In the ever-evolving saga about body weight and dementia, the plot just thickened. In fact, it put on some serious poundage. According to the largest study ever conducted on the subject, obese people in the United Kingdom carried a third lower risk of developing dementia than healthy-weight peers, while their underweight compatriots padded their risk by the same amount. The study stands against a backdrop of conflicting evidence—some previous studies linked mid-life obesity to dementia; others did not. The findings underscore the complex relationships between dementia and lifestyle factors, such as body weight. Researchers led by Stuart Pocock at the London School of Hygiene and Tropical Medicine reported their findings in the April 10 Lancet Diabetes and Endocrinology,
Before you inhale that entire tub of ice cream, know that the other health risks of obesity still outweigh the benefits of potentially dodging Alzheimer’s and similar diseases. “Even if obesity protects you from developing dementia, you may not live long enough to get the benefit,” cautioned first author Nawab Qizilbash of OXON Epidemiology, a contract research organization in Madrid. Shorter life expectancy did not explain why people with high body-mass index were spared from dementia, however, because Qizilbash and colleagues corrected for a host of potentially confounding factors including mortality.
Research conducted in the last decade paints a murky picture of the body weight/dementia dynamic. Epidemiological data from several countries indicates that obesity in middle age increases the risk of dementia later in life (see Kivipelto et al., 2005; Xu et al., 2011; Chiang et al., 2007). Typifying the “obesity paradox,” other findings suggested that while middle-age obesity raises the later risk of dementia, obesity in old age actually protects people (see Fitzpatrick et al., 2009). Others found that being underweight can precipitate dementia, while being overweight protects (see Strand et al., 2013; Stewart et al., 2005). Some studies found that the girth of the midsection, but not body mass index, elevated dementia risk (see Whitmer et al., 2008; Gustafson et al., 2009). Overall, a meta-analysis on Alzrisk indicated that being over- or underweight may be a risk factor for dementia at some point in life, but that more studies with longer follow-up times were needed.
Qizilbash and colleagues drew from the United Kingdom Clinical Practice Research Datalink. CPRD is a massive database containing health information about anyone in the country who has visited a general practitioner. They looked at the earliest available BMI measurement for nearly 2 million people who were 40 years old or older between 1992 and 2007, and retrospectively tracked the cohort for dementia diagnoses until 2013. They then compared dementia rates with those one-time baseline BMI measurements.
During an average of more than nine years of follow-up, a dementia diagnosis was made in 45,507 people, or 2.4 percent of the cohort. Compared to people who had a healthy BMI of 20-24.9, those whose BMI was lower had a 34 percent higher incidence of dementia. In contrast, dementia incidence went down as BMI rose above 25, with very obese people with a BMI over 40 having a 29 percent lower risk of developing dementia than healthy-weight people. These associations held up when the researchers adjusted the data for age, smoking, alcohol use, diabetes, previous heart attack, and the use of statins or anti-hypertensive drugs.
The correlations held up regardless of how long people were tracked after their baseline BMI measurement. In other words, underweight people had the highest risk of dementia of all BMI groups at one year or 15 years after their BMI measurement. Obese people in the study were younger, on average, at baseline than those who were underweight, but that did not explain why they were protected—the relationships between BMI and dementia held steady even when the researchers considered only people whose initial BMI measurement was taken by age 55.
To address the obvious question of whether obese people escaped dementia by dying earlier, the researchers adjusted for mortality. They found that while body weight associated with mortality (both obese and underweight people had higher death rates than healthy-weight people), adjusting for that did not dramatically alter the association with dementia. Even when taking each person who died and counting him or her as a survivor who was twice as likely to develop dementia because of some ongoing co-morbidity, obese people still had a 20 percent lower risk of developing dementia than healthy-weight people.
Deborah Barnes of the University of California, San Francisco, was impressed by the study’s size and extensive controls. “This is a really interesting study that calls into question the belief that obesity in mid-life is associated with an increased risk of developing dementia later in life,” she wrote. “It still is not clear whether this is a causal relationship or whether BMI is a marker of something else—perhaps socioeconomic status or access to enough food.”
Researchers were hesitant to speculate why obesity would protect against dementia. Costantino Iadecola of Weill Cornell Medical College in New York offered that increases in adipocyte hormones such as leptin might be involved because they are thought to be neuroprotective. However, he noted that the protective effect of being overweight flattened out as BMI increased in the study, suggesting that a simple linear relationship between leptin and reduced dementia risk was unlikely.
Iadecola cautioned against over-interpretation of the results, pointing out that BMI is not a measurement of overall health, and does not explain why a person is over- or underweight. “Someone’s body weight is a result of myriad different influences that you cannot just sum up with one number,” he said. Iadecola said that, for example, the location of fat tissue in the body influences its health effects. Also, people who are underweight could have lost fat, muscle, or bone, all of which influence health outcomes differently. He added that food intake should not be interpreted as the only factor influencing weight loss or gain, as metabolic conditions can play a role. Finally, Iadecola noted that different forms of dementia are likely to be influenced by different health and cardiovascular factors, and the study did not distinguish between dementia types.
“This provocative study brings to the forefront our need to gain an understanding of how body weight is regulated in different age groups, and its cognitive impact,” he said. “We have to use this as a starting point.”
Because this study was based on a baseline measure of BMI, Qizilbash said the researchers will next consider how gaining or losing weight affects dementia. For example, dementia risk could be different for a person who has been underweight all of his or her life than another person who rapidly starts shedding pounds due to a health problem. Qizilbash said the most important finding of his study is that being underweight is a strong risk factor for dementia, even many years prior to onset. “This risk factor needs to be addressed,” he said. Regarding the obesity side of the data, Qizilbash said, “The idea that reduction in obesity will lead to a reduction in dementia is probably incorrect.”
In an accompanying commentary, Deborah Gustafson of the University of Gothenberg in Sweden struck a cautious tone. She mentioned several limitations, including the lack of specific dementia diagnoses and the wide distribution of age at which BMI was measured in the cohort. “To understand the association between BMI and late-onset dementia should sober us as to the complexity of identifying risk and protective factors for dementia,” she wrote. “The report by Qizilbash and colleagues is not the final word on this controversial topic.”—Jessica Shugart
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No Available Further Reading
- Qizilbash N, Gregson J, Johnson ME, Pearce N, Douglas I, Wing K, Evans SJ, Pocock SJ. BMI and risk of dementia in two million people over two decades: a retrospective cohort study. Lancet Diabetes Endocrinol. 2015 Jun;3(6):431-6. Epub 2015 Apr 9 PubMed.