High Omega-3 Status reduces brain white matter lesions associated with Cognitive Decline 1.

 

A new study has shown that higher blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are  associated with less executive decline over time and better executive function that corresponds with fewer age-related lesions in white matter of the brain1.  The collaboration between the Brain Institute, Oregon Health and Science University, Portland, Oregon and the Beckman Institute for Advanced Science and Technology , Urbana, Illinois, USA, included 86 non-demented adults aged 65 years and older from the Oregon Brain Aging Study who gave a blood sample at the start of the study and were tested annually for the next 4 years for brain function using various tests and for the development of brain lesions by MRI scan.  Every increase in EPA+DHA concentration by 100 μg/ml resulted in a 1 year delay in age-dependent executive decline irrespective of age, gender, education, genetic predisposition, hypertension or depression. Blood EPA + DHA concentrations above 110 μg/ml were associated with more stable executive function over time suggesting this could be the minimum threshold for neuroprotection.

 

An earlier study including 2313 people aged >/= 65 years reported a 40% lower risk of minor stroke and a 42% lower risk of changes in brain white matter over five years in people who have high blood levels of omega-3 long chain polyunsaturated fatty acids (LC-PUFAs) derived from fish2.  This protection was only attributable to DHA and not to any other omega-3 fatty acid.  including alpha-linolenic acid (ALA). All of these changes were independent of age, sex, race, education, diabetes, coronary heart disease, hypertension, alcohol intake, smoking, or use of aspirin, lipid-lowering or hypertension medications.

 

Previous population studies have consistently shown that EPA+DHA intake reduces mild cognitive impairment (MCI). In 2007, one study reported those who ate 10 grams or more of fish or fish products per day had significantly better test scores and a lower prevalence of poor cognitive performance than did those whose intake was less than 10 g/day3.  The second study showed that those with higher blood levels of EPA and DHA had less decline in sensorimotor speed and complex speed over three years4.  Two additional studies showed that men who ate about 400 mg of omega-3 LC-PUFAs per day had less cognitive decline in a five year period than those who ate only about 20 mg/day5 and that higher blood levels of EPA+DHA prevented deterioration in verbal fluency6.  In November 2006, the Framingham Heart Study which followed 899 initially healthy volunteers with a median age of 76 years7 showed that people who ate two or more servings of fish per week were 39 percent less likely to develop dementia, but those who ate less than that did not derive any benefit. Although oily fish contains both EPA and DHA, it was only the DHA that was responsible for preventing dementia in this study.  A 2013 UK study showed that brain function in the aged becomes worse as their dietary intake and blood levels of omega-3 LC-PUFAs decreases8.

 

Randomized, double-blind, placebo controlled clinical studies measuring brain function in MCI have reported  improvements in learning and memory skills the equivalent of a person three years younger in older adults taking 900 mg/day of DHA9,  no decline in cognitive function following either placebo or EPA+DHA treatment in healthy adults aged 70-79 years 10 and improvements in cognitive test scores in the active as well as the placebo group mostly due to learning effects in cognitively healthy adults11.  The improvements measured in the placebo group masked the effects of the active and the researchers stated that the choice of placebo may not have been appropriate.  Following that, a trial including 50 people aged >65 years with MCI allocated to receive an EPA rich supplement, a DHA rich supplement, or a placebo showed enhanced verbal fluency after six months of treatment12.

 

Most recently, a randomised, double-blind, placebo-controlled trial reported significant improvements in short-term and working memory, immediate verbal memory and delayed recall capability following treatment with 1.3 g DHA + 0.45 mg EPA daily for 12 months13.  This trial was the first study specifically designed to measure cognitive improvements (rather than prevention of decline) in people with MCI associated with age. The DHA rich oil was well tolerated and the side effects were minimum and self-limiting with the main complaints being difficulty swallowing the capsules, constipation and mild gastrointestinal discomfort equally distributed amongst the DHA and placebo group.

