Olfactory impairment serves as a crucial early warning marker for neurodegenerative conditions like Alzheimer’s disease and Lewy Body diseases, appearing years before other clinical symptoms manifest and predicting cognitive decline, motor function issues, and mortality among older adults.
Impairment in olfaction is a known marker of aging and neurodegenerative diseases, particularly Alzheimer’s disease and Lewy Body diseases, which encompass Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies. Both disease categories feature long prodromal periods where olfactory impairment presents years before other clinical features appear.
Data from community-based studies help test the external validity of clinic findings while remaining less vulnerable to selection biases than clinic and volunteer samples. A recent investigation leveraged information from two community-based cohorts to examine cross-sectional relationships between olfactory identification performance and multi-domain cognition, motor function, REM sleep behavior disorder-like symptoms, and APOE genotype among older adults without dementia or Parkinson’s disease.
Participant Characteristics and Initial Findings
The initial Brief Smell Identification Test data covered 787 participants, following the exclusion of five participants with dementia who had a Clinical Dementia Rating of 1 or greater, three participants with missing Clinical Dementia Rating data, and ten individuals who endorsed Parkinson’s disease diagnoses. Among the remaining participants, 670 individuals, or 85.1%, were cognitively unimpaired with a rating of zero, while 117 individuals, representing 14.9%, had a rating of 0.5 indicating mild cognitive impairment. Overall, 241 participants, or 30.6%, showed an abnormal smell test score.
Prior research demonstrates that olfactory dysfunction predicts the transition from mild cognitive impairment to dementia, future cognitive decline in unimpaired older adults, and mortality. Furthermore, impaired olfaction correlates with poor performance across various motor tasks in healthy older adults, such as slowed gait cross-sectionally and a decline in physical function over eight years.
Sleep Disorders, Biomarkers, and Genetic Risk Factors
Olfactory dysfunction also connects closely to rapid eye movement sleep behavior disorder, an early indicator of an α-synucleinopathy
. A meta-analysis identified associations supporting impaired olfaction as a durable biomarker for rapid eye movement sleep behavior disorder and prodromal Parkinson’s disease. In individuals with rapid eye movement sleep behavior disorder, hyposmia served as the strongest clinical predictor of abnormal cerebrospinal fluid aggregation of synuclein. Additionally, combining probable rapid eye movement sleep behavior disorder and olfactory deficits proved highly specific for predicting the presence of post-mortem Lewy type α-synucleinopathy
.
Evaluating specific neurodegenerative risk pathways requires probing multiple cognitive domains, such as examining memory and language for Alzheimer’s disease risk, alongside visual-spatial abilities, attention, processing speed, and executive functions for Lewy Body disease risk. Concurrently, the role of the APOE4 allele in modifying clinical and cognitive associations with olfactory deficits remains an area requiring thorough characterization.
