TORONTO -- A smell test may be able to help predict cognitive decline and dementia, but it's still a long way from clinical use, researchers reported here.
In two studies presented here at the Alzheimer's Association International Conference, the University of Pennsylvania Smell Identification Test (UPSIT) predicted development of cognitive decline -- but questions about the test's specificity for distinguishing between different types of cognitive dysfunction and dementia preclude its widespread uptake, researchers said.
"Olfactory deficits have been investigated as a biomarker tool for Parkinson's, dementia with Lewy bodies, and other types of dementia, so it could be an interesting marker of an early stage of a neurodegenerative process, but I don't think it's going to be very specific to Alzheimer's disease or Parkinson's, or other neurodegenerative disorders," Eliezer Masliah, MD, head of neuroscience at the National Institute on Aging, who wasn't involved in the study, told MedPage Today.
In one study, William Kreisl, MD, of Columbia University Medical Center, and colleagues assessed 84 older adults -- some with symptoms of cognitive impairment, some without -- mean age 71 who were selected from a larger research study. They all had UPSIT testing as well as memory testing at baseline.
Patients were also assessed for amyloid burden, via either cerebrospinal fluid or amyloid PET imaging.
Over 6 months of follow-up, 67% of patients had memory decline.
In initial analyses, Kreisl and colleagues found that after correcting for age, sex, and education, amyloid positivity predicted cognitive decline, but UPSIT score did not.
However, in further analyses, they found that patients with an UPSIT score less than 35 were more likely to have memory decline than those with a score of 35 and up (OR 4.03, 95% CI 1.026 to 15.84, P=0.05).
Kreisl noted that there was "somewhat of a relationship between amyloid and UPSIT score," with those who had high scores on the sniff test having lower scores on amyloid PET -- but he warned that there "wasn't perfect agreement between amyloid status and UPSIT score."
"The two tests are not interchangeable," he said during a press briefing. "This probably has to do with beta amyloid not being the only thing driving the relationship between odor identification and memory decline. Other things, like the development of tau positive neurofibrillary tangles and breakdown and damage to areas of the brain responsible for olfactory processing may be responsible for the relationship between odor identification and memory decline."
In a second study, Seonjoo Lee, PhD, also at Columbia, and colleagues assessed 397 patients from northern Manhattan who were enrolled in the WHICAPII study, mean age 80, and followed them for 4 years.
Patients had both the sniff test and an MRI to measure entorhinal cortical thickness at baseline and again at follow up. Over that time, 50 patients developed dementia, 49 of whom developed Alzheimer's.
They found that impaired odor identification, and to a lesser degree, entorhinal cortex thickness, were predictive of the transition to dementia, and that there was a significant interaction between the two.
The UPSIT was also significant for predicting cognitive decline, but there was only a trend for entorhinal cortical thickness, Lee reported.
The findings "support the view that odor identification deficits are related to neurodegenerative changes in the entorhinal cortex during the progression of Alzheimer's," Lee said during a press briefing.
Kreisl warned that using a smell test to detect Alzheimer's disease is far from clinical use, noting that are still many steps needed in order to validate its utility. He added that there are many factors that need to be taken into account in interpreting a patient's UPSIT score, including age and gender.
Also, there are not yet well defined cutoffs for predicting cognitive decline or dementia, he said.
"These vary somewhat from study to study, because of the size of the samples, the qualities of the people in each study, how each study is administered, and how we're defining cognitive decline and dementia," he said.
Even once larger studies are done and cutoffs more established, and if the tests makes it way into clinical use, "it's still going to need to be used with caution, as an additional tool in a clinician's toolbox," Kreisl said. "It should not be used in and of itself to diagnose dementia or dementia risk. It would need to be used in the context of the patient, patient history, other ancillary test, clinical exam findings, and so on."
The studies were supported by grants from the National Institute on Aging.
The authors disclosed no financial relationships with industry.
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