Association of anosmia with mild cognitive impairment and biomarkers of brain aging

Abstract Background Olfactory impairment has been associated with neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease (AD). We seek to investigate the relationships of impaired olfaction with mild cognitive impairment (MCI), plasma biomarkers of AD and neurodegeneration, and neuroimaging markers of microvascular lesions and neurodegeneration among Chinese older adults. Method This population‐based cross‐sectional study included 4214 participants (age ≥65 years; 56.0% women) from MIND‐China who were free of dementia and examined in March‐September 2018. Olfactory function was assessed using the 16‐item Sniffin’ Sticks identification test (SSIT). In the subsamples, we measured plasma concentrations of amyloid‐β40 (Aβ40), Aβ42, total‐tau, and neurofilament light chain (NfL) using the Simoa technology (n = 1054); and quantified hippocampal volume, entorhinal cortex volume, Alzheimer’s disease‐signature cortical thickness, and white matter hyperintensities (WMHs) volume on MRI scans (n = 917). The neuropsychological test battery was used to assess memory, verbal fluence, attention, and executive function. MCI and subtypes of MCI were defined according to the Petersen’s criteria that integrated clinical judgement by neurologists and neuropsychological tests. Data were analyzed with logistic and general linear regression models. Result Of the 4214 participants, MCI was diagnosed in 1102 persons (26.2%), including 931 with amnestic MCI (aMCI) and 171 with non‐amnestic MCI (naMCI). Olfactory impairment (SSIT score 0‐10) was associated with an increased likelihood of MCI, aMCI, and naMCI in a dose‐response manner (p for trend<.001). In the plasma biomarker or MRI subsample, anosmia (SSIT score 0‐7) was significantly associated with plasma total‐tau (demographic‐adjusted β = 0.26; 95% CI = 0.12‐0.41), NfL (0.12; 0.04‐0.19) and MRI biomarkers of hippocampal volume (‐0.13; ‐0.22‐ ‐0.04), entorhinal cortex volume (‐0.08; ‐0.13‐ ‐0.02), and WMHs volume (0.19; 0.08‐0.30), and marginally associated with Alzheimer‐signature cortical thickness (‐0.02; ‐0.05‐0.00, p = 0.08), but not with plasma Aβ concentrations (P>0.05). Conclusion Anosmia may be a clinical marker for preclinical dementia and neurodegeneration among older adults. Microvascular and neurodegenerative lesions in the brain may be the common neuropathological pathways linking anosmia with cognitive impairment.