Megan Brooks

July 27, 2016

TORONTO ― The University of Pennsylvania Smell Identification Test (UPSIT) has potential as an inexpensive, noninvasive test to help diagnose Alzheimer's disease, a new study shows.

In a study of older adults, both a low score on the UPSIT and positive amyloid beta (Aβ) status predicted memory decline.

"Reduced ability to identify odors has been seen in patients who are later diagnosed with Alzheimer's disease at autopsy. And decreased odor identification is also seen in those with mild memory symptoms and those who develop Alzheimer's disease dementia," said William Kreisl, MD, from the Taub Institute and Columbia University Medical Center in New York City.

He presented the study at a press briefing here at the Alzheimer's Association International Conference (AAIC) 2016.

Low-Cost Alternative to PET?

The investigators compared the predictive utility of odor identification impairment using the UPSIT with that of amyloid status, as determined by 11C-Pittsburgh Compound B (PIB) positron- emission tomography (PET) scanning or cerebrospinal fluid (CSF) analysis, in predicting memory decline.

Participants included 84 elderly adults from the Questionable Dementia II study who had either mild cognitive impairment (MCI) or normal memory at baseline. They had undergone either brain amyloid PET scanning or lumbar puncture at baseline and at a minimum of 6 months' follow-up.

Amyloid positivity was defined as either CSF Aβ42 < 192 pg/mL or global PIB uptake > 1.5. Memory decline was defined as 1 standard deviation (SD) decrease over 4 years or 0.5 SD over 2 years on composite z-score from Logical Memory 1, Visual Reproduction, and Free and Cued Selective Reminding tests.

During follow-up, 67% of participants showed memory decline. After correcting for age, sex, and education, both amyloid positivity and a low UPSIT score (<35 of 40) significantly predicted memory decline, the researchers found.

Participants with a low UPSIT score were more than three times more likely to experience memory decline than those with a UPSIT score >35 (odds ratio, 3.95; P = .0192).

There also was "somewhat of a relationship between odor identification and beta-amyloid status in that those with a high UPSIT score tended to have lower amounts of amyloid on the PET scan," Dr Kreisl said. "However, there was not perfect agreement between amyloid status and UPSIT score, so the two tests are not interchangeable," he noted.

He also noted that the UPSIT did not predict decline as strongly in this study as has been seen in other studies. He suggested that this may due to the relatively younger age and higher educational status of the participants in the current study. The sample size was also relatively small, owing to the high cost of PET imaging.

"Despite these limitations, we conclude that UPSIT may be useful in evaluating patients who are concerned about their memory as a low-cost, noninvasive alternative to PET scan or spinal tap in assisting physicians in determining a patient's risk of one day developing Alzheimer's disease," Dr Kreisl said.

Potential Biomarker

Briefing moderator Suzanne Craft, PhD, Wake Forest School of Medicine, Winston-Salem, North Carolina, said this study shows that "properties of smell can predict cognitive decline, and the ability to identify odors may be a very early sign or harbinger of future cognitive decline as well as the presence of Alzheimer's pathology in terms of beta-amyloid, and further, that smell identification may be a correlate of beta-amyloid and has the potential to serve as a surrogate for the more expensive and invasive techniques, like amyloid imaging."

Dr Craft, who is a member of the Alzheimer's Association Medical and Scientific Advisory Council, said there is an "urgent need for biomarkers for Alzheimer's disease that are simple and easily attainable, something similar to blood pressure."

Problems with odor identification is one "very interesting" possibility, she said. "The sense of smell is supported by neurogenesis and is very strongly associated with memory, and it is thought by some that that connection might make it a very useful surrogate for what might be going on in the brain," Dr Craft added.

The study was funded by the National Institute on Aging. The authors have disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2016. Abstract O3-12-01. Presented July 26, 2016.

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