Severe olfactory impairment may be an early marker of Alzheimer’s disease
Anosmia is associated with abnormalities in neuroimaging measures of amyloid and neurodegeneration that are present in the preclinical stage of Alzheimer’s disease (AD), according to a study. This suggests the potential utility of olfactory assessment for identifying early AD in cognitively normal older adults.
“Although olfactory assessment cannot currently be used as a standalone diagnostic test, a combination of olfactory assessment with other AD biomarkers (eg, imaging biomarkers) could strengthen the AD diagnostic sensitivity and specificity,” said study co-author Dr Rosebud O. Roberts from the Mayo Clinic in Rochester, Minnesota, US.
Roberts and colleagues examined the cross-sectional associations between neuroimaging measures of amyloid accumulation and neurodegeneration and a simple measure of odour identification (Brief Smell Identification Test) among 829 older adults (mean age 79.2 years; 51.5 percent male) who were cognitively normal. Analysis were performed using multinomial logistic regression and simple linear regression models.
Of the participants, 9.4 percent had anosmia and 60.7 percent had hyposmia. Magnetic resonance imaging findings showed that significantly more participants with anosmia had abnormal AD signature cortical thickness and hippocampal volume (p<0.001 for both). [Ann Neurol 2017;81:871–882]
Moreover, among those with available positron emission tomography scans, the proportion of those with abnormalities in amyloid accumulation and brain metabolism were similarly greater, although nonsignificantly, among participants with anosmia.
Abnormal AD signature cortical thickness and reduced hippocampal volume were particularly associated with worse olfactory function (p=0.01 and p<0.01, respectively). The odds of having anosmia were more than twofold higher for individuals with abnormalities in amyloid accumulation (adjusted odds ratio [aOR], 2.74; 95 percent CI, 1.12 to 6.66), cortical thickness (aOR, 2.20; 1.25 to 3.86) and hippocampal volume (aOR, 2.45; 1.21, 4.94).
“The association of imaging biomarker abnormalities with [olfactory impairment] suggests that odour identification may be a noninvasive, inexpensive marker for … identifying participants at the preclinical stage of AD who may be at risk for cognitive impairment,” Roberts said.
She noted a need for inexpensive noninvasive tests to identify older healthy persons potentially at risk of AD for enrolment in prevention trials.
Despite the presence of limitations, the authors pointed out that olfactory assessment has potential clinical significance if validated prospectively.
The olfactory system has been shown to be one of the earliest brain regions affected by AD, suggesting that olfactory impairment could be an early sign of AD brain pathology. [J Alzheimers Dis 2010;22:1081-1087; BMC Neurol 2014;14:168]
In cognitively normal elderly individuals, worse odour identification has also been linked to markers of brain pathology, such as increased cortical amyloid and thinner entorhinal cortex. These data imply that changes in olfactory function in cognitively normal individuals could thus represent preclinical neurodegenerative disease. [Neurology 2015;84:2153-2160; Front Psychol 2014;5:20]