DHA is essential to the human brain and nervous system, constitutes about 15 percent of the brain’s fatty acids, and plays critical structural and functional roles.
For example, DHA regulates the expression of key "working” genes in the brain, and it both stimulates and enables growth of the branching structures (dendrites and axons) that extend from brain cells (neurons) and connect them to each other.
Genetic factors in Alzheimer’s
The APOE gene comes in several different forms, or alleles, three of which – APOE2, APOE3, and APOE4 – occur most often.
People who develop Alzheimer's are more likely to have an APOE4 allele than people who do not develop the disease.
APOE4 is present in about 25 to 30 percent of all people, and in about 40 percent of people with late-onset Alzheimer's.
People who inherit one or two APOE4 alleles also tend to develop the disease at an earlier age than those who do not have any APOE4 alleles.
Carriers of two E4 alleles have between 10 and 30 times the risk of developing AD by 75 years of age, compared to those not carrying any E4 alleles.
Why would the APOE variant matter?
Alzheimer’s disease is characterized by – though not necessarily caused by – build-up of beta-amyloid protein plaque and tau protein tangles in the brain.
And some evidence suggests that people with APOE4 alleles are not as efficient at removing amyloid plaque.
Critically, omega-3 EPA and DHA moderate inflammation, which is known to promote and worsen Alzheimer's and other forms of dementia.
And some studies indicate that these seafood-source fats might exert unique effects, while a shortage of omega-3s may both exacerbate dementia and be caused by it: see "Omega-3s May Purge Alzheimer's Plaque” and "Alzheimer's Patients Can't Make Brainy Omega-3”.
Fish oil appeared to help keep brains sharp and shapely
The new findings come from Rhode Island based researchers participating in the worldwide Alzheimer’s Disease Neuroimaging Initiative (Daiello LA et al. 2014).
Their study involved 819 people aged 55 to 90 years:
  • 229 cognitively normal seniors (NC)
  • 397 with mild cognitive impairment (MCI)
  • 193 patients with Alzheimer's disease (AD)
Each volunteers’ brain performance and structures was measured with neuropsychological tests and magnetic resonance imaging (MRI) scans every 6 months.
The NC and MCI groups were followed and tested for up to four years, while the participants with Alzheimer's disease were tested at 6-month intervals for up to two years, and again after three years.
To see if fish oil might help, the scientists compared the results of the brain tests and scans of the 117 participants who reported regular consumption of fish oil to the results of the 682 who did not take fish oil.

And the results suggest that fish oil supplements may do three good things in older adults:
  • Reduce age-related cognitive decline (senility)
  • Prevent brain atrophy (a risk factor for Alzheimer’s)
  • Prevent or delay the onset of the development of Alzheimer’s disease in people free from a key genetic risk factor (APOE4).
The volunteers who reported taking fish oil supplements during the study had lower (better) scores on a test for the Alzheimer's disease symptoms and those without Alzheimer's disease had higher (better) scores on a test of brain performance.
Taking fish oil supplement was also linked to less atrophy – loss of gray matter – in the brain regions associated with thinking (cerebral cortex) and memory (hippocampus).
Importantly, the apparent benefits of taking fish oil were only found in those without the gene variation (APOE E4) proven to greatly raises the risk of Alzheimer’s disease.
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  • Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010 Nov 3;304(17):1903-11. doi: 10.1001/jama.2010.1510.
  • Song X, Mitnitski A, Zhang N, Chen W, Rockwood K; Alzheimer's Disease Neuroimaging Initiative. Dynamics of brain structure and cognitive function in the Alzheimer's disease neuroimaging initiative. J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):71-8. doi: 10.1136/jnnp-2012-303579. Epub 2012 Nov 2.
  • Trzepacz PT, Yu P, Bhamidipati PK, Willis B, Forrester T, Tabas L, Schwarz AJ, Saykin AJ; Alzheimer's Disease Neuroimaging Initiative. Frontolimbic atrophy is associated with agitation and aggression in mild cognitive impairment and Alzheimer's disease. Alzheimers Dement. 2013 Oct;9(5 Suppl):S95-S104.e1. doi: 10.1016/j.jalz.2012.10.005. Epub 2012 Dec 17.
  • Vemuri P, Weigand SD, Przybelski SA, Knopman DS, Smith GE, Trojanowski JQ, Shaw LM, Decarli CS, Carmichael O, Bernstein MA, Aisen PS, Weiner M, Petersen RC, Jack CR Jr; Alzheimer's Disease Neuroimaging Initiative. Cognitive reserve and Alzheimer's disease biomarkers are independent determinants of cognition. Brain. 2011 May;134(Pt 5):1479-92. doi: 10.1093/brain/awr049. Epub 2011 Apr 7.
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