Shorter Stature Linked to Heightened Dementia Risk

Liam Davenport

November 06, 2014

The risk for dementia-related death is increased in individuals of short physical stature, suggesting that early life circumstances may influence later dementia risk.

A meta-analysis conducted by Tom Russ, MD, PhD, Alzheimer Scotland Dementia Research Centre, University of Edinburgh, United Kingdom, and colleagues showed that dementia-related risk was increased in a dose-dependent fashion relative to decreasing height, with the effect more pronounced in men than women.

"There is good evidence that maximal adult height is linked to a number of early life experiences, including illness, adversity, nutrition, psychosocial stress...and it's quite plausible that these might affect dementia risk," Dr Russ told Medscape Medical News.

"We have been searching for a proxy for something which might capture some of these early life experiences but be feasible to link to dementia, and adult height seems to be quite a useful factor," he added.

Noting the sex difference, Dr Russ told Medscape Medical News: "It does fit with some other findings which suggest that boys are more sensitive to early experiences than girls."

"So the fact that the association is greater in men than women fits with this possibility, given our inference that early life factors are driving the association."

The study was published in the November issue of the British Journal of Psychiatry.

Public Health Implications

According to Dr Russ, there is a "growing body of evidence that dementia is a disorder of the life course."

"It's pretty well accepted that factors in mid-life are associated with dementia risk. We're very interested in early life factors, but there aren't any studies that are sufficiently long where you've got people very well characterized in early life, or even prenatally, with sufficient follow-up for people who go on to develop dementia."

The current study, he added, is part of a much wider effort to identify trigger factors and, ultimately, treatments for dementia, as well as measures that might prevent the devastating disorder.

Data from the Health Survey for England (2004 to 2008) and the Scottish Health Survey (1995, 1998, and 2003), both of which are representative, general population-based samples of UK individuals, were used for 18 independent, cross-sectional studies that had almost identical methodologies and that were conducted on either an annual or occasional basis.

Participants had their height and weight measured by a trained interviewer, and a nurse collected biomedical data. Social class was determined during the interview, along with age in years on leaving full-time education and ethnic class.

Smoking status and the presence of any long-standing illness was also ascertained, and blood pressure was measured. Blood was drawn to determine serum cholesterol levels.

For the analysis, the survey participants were linked to the UK National Health Service death register, for which 88% of individuals had given consent. The number of deaths due to dementia was then assessed.

Complete data were available for 219,624 individuals, 55% of whom were women. The average height of men was 174.4 cm, and that of women was 161.0 cm.

The mean age at baseline was 45.0 years, and the mean age at death among those who died was 55.8 years. Of the 17,553 deaths recorded during a mean follow-up of 9.8 years, 1093 were dementia- related.

The analysis revealed that there was a 26% increase in risk for dementia-related death for each standard deviation (SD) decrease in male height, at a hazard ratio (HR) of 1.26 (P < .001). Among women, the risk for dementia-related death was increased by 10% for each SD decrease in height (HR, 1.10; P = .031).

There was a dose-response relationship between lower physical stature and increased dementia mortality rates, although the association was weaker in women than in men (P = .016 for interaction).

Taking into account numerous variables on multivariate analysis had a minor impact on the association between dementia-related death and SD reduction in height, such that the HR among men was 1.24 (P < .001) and that for women was 1.13 (P < .011).

"There is an awful lot of excellent research which goes on about treating dementia once symptoms have appeared, or slightly earlier than that," Dr Russ commented.

"This is part of a parallel research track looking at prevention to try and see if we can better understand the etiology of dementia, and really try to prevent it from developing in the first instance, rather than trying to minimize the effect once the pathology has already started to accumulate."

"It's a step towards us understanding dementia a little bit better, and there are public health implications because it's showing that early life interventions on a broad spectrum are likely to influence many things, including dementia risk in later life."

Need for More Research

James A. Hendrix, PhD, director, Global Science Initiatives, the Alzheimer's Association, welcomed the study and noted that it points to the need for further studies that will be required to fully understand dementia risk.

"I think that height is a clue for trying to understand dementia risk. It's not really a cause or effect, and I think it speaks to the need for more research," Dr Hendrix told Medscape Medical News.

"[We] have to understand the overall health of people, and I guess that's one of the things that the study authors try to do with looking at blood pressure, cardiovascular and other factors as well," he added.

Dr Hendrix explained that recent studies have indicated that several modifiable risk factors, including exercise and diet and social stimulation, can affect dementia risk, similar to what is seen with heart disease.

"If you can lower your risk by heart healthy activities, you can do the same with Alzheimer's disease," he said, adding: "It could be that early life factors are important too."

Another aspect of early life factors could be the identification of novel therapeutic targets. "The authors mentioned the link to the insulin growth factor IGF-1, which has been implicated in Alzheimer's disease and other dementias. Maybe that's purely speculation on their part but it could...lead us to more research, and we need to support that research with money and funding."

The topic of funding for dementia research has generated a great deal of interest recently, particularly in the United States. "The Alzheimer's Association is a strong advocate for greater research, and we feel that, at least in the US, the current government support of about US$100 million a year is not enough," Dr Hendrix explained.

"We're calling for increased spending with our national plan of US$200 million per year for the funding research to answer questions like how brain development leads to early signs of Alzheimer's disease."

Funding for the study was obtained from the Biotechnology and Biological Sciences Research Council, the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, and the UK Medical Research Council. Dr Russ is employed by the University of Edinburgh and the UK National Health Service and was supported by Alzheimer Scotland during the preparation of this article. Dr Russ is a member of both the Alzheimer Scotland Dementia Research Centre, funded by Alzheimer Scotland, and the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative.

Br J Psychiatry. 2014;205:348–354. Abstract

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