Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults

Abstract

Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin' Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.

Characteristic early changes of Glu and Cho in brain regions affected by different types of subjective cognitive decline and their clinical significance

“…Therefore, the main clinical manifestation is non memory dysfunction, such as execution, computation, etc. [28,29] In summary, there are changes in the concentration levels of biochemical metabolites in the hippocampus on both sides of VCIND patients. 1 H-MRS can sensitively detect abnormal metabolic changes in the brain of VCIND patients, which is helpful for early diagnosis and disease monitoring.…”

Olfactory function, neurofilament light chain, and cognitive trajectory: A 12‐year follow‐up of the Shanghai Aging Study

“…A previous cross-sectional study examined the associations of OD with plasma Aβ42, Aβ40, the Aβ42/Aβ40 ratio, ttau, and NfL, and found significant results with only t-tau and NfL. 18 Whether AD pathology plays a role in the relationship of OD and cognitive deterioration deserves further investigation. Fifth, we did not take Parkinson's disease (PD) or α-synuclein pathology into consideration when analyzing the relationship of OD, NfL, and cognitive decline.…”

“…Faster olfactory decline could predict smaller olfaction‐ and AD‐associated brain regions 9 . Of note, one cross‐sectional study measured plasma t‐tau and NfL in 1054 participants and found a linear relationship between olfactory impairment and higher levels of t‐tau and NfL 18 . However, thus far, few studies have tried to disentangle the relationships among olfaction, neurodegeneration, and cognition.…”

“…9 Of note, one cross-sectional study measured plasma t-tau and NfL in 1054 participants and found a linear relationship between olfactory impairment and higher levels of t-tau and NfL. 18 However, thus far, few studies have tried to disentangle the relationships among olfaction, neurodegeneration, and cognition. Reijs et al did not find that CSF t-tau modified the association between olfaction and cognitive function.…”

“…21 One cross-sectional study found that higher plasma NfL was associated with anosmia. 18 Longitudinal studies exploring the interactive effect of blood NfL and olfactory function with cognitive impairment are still lacking.…”