Emerging research suggests newly identified blood markers can predict the risk for future dementia. Investigators believe the biomarkers will help to detect individuals who are at the highest risk of dementia, moving beyond current methods that rely on discovery of beta-amyloid plaques in the brain.
In the study, investigators at University of Texas Health San Antonio analyzed small molecules (called metabolites) in blood samples drawn from 22,623 individuals, including 995 who went on to develop dementia.
The participants were enrolled in eight research cohorts in five countries.
Researchers found that higher blood concentrations of molecules called branched-chain amino acids were associated with lower risk of future dementia. Another molecule, creatinine, and two very low-density lipoprotein (VLDL)-specific lipoprotein lipid subclasses also were associated with lower risk of dementia.
One high-density lipoprotein (HDL) and one VLDL lipoprotein subclass were associated with increased dementia risk.
Sudha Seshadri, M.D., is the co-leader and senior author on the research which appears in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The findings are important as dementia is a rising tidal wave of devastation for families and society with age being the biggest risk factor.
Alzheimer’s disease, which is the leading cause of dementia, is the sixth-leading cause of death in the United States, and more than five million Americans are currently living with Alzheimer’s — a figure expected to triple by 2050.
The research findings will broaden the search for drug targets in dementia caused by Alzheimer’s disease, vascular disease, and other subtypes, said Dr. Seshadri.
“It is now recognized that we need to look beyond the traditionally studied amyloid and tau pathways and understand the entire spectrum of pathology involved in persons who present with symptoms of Alzheimer’s disease and other dementias,” explains Seshadri.
“It is exciting to find new biomarkers that can help us identify persons who are at the highest risk of dementia.”
In the future, researchers may investigate the feasibility of developing a diagnostic exam, such as a blood test, to assess each patient’s molecular signature of dementia risk. The signature could include blood concentration of branched-chain amino acids.
Branched-chain amino acids are nutrients that the body obtains from proteins in foods such as meat and legumes. These amino acids include leucine, isoleucine and valine.
The altered metabolite signatures were observed years before the diagnosis of dementia when those study participants were healthy, Dr. Seshadri said. Therefore, if a test were to become available, therapy could be initiated earlier.
The study evaluated persons of European ancestry and was carried out in collaboration with researchers in Finland, the Netherlands, the United Kingdom, and Estonia. Seshadri is eager to replicate it in South Texas so as to evaluate diverse racial and ethnic groups.
Investigators see a potential linkage as valine is a amino acid which has previously been shown to be involved in determining the risk of diabetes. Diabetes is a large concern among the Hispanic population living in South Texas, says Seshadri.
“Now it is shown to be associated with the risk of Alzheimer’s dementia. We want to investigate for any connections.”
Metabolites are influenced by genetic and environmental factors, and their levels can be modified through dietary and pharmacological interventions. “I hope that people reading about this study will understand that they can take ownership of their health,” Dr. Seshadri said.
“The lifestyle decisions they make, such as adopting a Mediterranean or other healthful diet, can affect these metabolites in ways we do not fully understand.”
Moreover, further studies can clarify whether the branched-chain amino acids and other molecules play a causal role in the dementia disease process or are merely early markers of the disease, explains Seshadri.