Alzheimer’s disease (AD) is a common memory-impairment disorder frequently accompanied by olfactory identification (OI) impairments. In fact, OI is a valuable marker for distinguishing AD from normal age-related cognitive impairment and may predict the risk of mild cognitive impairment (MCI)-to-AD transition. However, current olfactory tests were developed based on Western social and cultural conditions, and are not very suitable for Chinese patients. Moreover, the neural substrate of OI in AD is still unknown. The present study investigated the utility of a newly developed Chinese smell identification test (CSIT) for OI assessment in Chinese AD and MCI patients. We then performed a correlation analysis of gray matter volume (GMV) at the voxel and region-of-interest (ROI) levels to reveal the neural substrates of OI in AD. Thirty-seven AD, 27 MCI, and 30 normal controls (NCs) completed the CSIT and MRI scans. Patients (combined AD plus MCI) scored significantly lower on the CSIT compared to NCs [ F (2,91) = 62.597, p < 0.001)]. Voxel-level GMV analysis revealed strong relationships between CSIT score and volumes of the left precentral gyrus and left inferior frontal gyrus (L-IFG). In addition, ROI-level GMV analysis revealed associations between CSIT score and left amygdala volumes. Our results suggest the following: (1) OI, as measured by the CSIT, is impaired in AD and MCI patients compared with healthy controls in the Chinese population; (2) the severity of OI dysfunction can distinguish patients with cognitive impairment from controls and AD from MCI patients; and (3) the left-precentral cortex and L-IFG may be involved in the processing of olfactory cues.

Background: Alzheimer’s disease (AD) manifests differently in males and females. However, the neuro-mechanism and influence factors are still unknown.Objective: To explore sex differences in brain network topology during AD disease progression and its association with cognition and possible influencing factors.Methods: Resting-state functional magnetic resonance imaging (MRI) data and cognitive scores were collected from 82 AD patients (50 females), 56 amnestic mildly cognitive impaired patients (29 females), and 63 healthy controls (38 females). Global and regional topological network metrics and modular architecture were calculated. Two-way ANOVA was performed to explore group and sex interactions and their main effects. Mediation analysis was used to explore the relationship among education, inter/intra-network connectivity, and the Mini-Mental State Examination (MMSE) score.Results: Lower levels of education, lower MMSE scores, and a positive correlation between the level of education and MMSE scores were found in female AD patients (p = 0.024, r = 0.319). Significantly lower connectivity strength within the sensorimotor network, dorsal attention network, ventral attention network (VAN), and between the sensorimotor and VAN were observed in male AD patients (p = 0.006, 0.028, 0.046, and 0.013, respectively). Group and sex interactions were also found in nodal properties, mainly in the frontal lobe, temporal lobe, middle cingulum, precuneus, and postcentral gyrus. Several of the altered brain network properties were associated with cognitive behavior in male AD patients. Education regulated the MMSE score through the mediation of connection strength between the default mode and limbic networks (LN) in the patient group (aMCI and AD combined).Conclusion: Our results demonstrate that sex differences exist at the brain network level in AD. Sex differences in network topology and education are correlated with sex differences in cognition during AD progression.

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Background The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals. Methods Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses. Results In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups. Conclusions Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.