Abstract
Odor identification ability may serve as an important diagnostic biomarker in Alzheimer’s disease (AD). The aim of the study is to investigate the contribution of A/T/N neuroimaging biomarkers to impaired odor identification ability in the Alzheimer’s disease spectrum. In 127 participants, we compared A/T/N neuroimaging biomarkers between normosmia and hyposmia groups, and performed correlation analysis between the biomarkers and Cross-Cultural Smell Identification Test (CCSIT) scores. Additionally, path analysis for odor identification ability was performed using cognitive function as a mediator. In between-group comparison, individuals with hyposmia showed higher frequency of amyloid-β (Aβ) positivity, and lower neuropsychological test performance than those with normosmia. After correction for covariates including total cognition scores, there was no difference in the Aβ or tau burden between the normosmia and hyposmia groups, and no correlation between CCSIT scores and Aβ or tau burden. Meanwhile, cortical volumes in the lateral and medial temporal cortices were smaller in the hyposmia group and decreased with the worsening of CCSIT scores. Path analysis showed that only neurodegeneration had a direct effect on odor identification, while Aβ and tau burden contributed to odor identification with the mediation of cognition. In the Alzheimer’s disease spectrum, impaired odor identification ability may be attributable to neurodegeneration rather than the direct effect of Aβ or tau burden.
Highlights
Odor identification ability may serve as an important diagnostic biomarker in Alzheimer’s disease (AD)
We found that the hyposmia group exhibited smaller volume in the entorhinal cortex than the normosmia group
Previous positron emission tomography (PET) imaging studies have shown a higher negative predictive value of odor identification ability on Aβ burden in the elderly, suggesting that individuals with preserved odor identification ability are less likely to have Aβ d eposit[9,10]. Another PET study showed a correlation between odor identification ability and regional Aβ burden in the posterior cingulate, temporoparietal, and lingual cortices in mild cognitive impairment (MCI) and AD p atients[22]
Summary
Odor identification ability may serve as an important diagnostic biomarker in Alzheimer’s disease (AD). Impaired odor identification has been associated with the CSF biomarker for neurodegeneration[11] and volume atrophy in the medial temporal cortex[12,13] where tau pathology appears early in AD14. In these A/T/N biomarkers, there is no information regarding which biomarker has the greatest effect on odor identification. The brain regions related to the central olfactory pathway, such as the entorhinal cortex, amygdala, and hippocampus overlap with the regions most vulnerable to pathological changes in AD19–21 It remains unclear whether AD pathology directly effects odor identification ability, or if it is mediated by cognitive dysfunction. We investigated whether cognitive dysfunction mediates the association between the biomarkers and impaired odor identification
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