Being skinny in mid-life can up your Alzheimer's risk

Turns out, being skinny may not be all it's cracked up to be as a recent study has found a link between a lower weight and early Alzheimer's disease.

Researchers at Brigham and Women's Hospital (BWH) and Massachusetts General Hospital (MGH) 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 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," said senior author Gad Marshall.

He added, "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.

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.

Researchers hope that future studies will explain the mechanism behind the association between lower BMI and increased amyloid levels.

Marshall concluded, "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."

The study is reported in the Journal of Alzheimer's Disease.