Sex Difference in Network Topology and Education Correlated With Sex Difference in Cognition During the Disease Process of Alzheimer

Abstract

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.

Global cognitive function is associated with sex, educational level, occupation type, and speech recognition rate in older Chinese adults: a single-center, prospective, cross-sectional study

“…This result complements that of a report by the Lancet Commission [5]. However, only a few studies [51,52] have demonstrated the presence of sex differences in MCI. Better attention and calculation performance in men than in women could arise from the effect of estrogen [53] or sex-specific cognitive reserve [5].…”

“…The brain atrophy rate of female patients with MCI is reportedly higher than that of male patients, with an additional decrease of 1.0-1.5% per year [56]. A possible explanation is that men may have higher resilience to MCI-related pathological damage to the brain [51] and better executive function than women; this finding is supported by cognitive reserve theory. However, this is different from the results of a previous study [57].…”

Longitudinal regression of covariance matrix outcomes

“…In a study comparing amnestic MCI and AD with healthy controls, a difference in right caudate nucleus atrophy was observed in females only. Alterations of functional connectivity in the somato-motor, dorsal, and ventral attention networks were identified in male patients (Li et al, 2021). In summary, our findings are in line with existing knowledge about AD.…”

Menopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer's disease

“…[1][2][3] Evidence clearly indicates that there is an increased age-independent prevalence of Alzheimer's disease (AD) in women compared to men (average odds ratio is 1.6) and that it is consistent with sexual dimorphism in AD pathophysiology, spanning molecular pathways of brain proteinopathies, neurodegeneration, neuroinflammation, and large-scale high-order organization of the brain. [4][5][6][7][8][9][10][11][12] In addition, women who experience early menopause, either naturally or iatrogenic, represent the highest risk cluster within the menopause population of late-life cognitive decline and dementia. 13,14 The higher vulnerability of perimenopausal (transition phase) and early-menopause women than men has been established by large-scale neuropsychological studies, post-mortem investigations, biomarkerbased studies, data-driven multi-variate analysis, and experimental models of aging and AD.…”