 

This latest study showed that executive decline with age may be particularly sensitive to omega-3 LC-PUFA status and that these nutrients may protect executive function partly by preventing the formation of white matter lesions in the brain. Combined, the strength of these studies demonstrates that value of DHA rich supplements to safely reduce incidence and severity of MCI and to enhance cognitive performance in those with MCI.

 

References:

1.             Bowman GL, Dodge HH, Mattek N, Barbey AK, Silbert LC, Shinto L, Howieson DB, Kaye JA, Quinn JF.  Plasma omega-3    PUFA and white matter mediated executive decline in older adults. Front Aging Neurosci. 2013 Dec 16;5:92. doi:        10.3389/fnagi.2013.00092.

2.             Virtanen JK, Siscovick DS, Lemaitre RN et al. Circulating Omega-3 polyunsaturated fatty acids and subclinical brain               abnormalities           on MRI in older adults: The Cardiovascular Health Study. Journal of the American Heart Association doi:    10.1161/JAHA.113.000305.

3.             Nurk E, Drevon C, Refsum H, Solvoll K, Vollset S, Nygård O, Nygaard H, Engedal K, Tell G, Smith D. Cognitive performance among   the elderly and dietary fish intake: the Hordaland Health Study. Am J Clin Nutr  2007;86:1470-8.

4.             Dullemeijer C, Durga J, Brouwer I, Van de Rest O, Kok F, Brummer R-J, Van Boxtel M, Verhoef P.  N-3 fatty        acid proportions in plasma       and cognitive performance in older adults. Am J Clin Nutr 2007;86:1479-85.

5.             van Gelder BM, Tijhuis M, Kalmijn S, Kromhout D. Fish consumption, n-3 fatty acids and subsequent 5 year          cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr 2007 Apr;85(4):1142-7.

6.             Beydoun MA, Kaufman JS, Satia JA, Rosamond W, Folsom AR. Plasma n-3 fatty acids and the risk of cognitive decline in older adults:                 the Atherosclerosis Risk in Communities Study. Am J Clin Nutr 2007 Apr;85(4):1103-11.

7.             Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins S et al. The Framingham Heart Study. Plasma Phosphatidylcholine                 docosahexaenoic acid content and risk of dementia and Alzheimer Disease. Arch Neurol. 2006;63:1545-1550.

8.             Phillips MA, Childs CE, Calder PC, Rogers PJ. Lower omega-3 fatty acid intake and  status are associated with poorer cognitive function              in older age: a comparison of  individuals with and without cognitive impairment and Alzheimer’s disease. Nutritional                                                Neuroscience 2012;15(6):271-277.

9.             Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M, on behalf         of the MIDAS          Investigators. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 2010 Apr 29    doi:10.1016/j.jalz.2010.01.013

10.           Dangour AD, Allen E, Elbourne D, Fasey N, Fletcher A, Hardy P, et al. Effect of 2 year n-3 long chain polyunsaturated fatty acid                 supplementation on cognitive function in older people (the OPAL study): a            randomized, double-blind, controlled trial. Am J Clin Nutr                 2010;91:1-8.

11.           Van de Rest O, Geleijnse JM, Dullemeijer C, OldeRikkert MGM, Beekman ATF, DeGroot CPGM. Effect of fish oil on cognitive            performance in older subjects. Neurology 2008;71:430-438.#

12.           Sinn N, Milte CM, Street SJ, Buckley JD, Coates AM, Petkov J, Howe PR. Effects of n-3 fatty acids, EPA v. DHA, on depressive         symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised            controlled trial. Br J Nutr. 2012 Jun;107(11):1682-93. doi: 10.1017/S0007114511004788. Epub 2011 Sep 20.

13.           Lee LK, Shahar S, Chin AV, Yusoff NA. Docosahexaenoic acid-concentrated fish oil supplementation in subjects with mild cognitive    impairment (MCI): a 12-  month randomised, double-blind, placebo-controlled trial. Psychopharmacology 2013;225:605-612.