Saliva-Based Test Proposed to Diagnose Alzheimer’s, Mild Cognitive Impairment

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by Jonathan Grinstein |

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A new test using patients’ saliva may be helpful in distinguishing between Alzheimer’s, mild cognitive impairment, and normal brain function, new research reports.

The study, “Alzheimer’s Biomarkers From Multiple Modalities Selectively Discriminate Clinical Status: Relative Importance of Salivary Metabolomics Panels, Genetic, Lifestyle, Cognitive, Functional Health and Demographic Risk Markers,” was published in Frontiers in Aging Neuroscience.

Recent projections show that the worldwide incidence of dementia-related neurodegenerative diseases, especially Alzheimer’s disease, is increasing dramatically. Also, clinical trials have yet to produce successful therapeutics to reverse or prevent the course of neurodegeneration-related dementia in aging after diagnosis. Consequently, research and clinical attention has shifted to identifying possible risk factors prior to the development of symptoms to promote early management of Alzheimer’s.

“So far, no disease-altering interventions for Alzheimer’s disease have been successful,” Roger Dixon, PhD, University of Alberta, said in a press release. “For this reason, researchers are aiming to discover the earliest signals of the disease so that prevention protocols can be implemented.”

To this end, researchers have been trying to identify biomarkers — measurable indicators of disease — in addition to the established hallmarks of Alzheimer’s disease (i.e., amyloid plaque and neurofibrillary tangle accumulation) to diagnose Alzheimer’s at the earliest possible stage. Also, due to limitations in examining the brain in living patients, there is a need for Alzheimer’s and other neurodegenerative disease diagnostics that are non-invasive (not requiring the introduction of instruments into the body).

For these reasons, researchers at the University of Alberta sought to identify non-invasive biomarkers that could distinguish between Alzheimer’s disease, mild cognitive impairment, or normal cognition.

A total of 82 individuals participated in the research. Cognitive normal (35 people, age 64–75, 62.9% female) and mild cognitive impairment (25 people, age 64–75, 60% female) individuals were drawn from a subset of participants from the Victoria Longitudinal Study (VLS) who participated in the VLS biofluid and genetics initiative (2009–2012). The VLS is a long-term, large-scale investigation of human aging. Alzheimer’s patients (22 people, age 52–91, 72.7% female) were recruited from the Geriatric and Cognitive Clinic at the Glenrose Rehabilitation Hospital (Edmonton).

The researchers compared a comprehensive list of biomarkers from six risk factor groups: metabolomic (relating to the small molecule intermediates and products of metabolism), genetic (e.g., Apolipoprotein E (APOE) mutations), lifestyle (e.g., lack of exercise), cognitive (e.g., learning and memory dysfunction), functional health (e.g., cardiovascular issues), and bio-demographic (e.g., male or female).

Saliva is of interest in biomarker research for brain-related diseases because it can be acquired easily. The other four biomarker groups are similarly non-invasive because they are acquired through observation.

Three important discriminative predictors were identified that could clinically distinguish between Alzheimer’s and normal cognition individuals, namely two cognitive measures — poorer memory performance and slower speed performance — and higher levels (greater risk) of the Alzheimer’s metabolite panel.

The same two cognitive predictors and the metabolite panel were identified as important predictors to distinguish between Alzheimer’s and mild cognitive impairment.

The most important predictors for discriminating mild cognitive impairment from cognition normal were: higher pulse pressure, higher levels of the mild cognitive impairment metabolite panel, poorer memory performance, lower frequency of novel cognitive activity, elevated APOE risk, decreased social activity, and lower Mini-Mental State Exam (MMSE) score (a 30-point questionnaire widely used to measure cognitive function).

“In this analysis, we found three metabolites that can be used to differentiate between these three groups,” said Liang Li, PhD, professor in the Department of Chemistry University of Alberta.

“This is preliminary work, because we’ve used a very small sample size. But the results are very promising. If we can use a larger set of samples, we can validate our findings and develop a saliva test of Alzheimer’s disease.”

This research shows that combinations of different biomarker groups both modifiable (lifestyle) and non-modifiable (genetic), are informative and can be useful in the diagnosis of neurodegenerative disease.

Researchers believe these results lay the groundwork for the use of non-invasive tests consisting of combinations of metabolomic and other biomarker risk factors for the early diagnosis of Alzheimer’s disease and other neurodegenerative diseases.