Sniffing Out Alzheimer Disease

    Our nose helps us identify odors, from a cup of coffee to the smoke of a cigarette. As we age, an impaired sense of smell is normal, but completely losing our sense of smell could be a sign of brain damage.

    What if it were possible to predict cognitive decline and detect the early stages of Alzheimer’s disease (AD) based on the results of an odor identification test? A group of New York neuroscientists believes this is possible on the basis of their recent discoveries. Researchers from Columbia University Medical Center (CUMC), New York State Psychiatric Institute, and NewYork–Presbyterian presented data at the Alzheimer’s Association’s International Conference in Toronto from two studies that suggest the University of Pennsylvania Smell Identification Test (UPSIT) may offer a practical, low-cost alternative to other current diagnostic tools for predicting AD. Medicilon's Pharmacodynamics Department can deliver multiple nervous system models based on anti-depressants, anti-Alzheimer's drugs, sedative-hypnotic and anti-anxiety drugs, analgesics, anti-convulsants, anti-Parkinson's drugs, and anti-schizophrenia drugs.

    In one study—”Predictive Utility of Entorhinal Cortex Thinning and Odor Identification Test for Transition to Dementia and Cognitive Decline in an Urban Community Population”—the researchers administered the UPSIT to 397 older adults (average age of 80 years) without dementia in a multiethnic population. Each of the participants also had an magnetic resonance imaging (MRI) scan to measure the thickness of the entorhinal cortex—the first area of the brain known to be affected by Alzheimer’s disease.

    After a 4-year follow-up, 50 of the study participants (12.6%) had developed dementia, and nearly 20% had signs of cognitive decline. Interestingly, the researchers found that low UPSIT scores—which indicate decreased ability to identify odors correctly—but not entorhinal cortical thickness, were significantly associated with dementia and Alzheimer’s disease.

    Moreover, the investigators found that low UPSIT scores, but not entorhinal cortical thickness, were predictive of cognitive decline, yet entorhinal cortical thickness was significantly associated with the UPSIT score in those who transitioned to dementia.

    “Our research showed that odor identification impairment, and to a lesser degree, entorhinal cortical thickness, were predictors of the transition to dementia,” explained presenting author Seonjoo Lee, Ph.D., assistant professor of clinical biostatistics at CUMC. “These findings support odor identification as an early predictor, and suggest that impairment in odor identification may precede thinning in the entorhinal cortex in the early clinical stage of Alzheimer’s disease.”

    In the second study—”Both Odor Identification and Amyloid Status Predict Memory Decline in Older Adults”—researchers evaluated the usefulness of the UPSIT and tests that measure the amount of amyloid protein in the brain for predicting memory decline. The team administered the UPSIT and performed either beta-amyloid positron emission tomography (PET) scanning or analysis of cerebrospinal fluid in 84 older adults (median age of 71 years). Of these participants, 58 (69%) had mild cognitive impairment.

    At follow-up, at least 6 months later, 67% of the participants had signs of memory decline. Testing positive for amyloid with either method, but not the UPSIT score, predicted cognitive decline. However, participants with a score of less than 35 were more than three times as likely to have memory decline as those with higher UPSIT scores.

    “Our research suggests that both UPSIT score and amyloid status predict memory decline,” noted study author William Kreisl, M.D., assistant professor of neurology in the Taub Institute at CUMC and a neurologist at NewYork–Presbyterian/Columbia. “Younger age, higher education, and shorter follow-up may explain why UPSIT did not predict decline as strongly in this study as in previous studies. Although more research is needed, odor identification testing, which is much less expensive and easier to administer than PET imaging or lumbar puncture, may prove to be a useful tool in helping physicians counsel patients who are concerned about their risk of memory loss.”

    Currently, clinical diagnostic methods for detecting AD are only able to do so for later stages of AD, when significant brain damage has already occurred. Brain imaging with PET may show the buildup of amyloid plaques in the brain years before symptoms appear; however, this method is expensive. Tests such as beta-amyloid detection in cerebrospinal fluid and brain PET imaging of abnormal tau protein are rapidly advancing through research. Adding a rapid, low-cost diagnostic is of extreme value to physicians and patients, as steps to slow the progression of the disease could potentially begin at a much early age.

    “Our study adds to the growing body of evidence demonstrating the potential value of odor identification testing in the detection of early-stage Alzheimer’s disease,” remarked senior author on both studies D.P. Devanand, M.D., professor of psychiatry at CUMC.

    “Using other biomarkers of Alzheimer’s disease to detect the disease at an earlier stage—which have the potential to be lower-cost and noninvasive—could lead to dramatic improvements in early detection and management of the disease,” commented Heather Snyder, Ph.D., director of medical and scientific operations at the Alzheimer’s Association.