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.

BackgroundMajor depressive disorder (MDD) is a common psychiatric disease and a leading cause of disability worldwide. Handgrip strength (HGS) as an objective physical fitness test is a practical index for identifying many diseases. Previous studies drew different conclusions about the relationship between HGS and MDD.AimsWe aim to explore whether HGS has an effect on the risk of MDD.MethodsHGS-related single-nucleotide polymorphisms identified by a genome-wide association study were used as instrumental variables in this Mendelian randomisation (MR) study. Summary data on MDD were obtained from the Psychiatric Genomics Consortium. Four methods were applied, including inverse variance weighted (IVW), MR Egger, weighted median and weighted mode. Additional sensitivity analyses, including leave-one-out, heterogeneity test, pleiotropy test and confounders identification, were conducted to test the robustness of our results.ResultsEach 1 kg increase in left HGS is associated with a 21.95% reduction in the risk of MDD (ORIVW = 0.781, 95% CI: 0.650 to 0.937, p=0.009), while no significant correlation exists in the estimation of right HGS (p=0.146). Sensitivity analyses demonstrated statistical significance (βIVW = −0.195, p=0.023) after excluding some genetic loci that cause pleiotropy.ConclusionsIncreased left HGS is associated with a reduced risk of MDD. In the future, it may be used as an index for the clinical screening, observation and treatment of MDD.