The high prevalence of Alzheimer’s disease in Down syndrome is associated with triplication of chromosome 21. This chromosome contains one of the genes that regulates the synthesis of amyloid beta, a short chain of amino acids that accumulates in the brain and can interfere. with brain function, resulting in cognitive impairments found in Alzheimer’s disease.
Being overweight or obese in middle age increases the risk of Alzheimer’s disease in people without Down syndrome. Fleming’s first interest was to investigate this relationship among people with Down syndrome. But the results were unexpected.
“We were interested because when we looked at weight change data and time, we saw a much stronger story of unintentional weight loss associated with early Alzheimer’s disease pathology in the brain,” says UW-Madison’s Sigan Hartley. is a professor of human development and family studies and lead author of the new study.
The study examined data from 261 people with Down syndrome aged 25 to 65 who were weighed at baseline and again approximately 18 months later. They also took a battery of cognitive tests and had brain scans to detect levels of amyloid beta and tau proteins, which are linked to Alzheimer’s disease.
Unwanted weight loss associated with amyloid development in the brain
In the study, people with Down syndrome began to lose weight unintentionally in their mid-30s, when amyloid development began. In addition, patients with Down syndrome who lose the most weight have the highest accumulation of these proteins.
“The finding that intentional weight loss coincides with the accumulation of these proteins may indicate that these processes are related or share causal pathways. This is something we will investigate next,” says Hartley.
The end result is what Hartley refers to as the weight dilemma.
“Having a higher BMI in middle age may put you at risk for Alzheimer’s disease. But Alzheimer’s disease pathology may be associated with weight loss. So both could be true,” Hartley says.
Scientific explanations for this connection between unwanted weight loss and the pathology of Alzheimer’s disease are unknown to scientists. According to one theory, amyloid accumulation causes changes in brain metabolism and hormone balance, resulting in fat and muscle loss.
Fleming’s future research will focus on how unexpected weight loss occurs, as well as disentangling the weight paradox by examining mean age BMI and the trajectory of accidental weight loss at different time points in people with Down syndrome.
“We don’t have very good clinical indications that someone might be approaching peak cognitive decline in Alzheimer’s disease,” Hartley says. “Our results are exciting because they suggest there may be some non-cognitive symptoms, including deliberate weight loss, that could help predict who will develop dementia earlier or later.”