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. 2022 Aug 10:14:959394.
doi: 10.3389/fnagi.2022.959394. eCollection 2022.

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

Jordan Williamson  1 , Andriy Yabluchanskiy  2 , Peter Mukli  2 , Dee H Wu  3   4   5   6 , William Sonntag  2 , Carrie Ciro  7 , Yuan Yang  1   4   7   8   9
Affiliations

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

Jordan Williamson et al. Front Aging Neurosci. .

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.

Keywords: Alzheimer’s disease; functional connectivity; hippocampus; mild cognitive impairment; sex difference.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Sex-Specific Pathological Features with Right Hippocampus as ROI. Highlighted display the statistically significant cortical regions between mild cognitive impairment (MCI) and cognitively normal (CN) (p < 0.001) normalized to a 1–10 scale. Orange arrows indicate the areas of difference at the precuneus cortex. Panels (A–C) display MMCI v MCN. Panels (D–F) display FMCI v FCN.
FIGURE 2
FIGURE 2
Sex-Specific Pathological Features with Left Hippocampus as ROI. Highlighted areas display the statistically significant cortical regions between mild cognitive impairment (MCI) and cognitively normal (CN) (p < 0.001) normalized to a 1–10 scale. Orange arrows indicate the area of difference at the precuneus cortex. Panels (A–C) display MMCI v MCN. Panels (D–F) display FMCI v FCN.
FIGURE 3
FIGURE 3
Sex-Specific Pathological Features Sagittal View. Highlighted Areas display the statistically significant regions between cognitively normal (CN) and mild cognitive impairment (MCI) (p < 0.001) normalized to a 1–10 scale. Orange circles indicate the area of difference in the brain stem and provide size reference between subplots. (A) Right Hippocampus ROI MMCI v MCN. (B) Left Hippocampus ROI MMCI v MCN. (C) Right Hippocampus ROI FMCI v FCN. (D) Left Hippocampus ROI FMCI v FCN.
See this image and copyright information in PMC

References

    1. Alzheimer’s Association (2016). 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 12 459–509. 10.1016/j.jalz.2016.03.001 - DOI - PubMed
    1. Andrew M. K., Tierney M. C. (2018). The puzzle of sex, gender and Alzheimer’s disease: Why are women more often affected than men? Womens Health 14:1745506518817995. 10.1177/1745506518817995 - DOI
    1. Braak H., Braak E. (1995). Staging of Alzheimer’s disease- related neurofibrillary changes. Neurobiol. Aging. 16 271–278. 10.1016/0197-4580(95)00021-6 - DOI - PubMed
    1. Burke S. L., Tianyan H., Fava N. M., Li T., Rodriguez M. J., Schuldiner K. L., et al. (2019). Sex differences in the development of mild cognitive impairment and probable Alzheimer’s disease as predicted by the hippocampal volume or white matter hyperintensities. J. Women Aging 31 140–164. 10.1080/08952841.2018.1419476 - DOI - PMC - PubMed
    1. Cavanna A. E., Trimble M. R. (2006). The precuneus: A review of its functional anatomy and behavioral correlates. Brain 129 564–583. 10.1093/brain/awl004 - DOI - PubMed

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