Public Release: 

Smell test challenge suggests clinical benefit for some before development of Alzheimer's

Columbia University Medical Center

New York, NY (November 10, 2017) - Researchers at Columbia University Medical Center (CUMC) and the New York State Psychiatric Institute (NYSPI) may have discovered a way to use a patient's sense of smell to treat Alzheimer's disease before it ever develops. Having an impaired sense of smell is recognized as one of the early signs of cognitive decline, before the clinical onset of Alzheimer's disease. The researchers at CUMC and NYSPI have found a way to use that effect to determine if patients with mild cognitive impairment may respond to cholinesterase inhibitor drugs to treat Alzheimer's disease.

The findings were published online this week in the Journal of Alzheimer's Disease.

Cholinesterase inhibitors, such as donepezil, enhance cholinergic function by increasing the transmission of the neurotransmitter acetylcholine in the brain. Cholinergic function is impaired in individuals with Alzheimer's disease. Cholinesterase inhibitors, which block an enzyme that breaks down acetylcholine, have shown some effectiveness in improving the cognitive symptoms of Alzheimer's disease. However, they have not been proven effective as a treatment for individuals with mild cognitive impairment (MCI), a condition that markedly increases the risk of Alzheimer's disease.

"We know that cholinesterase inhibitors can make a difference for Alzheimer's patients, so we wanted to find out if we could identify patients at risk for Alzheimer's who might also benefit from this treatment," said D.P. Devanand, MBBS, MD, professor of psychiatry, scientist in the Gertrude H. Sergievsky Center at CUMC, and co-director of the Memory Disorders Clinic and the Late Life Depression Clinic at NYSPI. "Since odor identification tests have been shown to predict progression to Alzheimer's, we hypothesized that these tests would also allow us to discover which patients with MCI would be more likely to improve with donepezil treatment."

In this year-long study, 37 participants with MCI underwent odor identification testing with the University of Pennsylvania Smell Identification Test (UPSIT). The test was administered before and after using an atropine nasal spray that blocks cholinergic transmission.

The patients were then treated with donepezil for 52 weeks, and were periodically reevaluated with the UPSIT and with memory and cognitive function tests. Those who had a greater decline in UPSIT scores, indicating greater cholinergic deficits in the brain, after using the anticholinergic nasal spray test saw greater cognitive improvement with donepezil.

In addition, short-term improvement in odor identification from baseline to eight weeks tended to predict longer-term cognitive improvement with donepezil treatment over one year.

"These results, particularly if replicated in larger populations, suggest that these simple inexpensive strategies have the potential to improve the selection of patients with mild cognitive impairment who are likely to benefit from treatment with cholinesterase inhibitors like donepezil," said Dr. Devanand.

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The study is titled: "Change in Odor Identification Impairment is Associated with Improvement with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment." The other contributors are Cody Lentz (CUMC), Richard E. Chunga (NYSPI), Adam Ciarlegilio (CUMC, NYSPI), Jennifer M. Scodes (Columbia's Mailman School of Public Health), Howard Andrews (CUMC, Mailman), Peter W. Schofield (University of Newcastle, Callaghan, Australia), Yaakov Stern (CUMC), Edward D. Huey (CUMC), Karen Bell (CUMC), and Gregory H. Pelton (NYSPI, CUMC).

This study was supported in part by the Department of Defense grant W81XWH-12-1-0142 and the National Institute on Aging (R01AG041795).

Disclosures

Dr. Bell owns stock in Baxter. Dr. Devanand has received consulting fees for serving on Astellas' Scientific Advisory Board, Axovant's Educational Advisory Board, Eisai's Data Safety Monitoring Board, and Genentech's Scientific Advisory Board, and has received grants from Avanir. Dr. Stern has received consulting fees from Lilly USA, LLC, Takeda Global Research & Development Center, Inc, and Axovant Sciences, Inc. The other contributors report no financial or other conflicts of interest.

New York State Psychiatric Institute and Columbia University Department of Psychiatry (NYSPI/Columbia Psychiatry)

New York State Psychiatric Institute (founded in 1896) and the Columbia University Department of Psychiatry have been closely affiliated since 1925. Their co-location in a New York State facility on the New York-Presbyterian/Columbia University Medical Center campus provides the setting for a rich and productive collaborative relationship among scientists and physicians in a variety of disciplines. NYSPI/Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders. The Department and Institute are home to distinguished scientists noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders and childhood psychiatric disorders. Their combined expertise provides state of the art clinical care for patients, and training for the next generation of psychiatrists and psychiatric researchers.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.edu or columbiadoctors.org.

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