Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer’s Disease

Abstract

Background Odor identification (OI) dysfunction is an early marker of Alzheimer’s disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. Methods Two hundred and sixty-nine subjects were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were compared to explore the changing pattern of structural and functional abnormalities across AD, MCI, SCD and normal controls. Results From the SCD, MCI to AD groups, the reduced GMV, increased ALFF, increased ReHo and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. In particular, SCD subjects exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus) and reduced FC (hippocampus- hippocampus and hippocampus-parahippocampus ) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all subjects. Conclusion Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.

Properties of odor identification testing in screening for early-stage Alzheimer’s disease

“…However, age, sex, and education did not significantly predict odor identification scores in the linear regression models. These findings are in accordance with structural and functional changes in the olfactory system, which have been demonstrated in previous studies, and further prove that olfactory impairment is associated with processes of AD itself and cannot be explained by other factors that have been proven to influence olfaction in the general population, such as age and sex [24][25][26][27][28][29] . As olfactory and memory systems are known to significantly overlap anatomically and both are affected by cholinergic deficit, present in AD, the relationship between olfactory and cognitive impairment might be related pathogenetically.…”

“…Structures involved in the processing of olfactory information (especially entorhinal and transentorhinal areas) are affected by AD pathology early in the course of the disease 24,25 . Functional magnetic resonance imaging (fMRI) and [18F]-fluorodeoxyglucose PET (FDG-PET) also confirmed structural and functional abnormalities of olfaction-related regions in AD patients as early as SCD [26][27][28][29] .…”

Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline

“…The hippocampus plays a critical role in cognition ( Lisman et al, 2017 ). A previous study found that SCD exhibits a consistent pattern of hippocampal atrophy ( Chen et al, 2021 ). Some studies have observed a decreased hippocampal volume in individuals with SCD both at baseline and during a significant longitudinal decline ( Scheef et al, 2012 ; Sánchez-Benavides et al, 2018 ; van Rooden et al, 2018 ; Yue et al, 2018 ), with an annual decrease of 1.9% ( Cherbuin et al, 2015 ; Wang et al, 2020 ).…”

Uncovering the Correlation between COVID-19 and Neurodegenerative Processes: Toward a New Approach Based on EEG Entropic Analysis

“…One intriguing aspect identified in the literature is that both SARS-CoV-2 infections and neurodegenerative diseases [ 30 , 31 ] (AD in particular) may lead to an impairment of the olfactory system. Anosmia, the loss of sense of smell, is one of the first and most frequent symptoms of COVID-19, and an estimated 85% to 98% of patients experience some degree of olfactory dysfunction [ 32 ].…”