An analysis of international data on more than a million people who were followed over time confirms two links between BMI and dementia — one ties midlife obesity to higher risk, and the other ties being underweight near disease onset to higher risk.

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New research clarifies how both obesity and lower-than-average BMI are linked to dementia.

A report on the longitudinal study, which was conducted by researchers across Europe and led by University College London (UCL) in the United Kingdom, is published in the journal Alzheimer’s & Dementia.

The findings may explain the mixed evidence on the relationship between higher body mass index (BMI) and dementia risk; there is some that points to higher BMI being tied to raised risk, and there is some that suggests the opposite.

The reason for the confusion is because there are two things going on, says lead study author Mika Kivimäki, who is a professor in UCL’s Institute of Epidemiology & Health.

“One is an adverse effect of excess body fat on dementia risk,” he notes. “The other is weight loss due to preclinical dementia.”

This might explain why those who develop dementia tend to have above-average BMI two decades before disease symptoms appear, but nearer the time of onset, their BMI is lower than healthy counterparts who do not develop it.

Worldwide, there are around 47 million people living with dementia, an irreversible, deteriorating brain disease that progressively diminishes ability to remember, think, and live independently.

The risk of developing dementia rises with age, and because of the rising number of elderly people in the world, global numbers of the disease are soaring.

As there is currently no cure for dementia, or even treatments that slow it down, the already huge impact that the disease has on individuals, their families, communities, health systems, and costs will become overwhelming.

Estimates suggest that by 2030, there will be 75 million people living with dementia worldwide, rising to 132 million by 2050.

Alzheimer’s disease — a condition that gradually destroys cells and tissue in the brain — is the main cause of dementia, accounting for around 65 percent of cases.

While estimates vary, it is thought that there are around 5 million people living with Alzheimer’s disease in the United States, where dementia is a leading cause of death among older people.

For their new study, Prof. Kivimäki and colleagues pooled and analyzed data from 39 longitudinal population studies.

Altogether, the data covered a total of 1,349,857 individuals from France, Finland, Sweden, the U.K., and the U.S. All were free of dementia when they enrolled and underwent measurement of weight and height to assess their BMI.

By searching hospital and prescription records and death registries, the studies had established that 6,894 of the participants developed dementia over 38 years of follow-up.

When they analyzed the data, the team found that having higher BMI 20 years before onset of dementia was linked to higher risk of the disease.

In addition, they found that the risk of dementia rose by between 16 and 33 percent for each five-unit rise in BMI.

Five units of BMI are roughly the difference between normal and overweight and the difference between overweight and obese on the BMI scale. For a person of height 5 feet 7 inches (170 centimeters), this is equal to 14.5 kilograms (32 pounds).

By contrast, the researchers found that the average BMI of those who developed dementia was lower in the preclinical stage just before disease onset compared with healthy counterparts who did not develop it.

They conclude that when taken together, their findings suggest that the link between BMI and dementia is due to two separate processes: in one, higher BMI serves to raise disease risk long before symptoms develop, and in the other — which they describe as “reverse causation” — the preclinical stage of the disease results in lower BMI.

“By dissecting these processes in stratified analyses,” they note, “our study provides a plausible explanation for the inconsistencies in some of the prior studies on BMI and dementia.”

The team suggests that further studies are needed in order to determine what mechanisms might drive weight loss in the preclinical stage.

Maybe damage to thinking and memory causes people to take less care of themselves, or perhaps there is loss of appetite due to reduced ability to smell and changes in feelings of fulness or disturbed metabolism.

They also explain that the studies should explore whether the link with BMI is the same for all types of dementia, such as Alzheimer’s disease, frontotemporal dementia, Lewy body dementia, and vascular dementia.

The new study confirms both the adverse effect of obesity as well as weight loss caused by metabolic changes during the pre-dementia stage.”

Prof. Mika Kivimäki