Sex differences in brain functional connectivity of hippocampus in mild cognitive impairment

Abstract

Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer’s Disease (AD). Prior research shows that females are more impacted by MCI than males. On average females have a greater incidence rate of any dementia and current evidence suggests that they suffer greater cognitive deterioration than males in the same disease stage. Recent research has linked these sex differences to neuroimaging markers of brain pathology, such as hippocampal volumes. Specifically, the rate of hippocampal atrophy affects the progression of AD in females more than males. This study was designed to extend our understanding of the sex-related differences in the brain of participants with MCI. Specifically, we investigated the difference in the hippocampal connectivity to different areas of the brain. The Resting State fMRI and T2 MRI of cognitively normal individuals (n = 40, female = 20) and individuals with MCI (n = 40, female = 20) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed using the Functional Connectivity Toolbox (CONN). Our results demonstrate that connectivity of hippocampus to the precuneus cortex and brain stem was significantly stronger in males than in females. These results improve our current understanding of the role of hippocampus-precuneus cortex and hippocampus-brainstem connectivity in sex differences in MCI. Understanding the contribution of impaired functional connectivity sex differences may aid in the development of sex specific precision medicine to manipulate hippocampal-precuneus cortex and hippocampal-brainstem connectivity to decrease the progression of MCI to AD.

Exploring the Influence of Gut–Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics

“…The development of Alzheimer's disease [69,[88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107] and the mechanisms through which the microbiome can contribute to the progression of Alzheimer's disease have been investigated . Numerous studies are also available regarding treatments with probiotics [139][140][141][142].…”

Western diet-induced obesity results in brain mitochondrial dysfunction in female Ossabaw swine

“…Due to its size, the pig brain also offers the possibility to isolate large amounts of mitochondria that ensures stability of respiratory parameters when isolating from distinct brain regions (Fišar and Hroudová, 2016), which may enhance the predictive value of this preclinical model (Perleberg et al, 2018). Additionally, this study focused on females, which have greater cognitive deterioration compared to males at the same stage of neurodegenerative disease (Cerri et al, 2019;Williamson et al, 2022). However, several limitations must be considered when interpreting the findings of the present study.…”

Cerebrovascular Dysfunction in Alzheimer’s Disease and Transgenic Rodent Models

“…Epidemiological studies have indicated that women have a higher prevalence of AD, with two-thirds of AD cases residing in women [241,242]. While the prevailing view attributes this discrepancy to women's longer average lifespan (4.5 years more than men) [243], other factors contribute.…”

“…While the prevailing view attributes this discrepancy to women's longer average lifespan (4.5 years more than men) [243], other factors contribute. These include: 1) women born in the 20 th century had lower education levels and incomes than men which contributes to an increasing number of dementia cases [243]; 2) men have a higher cardiovascular death rate in middle age, resulting in a lower rate of dementia in those that survive to an advanced age [243]; 3) women lose the neuro- [244] and vascular-protective [245] effects of sex hormones after menopause; 4) women's brains are more vulnerable to the effects of AD pathology and a weaker interhemispheric functional connectivity compared to men [241,242]. Despite the notable sex differences in the incidence of AD among humans (>3000 studies in 5 years), there has been a shortage of studies to determine the mechanisms involved.…”