The new findings — which are published in the journal Alzheimer's & Dementia — are thought to be the first to suggest that higher levels of branched-chain amino acids in a person's blood could be a marker for a lower risk of developing dementia.
Branched-chain amino acids are essential nutrients that the body needs and gets from protein-rich foods such as legumes and meat.
In their report, co-senior study author Sudha Seshadri — a professor of neurology at the University of Texas, San Antonio — and colleagues explain that scientists are starting to realize that dementia is not a straightforward disease.
In fact, they say that there is an increasing need to address its prevention and treatment with a "multipronged approach."
Traditionally, researchers have mainly looked for answers in the brain — where, for instance, some hallmarks of Alzheimer's disease, one of the main types of dementia, are found in the form of faulty tau and amyloid proteins.
Now, however, more of the searching has widened to include other parts of the body, such as the bloodstream, which has an intimate relationship with the brain.
"It is now recognized," Prof. Seshadri notes, "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."
Alzheimer's disease and dementia
Dementia is a brain-wasting disease that gradually robs us of our ability to remember, think, reason, communicate, and take care of ourselves. Alzheimer's is the most common form.
There are around 47 million people in the world living with dementia, 65 percent of whom have Alzheimer's disease.
In the United States, there are more than 5 million people living with Alzheimer's disease, and this number is expected to reach 16 million by 2050.
The cost of Alzheimer's disease and other forms of dementia in the U.S. is also expected to rise, from $259 billion per year in 2017 to $1.1 trillion in 2050.
Blood sample results and rates of dementia
For their study, the researchers used information and samples from eight studies that had followed large groups of people of European ancestry in five countries over a long period. They also had records of the incidence of Alzheimer's disease or other forms of dementia in those groups.
In this way, they were able to obtain data and stored baseline blood samples for a total of 22,623 participants, who were free of dementia at baseline and also had no history of stroke or "other neurological disease affecting cognitive function."
Altogether, the dataset covered 246,698 person-years, during which "995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively," note the authors.
Using nuclear magnetic resonance and mass spectrometry metabolomics, they identified and quantified "blood metabolites, lipid, and lipoprotein lipids" in the baseline blood samples.
They then ran statistical tests to look for any associations between the baseline quantities of the various molecules and the cases of dementia and Alzheimer's disease that arose among the participants during the follow-up.
Various molecules linked to risk
The results showed that some of the baseline blood molecules were associated with a lower risk of dementia, while others were associated with a higher risk.
There was a similar finding for association with risk of Alzheimer's disease: some of the molecules were linked to lower risk, and others to higher risk.
The details of these associations were as follows:
- Lower dementia risk was linked to: the branched-chain amino acids isoleucine, leucine, and valine; creatinine; and two very low-density lipoprotein (VLDL) subclasses.
- Lower Alzheimer's risk was similarly linked to branched-chain amino acids.
- Increased risk of dementia was linked to one high-density lipoprotein (HDL) and one VLDL subclass.
- Higher risk of Alzheimer's disease was also linked to an HDL subclass.
The authors note that, to their knowledge, theirs is the first study to have reported a link between higher levels of branched-chain amino acids and clinical dementia.
They suggest that their results may do more than show that changes in the blood can be measured years before dementia is diagnosed. They hope that they will also widen the search for much-needed new drugs for Alzheimer's disease and other forms of dementia.
"It is exciting to find new biomarkers that can help us identify persons who are at the highest risk of dementia."
Prof. Sudha Seshadri