Blood test may predict dementia risk in people with REM sleep disorder
Levels of 2 proteins tied to Dementia with Lewy Bodies diagnosis in a few years
Among people with rapid eye movement (REM) sleep behavior disorder, blood biomarkers associated with dementia may help identify those at risk of developing Dementia with Lewy Bodies (DLB), a condition that shares symptoms with Parkinson’s disease.
Particularly, blood levels of two proteins — amyloid-beta 42/40 ratio and p-tau 181 — significantly linked, respectively, with a 10 and 15 times higher risk of DLB. These biomarkers have been used to detect Alzheimer’s disease, the most common form of dementia.
“Detecting dementia risk early could have significant implications for how doctors guide patients, helping them plan for the future and potentially allowing for more personalized, effective treatments,” Ronald Postuma, MD, PhD, professor in the division of neurology at McGill University in Canada, said in a university news story.
Researchers now plan to confirm the test’s accuracy in predicting dementia risk in Parkinson’s patients and other groups at risk for DLB.
REM sleep behavior disorder is known to associate with Parkinson’s
The study, “Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder,” was published in the journal Brain.
Parkinson’s is caused by the progressive dysfunction and death of nerve cells that produce dopamine, a brain signaling molecule. A key driver of neuronal loss is the formation of Lewy bodies, which are toxic protein clumps mainly composed of alpha-synuclein.
Lewy bodies also are found in people with DLB, a condition characterized by cognitive issues. Besides the deposition of alpha-synuclein, those with DLB may present biomarkers associated with Alzheimer’s disease, including blood amyloid-beta and tau proteins.
Researchers at the Montreal university, along with scientists at Roche, aimed to understand whether blood biomarkers of Alzheimer’s could help to predict DLB risk in people with REM sleep disorder, a condition marked by physically acting out dreams. REM sleep disorder is known to closely associate with Parkinson’s, often appearing years before that disease’s motor symptoms are evident.
They conducted a study at Hôpital du Sacré-Coeur de Montréal that enrolled 144 adults with idiopathic, or unknown cause, REM sleep behavior disorder (iRBD). After an average of almost three years after blood tests were taken, 32 patients developed a neurodegenerative disease, mostly DLB (18 people) and Parkinson’s (13 people). The remaining adult was diagnosed with multiple system atrophy, which also shares symptoms with Parkinson’s disease.
People with these neurodegenerative conditions were older than those who went without them (mean age of 66.7 vs. 70.6 when blood sample taken). Those who developed DLB were older, on average, than those who went on to develop Parkinson’s (73.3 vs. 68.2).
Of the two measured blood biomarkers, the amyloid-beta 42/40 ratio reflects the presence of toxic amyloid-beta protein clumps, and p-tau 181 is linked to tau aggregation.
DLB diagnosed in people with significantly higher or lower protein levels
People who developed DLB had significantly lower levels of the amyloid-beta 42/40 ratio in their blood at its sampling, and significantly higher levels of p-tau 181 than the 110 patients who did not develop a neurodegenerative disease. However, when comparing people who later developed Parkinson’s to those who did not, these “differences were less clear,” the researchers noted. Specifically, the amyloid-beta 42/40 ratio was lower in those who with Parkinson’s, but no significant difference was seen in p-tau181 levels.
“The primary finding of this study is that blood [amyloid-beta] 42/40 and pTau181 can predict development of DLB in iRBD. This is true for both biomarkers, but pTau181 seems particularly useful,” the researchers wrote.
When grouped by mild cognitive impairment (MCI) status, people who went on to a Parkinson’s diagnosis with evident MCI had lower amyloid-beta 42/40 levels, similar to those who later developed DLB. But their p-tau 181 levels did not significantly differ. In contrast, those who developed Parkinson’s but not MCI had amyloid-beta 42/40 and p-tau 181 levels similar to those without any neurological diagnosis over the study’s years.
When grouping people based on normal and abnormal Montreal Cognitive Assessment scores, which measure cognitive function, those in either group who later developed DLB had lower amyloid-beta 42/40 levels and higher p-tau 181 levels compared with people who did convert to a neurological disease.
People with an amyloid-beta 42/40 ratio below 0.112 picograms/milliliter (pg/mL) in the blood were found to have a 10 times higher risk of DLB, while p-tau 181 levels above 0.802 pg/mL raised this risk by 15.5 times, analyses showed.
Proteins as blood markers of eventual ‘primary dementia or parkinsonism’
“Our findings suggest that plasma [amyloid-beta]42/40 ratio and pTau181 can predict [DLB] outcome in iRBD. In certain iRBD patients, plasma markers of amyloid-[beta] and/or tau can predict whether patients will ultimately develop primary dementia or parkinsonism,” the researchers wrote.
Patients’ cognitive performance, including memory, attention, and executive function, was closely linked to p-tau 181 blood levels. Generally, higher p-tau 181 levels were associated with a poorer performance in cognitive tests, such as verbal fluency, memory recall, and attention tasks.
Data for the ApoE genotype was available for 106 people, 21 of whom carried the ApoE4 variant, the highest genetic risk factor for dementia. These adults had significantly lower amyloid-beta 42/40 levels than those without this variant, while no differences were found for p-tau 181 levels.
“Our findings suggest that Alzheimer’s treatments could also be tested in patients with this sleep disorder,” said Aline Delva, MD, PhD, and the study’s lead author and a research follow at the Montreal Neurological Institute-Hospital during the study. “Perhaps, if treatments start early enough, dementia with Lewy bodies can be prevented.”
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