Weight gain promotes brain ageing

Excess body weight, especially in the form of overweight or obesity, is linked to accelerated brain ageing and increased cerebral atrophy, most notably among men.

This is the finding of the largest international study to date on the relationship between body weight and brain health. Published in the journal eBioMedicine, the study involved more than 46,000 participants across 15 research projects.

The researchers employed advanced brain imaging techniques and machine learning algorithms to examine individuals who were overweight or obese but had not been diagnosed with cognitive impairment. The aim was to determine whether excess weight might silently contribute to brain ageing or to a loss of brain volume similar to that observed in Alzheimer’s disease.

“From the in-depth analysis of this large dataset of brain MRI scans, it was found a connection between obesity and brain ageing: a phenomenon more pronounced in men than in women, and with effects that decrease with age,” explains Filippos Anagnostakis, first author of the study, research affiliate at the University of Pennsylvania and Columbia University, and a recent graduate in Medicine from the University of Bologna.

Anagnostakis carried out this research during his studies at the University of Bologna, in collaboration with scholars from several US universities, including Harvard University and the University of California – San Francisco.

“The results we obtained - the researcher adds - offer a valuable opportunity for reflection: they encourage us to rethink the impact of obesity not only in aesthetic terms, but also in relation to brain health”.

Obesity is considered by many to be a global epidemic of our century, with estimates indicating that by 2050 more than half of the world's adult population will be overweight or obese. This condition is associated with metabolic, cardiovascular and renal disorders which, together with population ageing, threaten the health of an increasing number of people.

Moreover, we now know that weight gain in adult life is associated with a higher risk of developing dementia. A high body mass index is thought to compromise brain integrity, leading to atrophy of grey and white matter and impairing the stability of neural circuits. However, we do not yet know the mechanisms behind these phenomena.

To investigate the possible connection between overweight, obesity and brain health, the researchers therefore analysed the MRI scans of over 46,000 people.

“The data show that excessive body weight is associated with accelerated brain aging and greater celebral atrophy, compared with people of normal weight: brain changes resembling those observed in the early stages of Alzheimer’s disease,” says Anagnostakis. “This is particularly true for men: those who were overweight had a brain that appeared about eight months ‘older’, while in men with obesity brain ageing was approximately two years greater than that of peers of normal weight”.

The findings were different for women. The findings were different for women. Surprisingly, the study found that women of normal weight displayed more signs of brain ageing and Alzheimer’s-like atrophy than overweight women and even than men of normal weight.

We know that sex differences influence the risk of developing dementia in distinct ways, but the pathways driving these disparities remain to be clarified”, comments Anagnostakis.

Age also proved to be a central factor. The impact of body weight on brain ageing was stronger in younger individuals, while it tended to weaken with advancing age.

Many aspects related to these connections remain to be understood. Some clues emerged from the proteomic analyses conducted by the team, that is, the large-scale study of proteins. Several blood proteins were identified that are associated both with body weight and brain ageing.

“Brain MRI analyses and proteomic analyses suggest the existence of common biological mechanisms linking weight gain and brain ageing”, confirms Anagnostakis. “However, many unknowns remain to be addressed in order to uncover these connections and to understand the specific mechanisms behind sex-related differences”.

The study was published in eBioMedicine  under the title "Radiomic and proteomic signatures of body mass index on brain ageing and Alzheimer's-like patterns of brain atrophy".