Summary: Columbia researchers have identified a way in which to determin if a patient with MCI may respond to cholinesterase inhibitors.
Source: Columbia University Medical Center.
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.
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).
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.
Funding: This study was supported in part by the Department of Defense grant W81XWH-12-1-0142 and the National Institute on Aging (R01AG041795).
Source: Gregory Flynn – Columbia University Medical Center
Publisher: Organized by NeuroscienceNews.com.
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Original Research: The study will appear in Journal of Alzheimer’s Disease.