Related Experiment Video
Updated: Aug 25, 2025
Olfactory Assays for Mouse Models of Neurodegenerative Disease
Published on: August 25, 2014
Olfactory Dysfunction and Incidence of Motoric Cognitive Risk Syndrome: A Prospective Clinical-Pathologic Study
Nigel L Kravatz1, Emmeline Ayers2, David A Bennett1
1From the Department of Neurology (N.L.K., E.A., J.V.), Albert Einstein College of Medicine, Bronx, NY; Rush Alzheimer's Disease Center (D.A.B.), Rush University Medical Center, Chicago, IL; and Department of Medicine (J.V.), Albert Einstein College of Medicine, Bronx, NY.
Background And Objectives:
To examine associations between olfactory dysfunction, Alzheimer disease (AD) pathology, and motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait that is associated with risk for AD and other dementias.
Methods:
We conducted a retrospective analysis of a prospective cohort study to examine whether baseline olfactory function was associated with the risk of incident MCR in 1,119 adults aged 60 years and older (75.1% female). The association between performance on the Brief Smell Identification Test (BSIT) and incident MCR risk was computed using Cox models and reported as the hazard ratio (HR) with 95% CIs adjusted for demographic, comorbidity, and cognitive factors. Furthermore, we assessed the relationship between postmortem AD pathology and non-AD pathology and olfactory function at the time of MCR diagnosis using linear regression models adjusted for sex, education, age at death, and time from diagnosis to death.
Results:
There were 544 (48.6%) incident cases of MCR over a median follow-up of 3.94 years. Lower BSIT scores (poor olfaction) at baseline were associated with an increased risk of incident MCR (HR for a 1-point increase in BSIT score 0.92; 95% CI 0.88-0.96) in fully adjusted models. Those with hyposmia (scores of ≤8 on the BSIT) at baseline (26.6%) were at an increased risk of MCR (HR 1.44; 95% CI 1.19-1.74) compared with those with normal olfactory function. Higher levels of the composite measure of global AD pathology and presence of Lewy body pathology were associated with lower BSIT scores at the time of incident MCR diagnosis (n = 118). τ tangle density, a specific component of AD pathology, was inversely associated with olfactory function, and the correlation remained after controlling for mild cognitive impairment syndrome and the presence of Lewy body pathology.
Discussion:
The results provide evidence that olfactory dysfunction precedes MCR incidence and is related to Alzheimer pathology, providing a clinical approach to risk stratify and subtype MCR.
Insights
Olfactory dysfunction, or impaired sense of smell, is linked to a higher risk of developing motoric cognitive risk syndrome (MCR). This smell impairment is also associated with Alzheimer disease pathology, suggesting potential for early risk stratification.
Area of Science:
- Neuroscience
- Gerontology
- Pathology
Background:
- Motoric cognitive risk syndrome (MCR) is a predementia syndrome characterized by cognitive complaints and slow gait.
- MCR is associated with an increased risk for Alzheimer disease (AD) and other dementias.
- Olfactory dysfunction is a potential early marker for neurodegenerative diseases.
Purpose of the Study:
- To investigate the association between olfactory dysfunction and the risk of incident MCR.
- To explore the relationship between olfactory function and Alzheimer disease pathology in individuals with MCR.
Main Methods:
- Retrospective analysis of a prospective cohort study involving 1,119 adults aged 60+.
- Baseline olfactory function assessed using the Brief Smell Identification Test (BSIT).
- Cox models used to compute MCR risk; linear regression models assessed pathology-olfaction relationship postmortem.
Main Results:
- Lower BSIT scores (poorer olfaction) were associated with increased MCR risk (HR 0.92 per point increase).
- Hyposmia (BSIT score ≤8) at baseline increased MCR risk (HR 1.44).
- Higher global AD pathology and Lewy body pathology correlated with lower BSIT scores at MCR diagnosis; tau tangle density inversely associated with olfaction.
Conclusions:
- Olfactory dysfunction precedes MCR incidence, indicating its potential as an early clinical marker.
- The findings link olfactory dysfunction to Alzheimer pathology, supporting its role in MCR.
- Olfactory assessment may aid in risk stratification and subtyping of MCR.
Related Concept Videos
01:03Olfactory Receptors: Location and Structure
01:25Olfaction
The olfactory receptors are embedded in the cilia of the...
01:20Physiology of Smell and Olfactory Pathway
The olfactory...
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:24Prosopagnosia