Weight loss may be an indicator of increased risk of developing Alzheimer's disease

A team from the Pasqual Maragall Foundation's research centre, the Barcelonaβeta Brain Research Center (BBRC), with the support of the "la Caixa" Foundation, has detected that people at increased risk of developing Alzheimer's disease show a weight loss that could predict the cognitive deterioration of the disease.

"We have detected that weight loss can predict the presence of altered biomarkers of Alzheimer's disease, such as the accumulation of Tau and Beta-amyloid proteins in the brain, in people without cognitive alterations," explains Dr. Oriol Grau, first author of the research and researcher at the BBRC. The accumulation of these proteins indicates an increased risk of developing Alzheimer's disease, and begins to be detected up to 20 years before the manifestation of the first cognitive symptoms. Despite this, having them does not necessarily mean that dementia will develop.

The study has been published in the journal Alzheimer's Research & Therapy and has also involved researchers from the Hospital Clínic de Barcelona, Roche Diagnostics International, the University Hospital of Sweden, the Center for Biomedical Research Network on Fragility and Healthy Aging (CIBERFES) and the Center for Biomedical Research Network on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN).

To carry out the research, the researchers analysed the association between changes in body weight and biomarkers of Alzheimer's disease in 408 participants without cognitive alterations in the Alfa + Study, promoted by the "la Caixa" Foundation. The participants underwent different visits separated by an interval of four years on average, and underwent a series of cognitive, clinical and neuroimaging tests.

The results of the study reveal that participants at higher risk of Alzheimer's had lost an average of 1% of their body weight per year, while participants at lower risk, on average, had experienced no weight loss during the follow-up period. These differences were observed when taking into account other potential causes of changes in body weight, such as cardiovascular risk factors or levels of anxiety and depression.

Until now, epidemiological studies have shown that weight loss can occur a decade before the onset of dementia, but its role as a predictor of the presence of biomarkers in the preclinical phase of the disease has been little studied.

"One of the hypotheses that has been developed is that Alzheimer's disease would directly affect a brain structure called the hypothalamus; this region, apart from other functions, also regulates the body's metabolism and energy expenditure. Consequently, its alterations could lead to changes in body weight," explains Dr Oriol Grau.

On its own, weight loss alone is not a useful benchmark for determining Alzheimer's risk, as it can derive from many reasons. However, Dr Grau points out that "incorporating an indicator of changes in body weight into risk indices that encompass different measures can help predict which people are most at risk of developing cognitive impairment associated with Alzheimer's disease".

The study opens the door to including this measure, along with other established risk factors, to provide more tools for determining Alzheimer's risk.

"Keeping this indicator in mind would allow closer monitoring of patients with cognitive complaints who also have weight loss, as well as facilitating the identification of people who could benefit from more specific tests or possible prevention strategies," concludes Dr Grau.

Grau-Rivera O, Navalpotro-Gomez I, Sánchez-Benavides G, Suárez-Calvet M, Milà- Alomà M, Arenaza-Urquijo EM, Salvadó G, Sala-Vila A, Shekari M, González-de- Echávarri JM, Minguillón C, Niñerola-Baizán A, Perissinotti A, Simon M, Kollmorgen G, Zetterberg H, Blennow K, Gispert JD, Molinuevo JL; ALFA Study. Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease. Alzheimers Res Ther. 2021 Feb 17;13(1):46. doi: 10.1186/s13195-021-00781-z. PMID: 33597012; PMCID: PMC7890889.

Every three seconds a new case of dementia is diagnosed worldwide, and it is estimated that there are currently 50 million people affected, in most cases due to Alzheimer's disease. In Spain, this figure translates into more than 900,000 people. With life expectancy on the rise, if no treatment is found to prevent or slow the course of the disease, the number of cases could triple by 2050, and reach epidemic proportions, as the latest World Alzheimer Report 2018 published by Alzheimer's Disease International points out.

The Barcelonaβeta Brain Research Center (BBRC) is the research centre of the Pasqual Maragall Foundation, promoted by the "la Caixa" Foundation since its creation, dedicated to the prevention of Alzheimer's disease and the study of cognitive functions affected in healthy and pathological ageing.

The Pasqual Maragall Foundation is a non-profit organisation that was set up in April 2008 in response to the commitment made by Pasqual Maragall, former Mayor of Barcelona and former President of the Generalitat de Catalunya, when he publicly announced that he had been diagnosed with Alzheimer's disease. The Foundation's mission is to promote research to prevent Alzheimer's disease and to offer solutions that improve the quality of life of those affected and their carers.