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Alzheimer’s and intelligence

Monday 7 April 2008

“Fish oil brain boost,” is the headline in the Daily Mail today. The paper says that a “breakthrough in the battle against Alzheimer's is being claimed by British scientists who believe it can be fought with omega-3 oils”. The newspaper adds that “older people whose diets are rich in omega-3 oils do better in mental tests than those without the oils in their diets”.

The story is based on a study that investigated people aged about 66 to 68 years who had taken an intelligence test at school when they were 11. The researchers looked at whether there was any link between the fatty-acid content of some of these people’s red blood cells and their performance in that intelligence test and in later assessments of cognition. The study was not set up to establish whether there was any effect of dietary fatty acids on improved intelligence or brain activity. The only way to address this particular question is through further randomised controlled trials.

Where did the story come from?

Dr Lawrence Whalley and colleagues from the University of Aberdeen, the University of Edinburgh, Robert Gordon University, the University of Dundee and the Rowett Research Institutes carried out this research. The study was funded by the Wellcome Trust and the Alzheimer’s Research Trust. It was published in the American Journal of Clinical Nutrition , a peer-reviewed medical journal.

What kind of scientific study was this?

The study was a retrospective cohort study of Scottish people who had taken an intelligence test called the Moray House Test at school in 1947 when they were 10 to 11 years old. Those people who were still alive and were living independently in the community in good general health between November 1999 and February 2002 were identified from local health registers. They were then invited to participate in this follow-up study. Of the original 660 people who were invited to take part, 506 (76%) agreed to, and data was available for 478 participants. These people were interviewed and demographic and dietary information (including the use of fish-oil supplements) was recorded. The participants were invited for further assessment when they were aged between 66 and 68 years old (i.e. about two years later); overall, 289 people participated in all three assessments.

At each follow up assessment, cognitive testing was performed (to screen for dementia), as well as tests of verbal memory and non-verbal reasoning as well as executive function, psychomotor performance and constructional ability. Blood was taken and the DNA was analysed  to determine whether a gene that is known to increase susceptibility to Alzheimer’s – _APOE _ ε4 – was present.

The fatty acid content of blood cells (n-3 PUFA – a type of fatty acid found in fish oils) was measured in a subgroup of participants (120 people, equal numbers of fish-oil supplement users and non-users). The researchers looked at whether there was an association between the n-3 PUFA content of cells and ability at both 11 years old and at 63 to 65 years. They also looked at whether carrying the _APOE _ ε4 gene had any effect on the relationship between the level of fatty acids in the cells and general ability. Genetic data was only available for 113 people.

What were the results of the study?

The researchers found that in people who were carrying the gene variant APOE ε4, total fatty acid concentrations were not linked to general intelligence at age 11 or at age 64 years. In people who did not have the _APOE _ ε4 gene, the high total fatty acid content and “intelligence” at age 11 and 63–65 were significantly linked. When they analysed the components of ‘total’ fatty acid separately, they found that both n-3 PUFA and DHA (another fatty acid which is found in fish oils) were significantly associated with higher scores. However, the link with DHA was no longer significant when researchers took into account other factors that might be responsible such as gender and gene variant status.

What interpretations did the researchers draw from these results?

The researchers conclude that cognitive testing at age 11 and at follow up were linked to total fatty acid content in the cells (of n-3 PUFA and DHA – both of which can come from fish oils).

What does the NHS Knowledge Service make of this study?

It is difficult to interpret this study. There are several points to keep in mind:

  • The researchers say that people with better functioning are more likely to have stayed in the study. This would mean that the people available for analysis at the end of the study aren’t truly balanced and don’t represent the distribution of characteristics in the starting population. The researchers believe this didn’t have much of an effect on their results. For measures of fatty acid, this imbalance may have less of an effect because their sample for this aspect of the testing was not random (i.e. they selected equal numbers of people who took fish oil supplements and those who didn’t).
  • The researchers found a link between cognitive benefits and the concentration of the fatty acid n-3 PUFA in the red blood cells only in the absence of a gene variant that is associated with increased risk of Alzheimer’s disease (_APOE _ ε4). The researchers put forward some theories for why this might be the case, all of which need to be assessed in further studies. The researchers acknowledge that as they only had genetic data from 38 carriers of this gene variant, their study is not large enough to detect any real differences if they are there. This again suggests that more research is needed to clarify this issue.
  • Importantly, though the researchers say that they collected information on diet, they do not set out to establish any link between consumption of fish oils or any element of diet and cognitive performance or intelligence. Their focus is on the link between the content of fatty acids in red blood cells and these outcomes. Although other studies may explore the relationship between fish oil intake and the concentration of these fats in the cells, this one did not. In fact, in their discussion, the researchers state clearly that though the association they found between better cognitive performance in later midlife and higher concentration of fatty acids in red blood cells may be explained by “a life-long healthier lifestyle that includes a diet rich in marine oils or supplementation with n-3 PUFAs and many other micronutrients, or both”. Though they conclude that this seems an unlikely explanation of the results reported here, it isn’t clear whether this is a valid explanation. 
  • When assessing “cognitive benefits”, the researchers combined the results from all six tests they performed during the follow ups. The appropriateness of assuming that a single “general cognitive trait” (common to each of the tests) was being measured and combining all these test results into a single representative score is unclear.

Overall, this study provides some evidence of an interaction between a gene and the environment that affects cognition during advancing age. It isn’t clear how the study’s weaknesses should affect the interpretation of the results, but perhaps the most important point is that this study was not looking directly on the effect that dietary fish oils could have on cognition.

Sir Muir Gray adds...

I don’t think that I will increase my intake of oil based on this evidence.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Fish oil brain boost.

Daily Mail, 7 April 2008

Fish oils offer Alzheimer's disease hope.

The Scotsman, 7 April 2008

Links to the science

Lim WS, Gammack JK, Van Niekerk JK, Dangour AD.

Omega 3 fatty acid for the prevention of dementia.

Cochrane Database Syst Rev 2006, Issue 1

Whalley LJ, Deary IJ, Starr JM, et al.

n–3 Fatty acid erythrocyte membrane content, APOE ε4, and cognitive variation: an observational follow-up study in late adulthood.

Am J Clinical Nutrition 2008; 87:449-454