COPENHAGEN – A test that measures how well patients recognize scents was highly correlated with progression from mild cognitive impairment to Alzheimer’s disease as well as neurodegeneration and beta-amyloid deposition in the brain in two separate studies.
Although the test is not ready for use in the clinic, it has the potential to be part of a panel of screening tests to predict the development of Alzheimer’s disease, researchers said at a press briefing during the Alzheimer’s Association International Conference 2014.
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For patients with Alzheimer's, the test is a measure of memory, revealing an inability to recall once-familiar scent associations.
Timely detection of asymptomatic patients is currently lacking, said Dr. David S. Knopman, who moderated the session.
"Our principal clinical tools, including PET and MRI imaging, are excellent, but they are of little value for detecting patients in the preclinical stage of the disease," said Dr. Knopman, professor of neurology at the Mayo Clinic, Rochester, Minn. "These tests, on the other hand, are much simpler, less expensive and invasive, and would be feasible to use in the field, as opposed to only in a large research center."
The studies used the 40-item University of Pennsylvania Smell Identification Test (UPSIT), a scratch-and-sniff test that measures anosmia of mild, moderate, or severe levels, and costs about $25. For patients with Alzheimer’s disease, the test is a measure of memory, revealing an inability to recall once-familiar scent associations.
In one study, Matthew Growdon, a fourth-year medical student at Harvard University, Boston, and his colleagues found a significant relationship between olfactory impairment and pathologic markers of Alzheimer’s disease. The study involved 212 participants of the ongoing Harvard Aging Brain Study, which seeks to identify structural brain changes associated with memory impairment in aging. Participants were cognitively and physically healthy at baseline.
The investigators administered the UPSIT to all subjects, who also underwent a full evaluation to detect signs and symptoms of Alzheimer’s disease. The evaluation included cognitive testing, structural brain scanning, and amyloid imaging, as well as genetic testing and obtaining blood and spinal fluid biomarkers.
A linear regression model evaluated associations between the UPSIT and amyloid burden, hippocampal size, and thinning of the entorhinal cortex. A separate model looked at associations between UPSIT scores and memory test results.
A total of 100 participants were high performers, scoring in the upper 75th percentile of both the UPSIT and the memory tests. The remaining 112 were considered low performers. Of these, 59 scored in the lower 25th percentile of the UPSIT, but in the upper 25th percentile of memory. Nineteen scored in the upper 75th percentile of the UPSIT but the lower 25th percentile of memory, and 34 in the lower 25th percentile of both the UPSIT and memory.
The investigators found a linear correlation between poor UPSIT performance and both lower hippocampal volume on MRI and higher amyloid burden based on Pittsburgh compound B PET imaging. There was a marginal association between poorer UPSIT scores and entorhinal cortex thinning, Mr. Growdon noted.
The associations may indicate that Alzheimer’s pathology affects neurons in the olfactory bulb as well as other brain regions, said Mr. Growdon. "We seem to be looking at neuronal death in all these regions. And what’s really interesting is that this could be the basis of a very simple, low-cost screening tool for a clinically normal, asymptomatic older population. I envision it as something that could flag those at risk of developing symptoms or as a gateway to more expensive or invasive testing.
"It’s not ready for prime-time, though. This is a snapshot of a single moment in time. We would need longitudinal studies before it could be incorporated into care – maybe as part of a panel of screening tests," he said.
Dr. Davangere Devanand presented a second, unrelated study in which he and his colleagues measured the association between olfactory identification impairment and progression from mild cognitive impairment to Alzheimer’s dementia.
The investigation followed 757 participants of the Northern Manhattan Study, a multiethnic community sample in New York that has been used in large part to examine stroke risk factors. The participants initially took the UPSIT during 2004-2006, followed by additional testing during 2006-2008 and 2008-2010.
A total of 109 transitioned from normal cognition to mild cognitive impairment, and then 101 progressed to Alzheimer’s disease.
A low score on the UPSIT test significantly predicted the development of Alzheimer’s with a specificity of 65%. For each one-point decline in UPSIT score, the risk of developing Alzheimer’s increased by 5%.