Medscape.com
Deborah Brauser
August 21, 2014

Midlife obesity is linked to an increased risk for later-life dementia, but the strength of that association may vary according to an individual’s age, new research suggests.

A retrospective cohort study of more than 450,000 obese individuals in England showed that those who were first hospitalized for obesity in their 30s were 3 times more likely to go on to develop dementia than their healthy peers.

The risk dropped to a 1.7 risk ratio (RR) for dementia in participants who were between 40 and 49 years of age when first diagnosed with obesity. However, obesity in those older than 79 years appeared to be protective, inasmuch as those individuals were 22% less likely to develop subsequent dementia.

“Ours is an epidemiological study, done without the expectation that we would find new knowledge of direct clinical relevance,” principal investigator Michael J. Goldacre, professor of public health in the Nuffield Department of Population Health at the University of Oxford, United Kingdom, told Medscape Medical News.

“But if the findings in the young are cause and effect ― that obesity contributes to the development of dementia, either directly or via its association with a raised risk of circulatory disease ― dementia becomes yet another hazard of obesity. So, if cause and effect, the findings add to the importance of dealing with the obesity epidemic,” he added.

The study was published online August 20 in the Postgraduate Medical Journal.

Youngest at Highest Risk

The investigators examined hospital care and mortality records from 1999 to 2011 for 451,232 people in England older than 29 years who were obese (57% women). Each person’s first recorded episode of hospital day care or admission due to obesity was entered into the analysis.

A matching number of individuals acting as the “healthy controls group” was identified from admission records for relatively minor medical and surgical conditions and injuries.

Results showed that the subgroup hospitalized for obesity between the ages of 30 and 39 years had a 3.5 RR for dementia (95% confidence interval [CI], 2.1 – 5.6; P < .001) vs their age-matched counterparts who were not obese. Compared with their nonobese age-matched peers, the subgroup that first showed a recording of obesity between the ages of 40 and 49 years had an RR of 1.7 (95% CI, 1.3 - 2.2), those between 50 and 59 had an RR of 1.5 (95% CI, 1.3 - 1.7), and those between 60 and 69 had an RR of 1.4 (95% CI, 1.3 - 1.5; all, P < .001). Interestingly, those diagnosed with obesity in their 70s "had neither an increased nor a reduced risk of subsequent dementia" (RR, 0.97; 95% CI, 0.93 - 1.01), report the investigators. Also interesting, those 80 and older at first diagnosis of obesity had a reduced risk of developing dementia (RR, 0.78; 95% CI, 0.74 - 0.82). Differences between men and women did not significantly change any of the associations. AD and Vascular Dementia

Subanalysis showed that 940 of the obesity group members had Alzheimer’s disease (AD), and 1716 had been diagnosed with vascular dementia. There was an RR of 5.4 for AD in those who were aged 30 to 30 years at first record of obesity (95% CI, 1.7 – 13.7; P = .001) and an RR of 5.6 (95% CI, 1.0 – 19.5; P = .02) for vascular dementia in the same age group.

The patients who had a first record of obesity at 40 to 49 years, 50 to 59 years, and 60 to 69 years had significantly increased risks for vascular dementia (RR, 2.8, 2.5 and 1.9, respectively).

In the older groups, risk for vascular dementia was not significant for those with obesity who were between the ages of 70 and 79 and decreased in those who were 80 years and older (RR, 0.8). Risk for AD decreased steadily for those with obesity in their 60s (RR, 0.82), 70s (RR, 0.60), and 80s (RR, 0.51).

“The risk of dementia was highest in people with a record of obesity when aged 30-39 years and the level of risk reduced in a graded way…with increasing age,” write the investigators.

However, “an increased risk associated with mid-life obesity may be specific to vascular dementia,” they add.

Dr. Goldacre noted that the agreement between their results and those found in other recent studies “adds confidence that the findings are real.”

“The association between obesity and an elevated risk of dementia, in youngish people at least, is perhaps no great surprise. Obesity is associated with an elevated risk of circulatory disease; circulatory disease is associated with an elevated risk of vascular dementia,” he said.

What was a bit more surprising was that obesity might actually be protective against dementia in the elderly, added Dr. Goldacre.

“One possible explanation is simply that obese people who are not prone to obesity-related premature death, the ‘survivors,’ are indeed not at risk in old age. Another possibility is that, in people whose obesity may have genetic determinants, obesity may have certain survival benefits that are themselves associated with a lowered risk of dementia,” he explained.

Worth Considering

Dilip V. Jeste, MD, distinguished professor of psychiatry and neurosciences and associate dean for Healthy Aging and Senior Care at the University of California, San Diego, told Medscape Medical News that strengths of the study include its very large sample size and the different age groups followed.

“They found that people who are obese had a higher risk of developing dementia later on than people who are not obese. However, that risk varied by age group,” said Dr. Jeste, who is also past president of both the American Psychiatric Association and the American Association for Geriatric Psychiatry.

“The findings are consistent with previous reports, but there are some study limitations,” he added.

Using such a large dataset that was previously collected means having little to no control over many variables, including level of expertise in the various clinicians who made diagnoses.

In addition, the researchers did not have data on other factors that have been shown to cause dementia, including whether the patients had had head injuries or hypertension, were smokers, or carried the apolipoprotein E Ɛ4 allele.

“One study doesn’t answer all questions. Many people who are obese will not develop dementia, but obesity clearly does increase the risk of dementia. And the risk may be increased more the younger you are. That is possible,” said Dr. Jeste.

“So the study findings are useful, and they should be at least considered.”

The study authors and Dr. Jeste report no relevant financial relationships.

Postgrad Med J. Published online August 20, 2014. Abstract