Obesity gene linked to dementia: Swedish study

The new research has found a genetic link between obesity and Alzheimer’s disease, according to Caroline Graff, lead researcher of the study published in the February issue of the Journal of Alzheimer’s Disease.

The FTO genotype has shown a small but robust effect on body mass index (BMI) and increase the risk for diabetes, according to the study.

Both high BMI and diabetes are vascular risk factors that can play a role in the development of Alzheimer’s disease and dementia, the researchers said.

“In a way, the finding that surprises us most is that when we correct for BMI, we still see the effect. We thought the effect would work through a higher BMI,” Graff told The Local on Monday.

“One explanation may be that those we examined were already way into the disease. That could explain why their BMI was already lower, but we don’t know whether this effect is independent of BMI or not,” she added.

She explained that while the subjects with the genotype were not necessarily obese during the study, it is “very likely” that they were previously overweight.

The study’s aim was to explore the impact of FTO on the risk of developing Alzheimer’s and dementia.

Nine years of follow-up data was gathered from the Kungsholmen project, a population-based study of 1,003 individuals over the age of 75 who did not have or had not yet been diagnosed with dementia at the start.

Half of the participants had the genotype.

Other factors taken into account included Apolipoprotein E (APOE), physical inactivity, BMI, diabetes and cardiovascular disease.

Compared to carriers of the FTO TT-genotype, AA-carriers had a higher risk for both Alzheimer’s and dementia after adjustment for age, gender, education and APOE genotype.

This effect remained after additional adjustment for physical inactivity, BMI, diabetes and cardiovascular disease. An interaction between FTO and APOE was found, with increased risk for dementia for those carrying both FTO-AA and APOE e4.

The effect of the AA-genotype on dementia and Alzheimer’s risk seems to act mostly through the interaction with APOE e4, according to Graff.

“We do not know if the genotype is doing something to the brain or if it has a handle on other biological mechanisms,” she said.

The findings suggest that the FTO AA-genotype increases the risk for dementia and in particular Alzheimer’s, independently of physical inactivity, BMI, diabetes and cardiovascular disease measured at baseline.

The results are in line with the recently reported association between FTO and reduced brain volume in cognitively healthy subjects.

Graff is currently conducting the same study on a younger group of subjects aged 60 and older, also in Kungsholmen, through the Swedish National Study on Ageing and Care (Snac).

“We will see if this risk can be seen earlier and collect more information on BMI and cardiovascular disease. We want to collect more data on BMI earlier in life in our subjects,” she explained.

In addition, through the study, Graff and her colleagues learned that BMI is associated with smaller brain volumes in different parts of the brain, so they will conduct MRI scans on a subgroup of people, see if the FTO risk genotype has a developmental effect on smaller brain volumes.

Previously, lower BMI was associated with a higher risk of developing dementia, but at the time, the BMI was measured just a few years before the onset of the disease, when individuals were already eating and exercising less.

“Now we can see 20 years between dementia onset. One should be aware of effect of BMI on health, not only on cardiovascular diseases, but dementia. If you have a high BMI, you can do something about it,” said Graff.