Summary: McGill university researchers have devised a new odor identification test that could help doctors predict those at risk of Alzheimer’s and track the progression of the disease.
Source: McGill University.
Promising finding suggests odour identification tests may help scientists track the evolution of the disease in persons at risk.
By the time you start losing your memory, it’s almost too late. That’s because the damage to your brain associated with Alzheimer’s disease (AD) may already have been going on for as long as twenty years. Which is why there is so much scientific interest in finding ways to detect the presence of the disease early on. Scientists now believe that simple odour identification tests may help track the progression of the disease before symptoms actually appear, particularly among those at risk.
“Despite all the research in the area, no effective treatment has yet been found for AD,” says Dr. John Breitner, the director of the Centre for Studies on Prevention of Alzheimer’s Disease at the Douglas Mental Health Research Centre of McGill University. He is one of the authors of the study on the subject that was recently published in the journal Neurology. “But, if we can delay the onset of symptoms by just five years, we should be able to reduce the prevalence and severity of these symptoms by more than 50%.”
Bubble gum or gasoline?
Close to 300 people with an average age of 63 who are at risk of developing AD because they had a parent who had suffered from the disease, were asked to take multiple choice scratch-and-sniff tests to identify scents as varied as bubble gum, gasoline or the smell of a lemon. One hundred of them also volunteered to have regular lumbar punctures to measure the quantities of various AD-related proteins whose presence in the cerebrospinal fluid (CSF).
The researchers found that those with the most difficulty in identifying odours were those in whom other, purely biological indicators of AD, were most evident.
“This is the first time that anyone has been able to show clearly that the loss of the ability to identify smells is correlated with biological markers indicating the advance of the disease,” says Marie-Elyse Lafaille-Magnan, a doctoral student at McGill and the first author on the study. “For more than 30 years, scientists have been exploring the connection between memory loss and the difficulty that patients may have in identifying different odours. This makes sense because it’s known that the olfactory bulb (involved with the sense of smell) and the entorhinal cortex (involved with memory and naming of odours) are among the first brain structures first to be affected by the disease.”
“This means that a simple smell test may potentially be able to give us information about the progression of the disease that is similar to the much more invasive and expensive tests of the cerebrospinal fluid that are currently being used,” the director of research program on Aging, Cognition and Alzheimer’s disease of the Douglas Institute and one of the authors on the study. “However, problems identifying smells may be indicative of other medical conditions apart from AD and so should not be substituted for the current tests.”
The researchers caution more that far more work needs to be done to see how changes in a person’s ability to identify smells over time relates to the progression of the disease itself. For the time being, smell tests are simply one more avenue to explore as researchers look for ways to identify the disease before the symptoms actually begin to appear.
Funding: The research was funded by Pfizer Canada, the Canada Fund for Innovation, Fonds de recherche du Québec-Santé, the Levesque Foundation, the Douglas Mental Health University Institute Foundation.
Source: McGill University
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Original Research: Abstract for “Odor identification as a biomarker of preclinical AD in older adults at risk” by Marie-Elyse Lafaille-Magnan, BSc, MSc, Judes Poirier, PhD, CQ, Pierre Etienne, MD, Jennifer Tremblay-Mercier, MSc, Joanne Frenette, BSN, MN, Pedro Rosa-Neto, MD, PhD, John C.S. Breitner, MD, MPH; For the PREVENT-AD Research Group in Neurology. Published online July 25 2017 doi:10.1212/WNL.0000000000004159
Odor identification as a biomarker of preclinical AD in older adults at risk
Objective: To assess odor identification (OI) as an indicator of presymptomatic Alzheimer disease (AD) pathogenesis in cognitively normal aging individuals at increased risk of AD dementia.
Methods: In 274 members of the PREVENT-AD cohort of healthy aging persons with a parental or multiple-sibling history of AD dementia, we assessed the cross-sectional association of OI with potential indicators of presymptomatic AD. Some 101 participants donated CSF, thus enabling assessment of AD pathology with the biomarkers total tau (t-tau), phospho-tau (P181-tau), and their ratios with β-amyloid (Aβ1-42). Adjusted analyses considered age, cognition, APOE ε4 status, education, and sex as covariates. We measured OI using the University of Pennsylvania Smell Identification Test and cognitive performance using the Repeatable Battery for Assessment of Neuropsychological Status. Standard kits provided assays of the AD biomarkers. Analyses used robust-fit linear regression models.
Results: Reduced OI was associated with lower cognitive score and older age, as well as increased ratios of CSF t-tau and P181-tau to Aβ1-42 (all p < 0.02). However, the observed associations of OI with age and cognition were unapparent in adjusted models that restricted observations to CSF donors and included AD biomarkers. OI showed little association with CSF Aβ1-42 alone except in APOE ε4 carriers having lowest-quartile Aβ1-42 levels.
Conclusions: These findings from healthy high-risk older individuals suggest that OI reflects degree of preclinical AD pathology, while its relationships with age and cognition result from the association of these latter variables with such pathology. Diminished OI may be a practical and affordable biomarker of AD pathology.
“Odor identification as a biomarker of preclinical AD in older adults at risk” by Marie-Elyse Lafaille-Magnan, BSc, MSc, Judes Poirier, PhD, CQ, Pierre Etienne, MD, Jennifer Tremblay-Mercier, MSc, Joanne Frenette, BSN, MN, Pedro Rosa-Neto, MD, PhD, John C.S. Breitner, MD, MPH; For the PREVENT-AD Research Group in Neurology. Published online July 25 2017 doi:10.1212/WNL.0000000000004159