Obesity May Increase Cognitive Decline via Inflammation

Liam Davenport

October 24, 2016

Being overweight or obese leads to clinically meaningful increases in the rate of cognitive decline in association with changes in inflammatory markers in the blood, a new analysis of longitudinal data suggests.

The results, which indicate that an increased body mass index (BMI) may accelerate cognitive decline by several months via increases in serum C-reactive protein (CRP) levels, may help explain those of previous studies that link obesity with poorer brain health.

"The findings provide a clear and integrative account of how BMI is associated with cognitive decline through systemic inflammation, but we need to remember that these are only correlational findings," lead author Kyle Bourassa, a PhD candidate in the Department of Psychology, University of Arizona, in Tuscon, said in a release.

"Of course, correlation does not equal causation. The findings suggest a mechanistic pathway, but we cannot confirm causality until we reduce body mass experimentally, then examine the downstream effects on inflammation and cognition," he added.

The study was published online September 19 in Brain, Behavior, and Immunity.

Inflammation the Culprit?

As previously reported by Medscape Medical News, an Australian analysis of adults in their 60s indicated that being overweight or obese was associated with smaller hippocampal volume at baseline and greater hippocampal atrophy over 8 years.

Another recent study suggested that in obese individuals, white matter volume was significantly smaller than in persons who were lean, although this was not tied to a decrease in cognitive function.

In the current study, investigators tested the hypothesis that systemic inflammation may mediate the association between body mass and cognitive function. The researchers examine data from the English Longitudinal Study of Ageing, in which data were collected in seven waves every 2 years from 1998 to 2013.

Cognitive measures, which included three tasks that tested memory and executive functioning, were assessed every 2 years from wave 1 to wave 5. In addition, BMI was determined, and blood samples were collected every 4 years from wave 0 to wave 6. From these, CRP levels were calculated.

Data were available across at least one of the waves for 29,808 unique participants. From these, the team selected two samples of 9066 people and 12,652 individuals, respectively, who had completed five waves of the study.

This yielded three time points for analysis in each subsample: T1, at which BMI, CRP levels, and cognitive performance were measured; T2, when CRP levels were again measured; and T3, when the cognitive tasks were readministered.

Focusing initially on memory performance, the team found that that BMI at T2 significantly predicted the change in CRP levels in each subsample (P < .001 for both subsamples). Furthermore, CRP levels at T2 significantly predicted T3 memory performance when baseline cognition was taken into account (P < .001 for both subsamples).

This led to a significant indirect effect of T1 BMI on T3 memory performance via T2 CRP levels (P = .001 for subsample 1 and P = .007 for subsample 2).

A similar pattern was seen with respect to executive function. T1 BMI significantly predicted CRP change (P < .001 for both subsamples), and T3 CRP levels significantly predicted T3 executive function (P = .003 for subsample 1 and P < .001 for subsample 2).

Again, this was underlined by a significant indirect effect of T1 BMI on T3 executive function via T2 CRP levels (P = .006 in subsample 1 and P = .003 in subsample 2).

The results held when the researchers took into account known predictors of cognitive decline, including depressive symptoms, self-rated health, the presence of heart pain, reported myocardial infarction, and the use of medication for high blood pressure during the past 2 years.

The team calculated that a change of 1 standard deviation (SD) in age, or 10.39 years, predicted a 0.28 SD average change in cognition. In comparison, a 1 SD change in body mass, which equates to 4.34 BMI points, or approximately 26 lb for someone of the average height, predicted a 0.12 SD change in CRP (0.25 mg/L). This, in turn, predicted a 0.05 SD change in cognition.

This means that, with respect to chronologic age, a change in initial body mass of 1 SD would be associated with approximately 2.22 months of cognitive decline, whereas a 1 SD change in CRP would be associated with 1.85 years of cognitive decline.

"Although these effects are small, they do appear to be comparable with the above lengths of chronological aging, suggesting they are clinically meaningful," the investigators write.

Bourassa told Medscape Medical News that "just looking at the health literature tells us that...being overweight is bad for you" and that the current findings are "adding to the idea that not only are we going to see effects on people's physical health but also in terms of their cognition.

"I think this is really just adding one more piece of the puzzle in terms of why being overweight puts you at risk for a whole variety of negative things," he added.

He said that "one of the more important points" to come out of this study is that the findings also point to ways in which cognition decline could be tackled.

"It's essential when we look at links like this that the next step would be thinking about what kind of intervention studies could we do to either change people's BMI or change their inflammation, and see if we see changes in their cognition down the line.

"The gold standard study would be taking aging adults and giving them a weight intervention and seeing, if they reduce their weight, does this lead to decreases in their inflammation and then down the line increases in their cognition? That would obviously be pretty exciting, because it would tell us that we can target BMI as a way to impact not only people's health but also their cognition."

Funding for the study was provided by the National Institute of Aging in the United States and a consortium of UK government departments coordinated by the Office for National Statistics. The authors have disclosed no relevant financial relationship.

Brain Behav Immun. Published online September 16, 2016. Abstract

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