Lower weight in late life may increase risk of Alzheimer's Disease

August 2, 2016, Massachusetts General Hospital

Researchers at Brigham and Women's Hospital (BWH) and Massachusetts General Hospital (MGH) have found an association between lower weight and more extensive deposits of the Alzheimer's-associated protein beta-amyloid in the brains of cognitively normal older individuals. The association—reported in the Journal of Alzheimer's Disease—was seen in particular among individuals carrying the APOE4 gene variant, which is known to increase the risk of Alzheimer's.

"Elevated cortical amyloid is believed to be the first stage of the preclinical form of Alzheimer's disease, so our findings suggest that individuals who are underweight late in life may be at greater risk for this disease," says Gad Marshall, MD, of the MGH and BWH Departments of Neurology, senior author of the report. "Finding this association with a strong marker of Alzheimer's disease risk reinforces the idea that being underweight as you get older may not be a good thing when it comes to your brain health."

While the concept of a preclinical version of Alzheimer's disease is theoretical and not yet being used to guide clinical diagnosis or treatment, the current hypothesis involves three stages. Individuals at stage 1 are cognitively normal but have elevated amyloid deposits; stage 2 adds evidence of neurodegeneration, such as elevated tau deposits or characteristic loss of certain brain tissues, with no cognitive symptoms; and stage 3 adds cognitive changes that, while still in a normal range, indicate a decline for that individual. The current study is part of the MGH-based Harvard Aging Brain Study (HABS), designed to identify markers that predict who is likely to develop Alzheimer's disease and how soon symptoms are likely to develop.

This investigation explored the relationship between body mass index (BMI) and beta amyloid levels in the brains of the first 280 participants to enroll in HABS, who were ages 62 to 90, cognitively normal and in good general health. Participants' initial enrollment data included medical histories; physical exams; testing for the presence of APOE4, the major genetic risk factor for late-onset Alzheimer's; and PET imaging with Pittsburgh compound B (PiB), which can visualize amyloid plaques in the brain.

After adjusting for factors including age, sex, education and APOE4 status, researchers found that having a lower BMI was associated with greater retention of PiB, indicating more extensive in the brain. The association was most pronounced in normal-weight participants, who were the group with the lowest BMI in the study. Analysis focused on APOE status revealed that the association between lower BMI and greater PiB retention was particularly significant for individuals with the APOE4 gene variant, which is associated with increased Alzheimer's disease risk.

Researchers hope that future studies will explain the mechanism behind the association between lower BMI and increased amyloid levels. "A likely explanation for the association is that low BMI is an indicator for frailty - a syndrome involving reduced weight, slower movement and loss of strength that is known to be associated with Alzheimer's risk," says Marshall, who is an assistant professor of Neurology at Harvard Medical School. "One way to get closer to determining any cause and effect relationship will be following these individuals over time to see whether their baseline BMI does predict the development of symptoms, which we are doing in HABS, and eventually investigating whether maintaining or even increasing BMI in late life has an effect on outcomes. Right now, we're also studying whether BMI is associated with any other clinical and imaging markers of Alzheimer's disease."

Explore further: Using tau imaging as diagnostic marker for Alzheimer disease

More information: Journal of Alzheimer's Disease, DOI: 10.3233/JAD-150987

Related Stories

Using tau imaging as diagnostic marker for Alzheimer disease

July 25, 2016
The accumulation of β-Amyloid (Αβ) and tau proteins in the brain is hallmark pathology for Alzheimer disease. Recently developed positron emission tomography (PET) tracers, including [18F]-AV-1451, bind to tau in neurofibrillary ...

New approaches to understanding Alzheimer's and Parkinson's disease

July 26, 2016
In a study presented today at the Alzheimer's Association International Conference 2016, researchers at the Douglas Mental Health University Institute have explored how some people may develop the hallmarks of Alzheimer's ...

Estrogen patch in newly postmenopausal women may reduce Alzheimer's risk

July 12, 2016
Can estrogen preserve brain function and decrease the risk of Alzheimer's disease when given early in menopause? Newly postmenopausal women who received estrogen via a skin patch had reduced beta-amyloid deposits, the sticky ...

'Pac-Man' gene implicated in Alzheimer's disease

July 26, 2016
A gene that protects the brain from the harmful build-up of amyloid-beta, one of the causative proteins implicated in Alzheimer's disease, has been identified as a new target for therapy by NeuRA researchers.

PET imaging with special tracer can detect and diagnose early Alzheimer's disease

May 24, 2016
The effort to find ways to detect and diagnose preclinical Alzheimer's disease (AD) has taken a big step forward with the use of positron emission tomography (PET), a "nuclear medicine" for imaging processes in the body, ...

Recommended for you

Meditation and music may alter blood markers of cellular aging and Alzheimer's disease

November 13, 2018
A research team led by Dr. Kim Innes, a professor in the West Virginia University School of Public Health, has found that a simple meditation or music listening program may alter certain biomarkers of cellular aging and Alzheimer's ...

Alzheimer's and cardiovascular disease share common genetics in some patients

November 9, 2018
Genetics may predispose some people to both Alzheimer's disease and high levels of blood lipids such as cholesterol, a common feature of cardiovascular disease, according to a new study by an international team of researchers ...

Artificial intelligence predicts Alzheimer's years before diagnosis

November 6, 2018
Artificial intelligence (AI) technology improves the ability of brain imaging to predict Alzheimer's disease, according to a study published in the journal Radiology.

Diabetes medications may reduce Alzheimer's disease severity

November 1, 2018
People with Alzheimer's disease who were treated with diabetes drugs showed considerably fewer markers of the disease—including abnormal microvasculature and disregulated gene expressions—in their brains compared to Alzheimer's ...

Massive study confirms that loneliness increases risk of dementia

October 29, 2018
A new Florida State University College of Medicine study involving data from 12,000 participants collected over 10 years confirms the heavy toll that loneliness can take on your health: It increases your risk of dementia ...

Bioactive compound from the Rhodiola plant improves memory

October 25, 2018
In an ageing society, more people are suffering from memory disorders. The progressive loss of memory severely impairs the quality of life of those affected. So far, no drugs are known to prevent age-related cognitive decline.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.