Wednesday February 3 2016

Mild cognitive impairment can develop into dementia

“How losing weight in middle age ‘could be a sign of dementia’,” the Daily Mail reports. A US study suggests there is an association between middle-age weight change and risk of mild cognitive impairment (MCI) – which, in some cases, can be an early sign of dementia.

Symptoms of MCI include short-term memory loss, problems recalling the right word for something and difficulties with depth perception.

Researchers in the US studied almost 2,000 older adults (aged 70 and over) who didn’t have dementia, and followed them for an average of 4.4 years to see if they developed symptoms of MCI. Medical records were used to establish height and weight measurements from middle age (40 to 65 years old).

Participants who developed MCI in later life experienced greater weight loss per decade in middle age than those who did not – 2kg weight loss compared with 1.2kg respectively. This effect was seen in the group as a whole and separately for men, but not for women. 

The researchers suggest that weight loss may have been due to what is called the “anorexia of ageing”. This is said to be a dysfunction in the production of certain hormones, which then affects dietary intake and metabolism, which could in theory affect risk of MCI and dementia.

There is currently no proven way to prevent MCI or dementia. However, identifying possible markers could help in terms of earlier diagnosis and appropriate care, which could stem brain deterioration and loss of function.

Where did the story come from?

The study was carried out by researchers from the Mayo Clinic and was funded by the National Institutes of Health, the Mayo Foundation for Medical Education and Research, the Robert H. and Clarice Smith and Abigail van Buren Alzheimer’s Disease Research Program, the Clinical and Translational Science Award, and the National Center for Advancing Translational Sciences.

Some of the researchers have worked, or are currently working, for pharmaceutical companies.

The study was published in the peer-reviewed medical journal JAMA Neurology.

This has been reported accurately by the Daily Mail, The Times and The Daily Telegraph, all of which discuss the inherent limitations of the study. The newspapers also provide a number of quotes from the researchers explaining the findings. 

What kind of research was this?

This was a cohort study which aimed to investigate the association between weight change in middle age and risk of MCI in older age. MCI is a prodromal stage (an initial warning sign) before dementia. The researchers report that an estimated 5-15% of people with MCI progress to dementia each year.

The study was prospective in that it recruited a cohort of older adults and then followed them up for cognitive impairment. However, weight change in middle age was collected from medical records through aretrospective study.

Such study designs are good for finding possible links between an exposure and an outcome, which was the aim of this research. However, they cannot prove cause and effect, as various other factors may be involved.

What did the research involve?

Participants were enrolled in the Mayo Clinic Study of Aging. A random sample of residents aged 70 to 89 from a single US county were selected using the medical records linkage system of the Rochester Epidemiology Project. All participants were required to be dementia-free, and must have had at least one follow-up evaluation and data available on maximum weight and height in midlife.

Evaluation of participants was by a nurse or study coordinator using the Clinical Dementia Rating scale and the Functional Activities Questionnaire.

Further cognitive testing was performed using nine tests to assess four domains:

• memory
• executive function
• language
• spatial awareness

Participants were classified as having MCI, dementia or being cognitively normal (if they fell within the normal range and did not meet MCI or dementia criteria). All diagnoses were made by consensus judgement of the nurse or study coordinator, physician and neuropsychologist.

At baseline, demographic variables were recorded, as well as medical history, depressive symptoms, history of cigarette smoking, and current medications (assessed from medication bottles at each evaluation). They also took blood tests to identify people carrying a particular gene (apolipoprotein E ?4 – aka: APOE*E4) that has been linked to the development of Alzheimer’s disease. This was adjusted for in their analyses.

Midlife weight and height was established through medical records.

What were the basic results?

The researchers included 1,895 cognitively normal participants at baseline (average age 78.5 years, 50% male). Over an average period of 4.4 years, 524 participants developed MCI. Those who developed MCI were more likely to be older, have cardiovascular disease, diabetes, and be carrying the APOE*E4 gene. 

A significant difference in average weight change per decade was found between participants who developed MCI and those who did not – a loss of 2.0kg compared to a loss of 1.2kg respectively.

When examining by gender, men who developed MCI had significantly greater weight loss than men who did not (2.1 kg loss vs. 1.2kg loss). For women, there was not much of a difference.

The researchers calculated that a larger weight decline per decade was associated with a 4% increased risk of MCI (hazard ratio 1.04, 95% confidence interval 1.02 to 1.06). This was after adjusting for the possible confounding effects of sex, education, and the presence of the APOE*E4 genotype. Statistical modelling found a weight loss of 5kg per decade to correspond to a 24% increased risk of MCI.

No link with development of dementia was reported.

How did the researchers interpret the results?

The researchers say their findings suggest that increasing weight loss per decade from midlife to late life is a marker for MCI and may help to identify people at increased risk.

Conclusion

This study has investigated the association between weight change in midlife and the risk of MCI in older age.

The study found that participants who developed MCI in later life experienced a slightly greater weight loss per decade in middle age than those who did not. This effect was seen in the group as a whole and for men, but was not significant for women.

The main thing to note is that the researchers are not trying to blame the weight change itself on the increased risk of MCI, just that it could be a marker. The researchers suggest that weight loss may have been due to what is called the “anorexia of ageing”. This is said to be a dysfunction in the production of certain hormones, which then affects dietary intake and energy metabolism, which could in theory affect risk of cognitive impairment and dementia.

However, this theory cannot be proven by this study. The causes of MCI and more serious dementia-related conditions such as Alzheimer’s disease are poorly understood, apart from ageing and possible hereditary factors. This research has taken account of gender, educational status and one gene associated with Alzheimer’s. However, there may be other relevant health and lifestyle factors that are influencing the outcomes seen and have not been accounted for.

Other limitations of the study, which the researchers openly state, are that it is not possible to detect from the records whether the weight loss in middle age was intentional. The study was also conducted in one US region, so may not be generalisable to other populations.

Early symptoms of cognitive impairment or dementia can be mild and progress gradually, which can be difficult to notice. There is currently no proven way to prevent cognitive impairment or dementia. However, identifying possible markers could help in terms of earlier diagnosis and appropriate care, hopefully stemming brain deterioration and loss of function.

If you are worried about memory problems, it’s important to talk to your GP sooner rather than later. Read about the benefits of an early dementia diagnosis.