Can limb length affect dementia risk?

“Longer limbs 'mean less risk of dementia'” reads the headline in The Guardian today. It goes on to report that a study in the US followed 2,798 people, with an average age of 72, over a period of five years. It found that women who had longer legs and arms were less likely to develop dementia, while the women “with the shortest arms were 50% more likely to develop the disease than those with the longest arms”. In men, the only significant association found was between arm length and risk of Alzheimer's disease, “with every extra inch lowering their risk by 6%”. The newspaper reports that the researchers believe that this may be explained by people with shorter limbs having had poorer nutrition in early life.

Although the study on which this story is based was relatively well conducted, we cannot be certain that these results reflect a true association between limb length and dementia, or that this association is due to nutrition as a child. Good nutrition is important at all stages in life because it has many health benefits and it would be surprising if this did not include cognitive benefits.

Where did the story come from?

Dr Tina Huang and colleagues from the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and other universities in the US carried out this research. The study was funded by the National Heart, Lung, and Blood Institute, and grant AG15928 from the National Institute on Aging. It was published in Neurology , a peer-reviewed medical journal.

What kind of scientific study was this?

This study was part of the large prospective cohort study, the Cardiovascular Health Study (CHS), which enrolled 5,888 people in four American states between 1989 and 1993 and followed them up until 1999. The current part of the study (the CHS cognition study) began in 1992–1993 and used a subgroup of the participants enrolled in the CHS. The study looked at whether limb length, which may reflect the quality of nutrition and other environmental factors which a person is exposed to in early life, was related to a person’s risk of developing dementia.

The subgroup included 3,608 CHS participants who had MRI brain scans and underwent standard cognitive testing with the Mini-Mental State Examination in 1992–1993. All CHS participants had their knee height (from the ground) measured in 1989–1990, and their arm span measured in 1996–1997. The participants were assessed annually and this assessment included standard tests of cognitive function. Participants also had an additional MRI in 1997–1998.

In 1998–1999, all the participants who were considered to be at high risk of having dementia (based on the results of the cognitive tests and medical records), as well as all ethnic minority participants, those who had had a stroke and those in nursing homes underwent further neuropsychological testing either at home or in a specialist clinic. If a participant had died or refused further testing, then their medical records and cognitive test results were supplemented by interviews with their physician and other informants.

All participants at one study site (regardless of whether they were at high risk of dementia or not) had further neuropsychological testing to determine whether the screening method used in the study would have found all people with dementia. A panel of experts (neurologists and psychiatrists) used all of the information collected to work out whether or not each participant had dementia, based on roughly accepted criteria. The type of dementia a person had was also defined, based on accepted criteria and MRI results. People who provided insufficient information or who were judged to have had either dementia or mild cognitive dementia when they enrolled were excluded from analyses: this left 2,798 participants.

The researchers used statistical methods to look at whether a participant’s knee height or arm span was related to their risk of dementia. The researchers conducted separate analyses for men and women. These analyses were adjusted for factors known to be related to risk of dementia or to limb length, including age, race, education, income, whether they had a particular form of the APOE gene (the APOE ε4 allele) that increases risk of dementia, and self-reported health.

What were the results of the study?

The average age of people in the study was 72, and they were followed up for 5.4 years on average. People’s knee height and arm span reduced with increasing age. However, knee height and arm span increased with increasing years in education. It was also increased in black people and in women without an APOE ε4 allele and women with higher incomes.

As women’s knee height and arm span increased, their risk of developing dementia and Alzheimer’s disease decreased. Women with arm spans in the lowest 20% of measurements were about one and a half times more likely to develop dementia and Alzheimer’s disease than other women. Men who had wider arm span were less likely to develop dementia and Alzheimer’s disease, but this was only just statistically significant. There was no relationship between men’s knee height and risk of dementia.

Neither knee height nor arm span in men or women showed statistically significant associations with the risk of vascular dementia.

What interpretations did the researchers draw from these results?

The researchers concluded that “early life environment may play an important role” in the risk of developing dementia later on in life.

What does the NHS Knowledge Service make of this study?

This study was relatively large and did use data that was collected prospectively. However, it does have some limitations:

• The differences in dementia risk with different limb lengths was only observed if limb length was analysed in one particular way (as a continuous spectrum) and not another (comparing dementia risk above and below a particular limb length).
• As with all studies of this type, where the groups being compared cannot be randomly assigned, there will be imbalances between the characteristics of the groups. Although the researchers tried to take into account known differences between people with different limb lengths in their analyses, these adjustments may not have fully removed the effects of these known factors and could not remove the effects of unknown factors.
• Not all participants received full neuropsychological testing and this may mean that some cases of dementia may have been missed. Testing of all the people from one study centre found that the screening process did miss some people with dementia.
• A diagnosis of Alzheimer’s disease can only be confirmed by an autopsy, therefore there may have been some misclassification of diagnoses and this might have affected the results. 
• Data on arm span was missing for about a quarter of participants and inclusion of this data may have affected results.
• This study was carried out in the US and in a largely white population, therefore it may not apply to other countries or populations with different ethnic backgrounds. In addition, the elderly people included in this study will have had very different environments and nutrition to that of children today. Therefore, these results may not apply to people born at later times.
• The authors note that, ideally, measurements of limb length should have been taken earlier in life, as the initial stages of the cognitive decline seen with dementia could already have started by the time these measurements were taken.

Although limb length was used as an indicator of childhood nutrition, it is not possible to state with certainty from the study that the association seen is due to nutrition as a child. However, good nutrition is important at all stages in life because it has many health benefits and it would be surprising if this did not include cognitive benefits.

Sir Muir Gray adds...

The fact that that two things are associated with one another statistically does not mean that one causes the other.