Biomarkers of amyloid and tau pathology are hallmarks of Alzheimer’s disease. However, identifying them necessitates expensive neuroimaging or an invasive lumbar puncture, which are financially and physically onerous. Seeking to identify a simpler, cost-effective alternative, Davangere P. Devanand, MD, director of geriatric psychiatry and co-founder of the Memory Disorders Center at NewYork-Presbyterian and Columbia, and his colleagues conducted a study looking at the role of olfactory deficits as a potential non-invasive biomarker to predict cognitive decline and dementia. Below, Dr. Devanand discusses the findings from their recent study and its implications for diagnosing cognitive decline and potential for Alzheimer’s disease onset in the future.
While a person’s sensitivity to smell is present in the early stages of Alzheimer’s, as the disease progresses patients lose their ability to distinguish and identify smells.
— Dr. Davangere Devanand
The Connection Between Memory and Smell
Identifying who will develop cognitive decline indicative of Alzheimer’s disease before symptoms develop is an ongoing challenge for neurological and geriatric memory disorder specialists. While a person’s sensitivity to smell is present in the early stages of Alzheimer’s, patients lose their ability to distinguish and identify smells. The brain regions in the olfactory pathways that code for memories of smells and naming them are damaged early on in Alzheimer’s. The olfactory pathway in the brain is very near the entorhinal cortex and hippocampus, which are responsible to a large extent for memory. So it’s not surprising that if these regions are damaged, the olfaction code and the way the brain interprets it is also damaged.
Research Goals
While there has been a lot of research focused on the detection of biomarkers of amyloid and tau pathology, most studies have not looked at the predictive value of combining brain imaging biomarkers and olfaction deficits.
Our study sought to determine whether odor identification testing paired with a cognitive screening test is comparable to amyloid PET imaging as a useful clinical tool to predict risk of developing Alzheimer’s. We wanted to see if performing the non-invasive olfaction and cognitive tests together would be as effective brain imaging with PET. This screening approach would be of great value, particularly in locations where amyloid imaging is not readily available.
Research Methods
For our study, we drew on data from the ongoing 20-year Mayo Clinic Study of Aging in which participants underwent PET and MRI to detect biomarkers of amyloid and tau pathology, as well as had an olfaction test.
We ended up evaluating data on 647 participants who had several clinical markers and biomarkers that predict cognitive decline or dementia during an average eight-year follow-up. Each subject underwent baseline screening with the modified Blessed Information Memory Concentration Test (BIMCT); a Brief Smell Identification Test (BSIT); and structural brain MRI and PET imaging.
Global cognition was ascertained using a modified version of the BIMCT, which included 16 items of orientation, judgment, abstract reasoning, serial subtractions, and short-term recall of a sentence. Scores ranged from 0 to 20, with higher scores indicating greater cognitive performance.
The BSIT consisted of six food-related and six non-food-related smells – cherry, clove, strawberry, menthol, pineapple, lemon, leather, lilac, smoke, soap, natural gas, and rose. Participants selected one of four possible choices for each item. Based on published data, a BSIT score ≤ 8 out of 12 was considered an olfactory deficit and a score ≥ 9 was considered normal.
We found that combining the olfaction test with a brief cognitive test was as accurate as PET brain imaging in predicting who would decline cognitively or develop Alzheimer’s disease.
— Dr. Davangere Devanand
Key Findings
We found that combining the olfaction test with a brief cognitive test was as accurate as PET brain imaging in predicting who would decline cognitively or develop Alzheimer’s disease. While most of the participants were relatively normal in terms of their cognitive test performance, we did find that these measures predicted who would progress to cognitive decline. Notably, we are talking about mild deficits in both olfaction and cognition that many people would not even notice. The study allowed us to compare participant test scores to their amyloid imaging results to draw conclusions as to their significance.
We found that cognitive decline developed in 102 study participants and dementia in 34 participants. Identification of olfaction deficits and impairment in global cognition was comparable to PET for predicting cognitive decline and dementia. While these findings were not unexpected, their importance is of great value as amyloid imaging is usually only accessible at an academic medical center or in a metropolitan area and is very expensive. Individuals who have cognitive concerns want to know if they represent normal aging or are indicative of potential dementia onset. These simple tests conducted in the clinic have the potential to assist the clinician in determining whether an individual is at high risk for declining cognitively or developing Alzheimer’s. However, these tests alone are not diagnostic as cognitive and olfactory deficits can occur in other conditions, and taking the whole clinical picture into account is very important before making a differential diagnosis.
Future Implications
We are now beginning to build on this research looking at identifying other biomarkers. Plasma levels of amyloid beta protein are being developed as blood biomarkers for Alzheimer’s. These are now shown to be closely related to both amyloid and tau imaging abnormalities. Establishing these blood biomarkers is likely as initial studies are very promising. The focus would then shift to clinical applications. For example, would we draw blood to test for tau and amyloid in the clinic? Do we perform the olfaction and cognitive tests? Or do we do all of these? That work is just getting underway.
