Smell test reflects brain pathologies, risk of Alzheimer’s

A scratch – and sniff test that asks subjects to identify 40 odors and ranks olfaction is almost as powerful as a predictor of Alzheimer’s disease is a positive test of amyloid.

Low scores on the University of Pennsylvania Smell Identification Test (UPSIT) are linked to a thinning of the entorhinal cortex – the brain region where amyloid plaques are thought to first appear as Alzheimer’s disease takes hold, reported at the Alzheimer’s Association International Conference.

The findings indirectly suggest that impairment in odor identification may precede thinning in the entorhinal cortex in the early clinical stage of AD.

According to him, poor UPSIT sores are also related to brain levels of amyloid beta and are almost as predictive of cognitive decline.

These sensory changes appear to be one of the earliest manifestations of Alzheimer’s disease, the researcher said at the Alzheimer’s Association International Conference. Their studies also suggest that the test has a place in the clinic as an easy and inexpensive screening tool for patients with memory complaints said at the Alzheimer’s Association International Conference.

The amyloid biomarker tests currently available are not suitable for wide dissemination. Amyloid brain scans are currently investigative; and not covered by Medicare or any private insurance. Lumbar punctures are also invasive and expensive and almost universally disliked by patients. In addition, there is little consensus on how to interpret CSF amyloid levels.

“We need easy, noninvasive biomarkers that can be deployed in the clinic for patients who are concerned about their risk of memory decline,” said Columbia University Medical Center, New York.

His study concluded that the UPSIT predicted Alzheimer’s disease almost as well as invasive amyloid biomarkers. The scratch - and - sniff test asks subjects to identify 40 odors and ranks olfaction as a normal or mildly, moderately, or severely impaired.

He examined the relationship between UPSIT and brain amyloid beta in 84 subjects, 58 of whom had mild cognitive impairment (MCI) at baseline. All of these subjects had either an amyloid brain scan or lumbar puncture to measure amyloid in cerebrospinal fluid. They were followed for at least six months.

At follow-up, 67 percent of the group of participants showed cognitive decline. After correction for age, gender, and education, patients who were amyloid- positive on imaging or in CSF were more than seven times as likely to have experienced cognitive decline. However, when it was imputed as a continuous variable, patients with a score of less than 35 on the 40-item test were four times more likely to show cognitive decline than those with a score of 35 or higher.

In fact, these low UPSIT scores were much more common among amyloid-positive patients. Of the 38 patients who were positive for amyloid beta on either diagnostic test, 32 had an UPSIT score less than 35, while six had a score of 35 or greater. Among the 46 amyloid-negative patients, 28 had low UPSIT scores, and 18 had normal UPSIT scores.

A separate study examined the relationship of UPSIT performance to entorhinal cortical thickness in 397 cognitively healthy subjects who were involved in the Washington Heights-Inwood Columbia Aging Project. These subjects took the UPSIT and had magnetic resonance brain imaging both at baseline and at four years’ follow-up. Over that time, 50 transitioned to dementia, and 49 of them were diagnosed with Alzheimer’s disease. Another 79 subjects experienced cognitive decline.

In comparing the groups with and without dementia, he found significant differences in the follow-up UPSIT score (23 vs. 27) and entorhinal cortical thickness (2.9 vs. 3.1 mm).

One standard deviation in performance on the UPSIT score was associated with a significant 47 percent increase in the risk of dementia, while one standard deviation in entorhinal cortical thickness was associated with a 22 percent increase in the risk. However, he said, the interaction of entorhinal thickness and UPSIT score was significant only in the group of subjects who transitioned to dementia.