Noninvasive Physiomarker Identifies MCI and AD With High Accuracy
A novel physiological marker that quantifies the regulation dynamics of cerebral perfusion and oxygenation surpassed the performance of cognitive assessment tests and amyloid positron emission tomography (PET) in differentiating patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) from controls. Researchers published the finding in the journal Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring.
The marker, called the cerebrovascular dynamics index (CDI), stems from an observation researcher Vasilis Marmarelis, PhD, made 15 years ago that patients with AD showed impaired vasomotor reactivity.
“They cannot dilate the cerebral vessels to bring more blood in and provide adequate blood perfusion to the brain. This means they don’t get the oxygen, nutrients, and glucose that we need for cognition in a timely manner,” said Dr Marmarelis, of the biomedical engineering department at the University of Southern California, Los Angeles, California, in a news release.
The noninvasive CDI uses Doppler ultrasound to measure blood flow velocity in certain arteries in the brain and near-infrared spectroscopy to measure oxygenation in the front part of the cortex. The process includes predictive dynamic modeling methods that quantify how quickly and effectively the blood supply in the brain responds to subtle changes in pressure and carbon dioxide.
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The multicenter study evaluated the diagnostic performance of the CDI compared with the widely used amyloid PET standardized uptake value ratio (PET-SUVR) biomarker and 2 common cognitive screening tests: the Mini-Mental State Exam (MMSE) and the Montreal Cognitive Assessment (MoCA).
According to the study, the CDI demonstrated excellent diagnostic performance in differentiating 90 patients with MCI or AD from 77 age- and sex-matched controls. The CDI had an area under the curve of 0.96, compared with 0.78 for the PET-SUVR, 0.91 for the MMSE, and 0.92 for the MoCA.
Among the 90 patients, the CDI differentiated 56 patients with MCI from 34 patients with mild AD, with an area under the curve of 0.98. The finding suggests the marker can also be used for disease staging.
“What we have that others didn’t have before is a methodology to quantify these dynamic relations that’s extremely robust and accurate,” said Dr Marmarelis. “We can now differentiate patients with mild cognitive impairment and Alzheimer disease from cognitively normal controls far better than the PET measurement and even better than the MoCA neurocognitive test. This indicates that the particular aspect of dysregulation of cerebral perfusion regulation may be the critical aspect in the pathogenesis of this disease, probably in conjunction with other factors, including amyloid accumulation.”
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