University of Waterloo: Mariam Malik and Her Insights #4
- ForgetMeNotIntl
- Nov 27
- 4 min read
Hi everyone! I’m Mariam Malik and I am a recent graduate from the University of Waterloo, with Bachelor’s in Honours Health Sciences and Diploma in Gerontology. I am hoping to become a researcher either in health statistics or aging research. In my free time, I love reading and listening to audiobooks and I am always looking for recommendations!
Reviewed Article: Sex difference in brain functional connectivity of hippocampus in Alzheimer’s disease by Williamson et al.
Main Argument & Findings:
The National Institute of Health (NIH) has estimated that the prevalence of Alzheimer’s disease (AD) in the US is 6.5 million, and is projected to more than double by 2060. AD is the most common form of dementia and is currently the fifth leading cause of death for those older than 65. In addition to these rising numbers, the cost of caring for individuals with AD in their last 5 years is approximately $290,000, excluding indirect care costs. Therefore, there is a dire need for researchers to develop treatments and fully understand the pathology of AD. Numerous studies have concluded that AD is characterized primarily by the presence of amyloid-beta plaques (proteins that clump together to form plaques that disrupt cell function) and neurofibrillary tangles (abnormal accumulations of a protein called tau found inside neurons). Multiple clinical trials are attempting to target at least one of these pathological markers in an attempt to reduce AD prevalence.
Although the prevalence of AD is increasing, the distribution of AD between sexes is growing at different rates. The prevalence of AD in females is two-thirds higher than in men. Studies have found that women with AD perform worse on neuropsychological tasks and have greater total brain atrophy and temporal lobe degradation than men. Even among individuals without a dementia diagnosis, women with elevated amyloid-beta protein levels showed greater cognitive decline than men with the same levels.
There are numerous theories as to why this sex difference exists, including sex-specific hormones and genetics, menopause in women and hypertensive disorders during pregnancy. However, the authors focused on whether one of the brain regions affected earliest in AD shows sex-specific differences.
The hippocampus is located under the medial temporal lobe and is primarily responsible for learning and memory. In addition, it is among the first brain regions affected by AD. Studies have shown that the hippocampus and the entorhinal cortex (a region in the brain that serves as a pathway for relaying object and spatial information to the hippocampus) begin to atrophy in the early stages of AD. Individuals without dementia but with mild cognitive impairment also have hippocampal atrophy. However, studies have also found that hippocampal atrophy is significantly faster and affects the progression of AD only in females. The same authors recently found that connectivity from the hippocampus to other brain regions was significantly stronger in males with mild cognitive impairment than in females with mild cognitive impairment. This study aimed to determine whether there are sex differences in hippocampal connectivity in males and females with and without AD. The authors analyzed magnetic resonance imaging (MRI) and positron emission tomography (PET) scans of male and female subjects and measured connections between the hippocampus (left and right) and the rest of the brain.
In females with AD, the changes in hippocampal connectivity were more concentrated within the hippocampus itself. For example, up to 53% of the left hippocampus showed significant connectivity changes, whereas connectivity outside the hippocampus remained limited. This suggests that AD disrupts the memory circuits more directly in females. Males with AD showed a more widespread pattern of disruption. In one comparison, up to 76% of the right hippocampus showed altered connectivity, and these changes extended broadly into surrounding brain regions. This indicates that the disease spreads across a larger network in males than in a single area. An interesting finding is that even healthy men and women (those without AD) differed: males showed more distributed hippocampal connections while females showed more tightly focused patterns. This baseline difference may help explain why AD progresses differently across the sexes. Overall, males show a more widespread weakening across the system, while females show a more localized collapse.
These findings help clarify AD pathology and may inform earlier and targeted interventions. Still, some studies report no sex differences in hippocampal degradation in fully developed AD. More research is needed to determine whether these results are widespread or study-specific.
Importance for Youth:
This information is important for youth because the sex differences in AD highlight gaps in how the condition develops and affects individuals before symptoms appear. Understanding that women and men show different patterns in brain changes can help explain why some groups may be more vulnerable. Understanding this information encourages informed discussions, advocacy for inclusive research and a better understanding of why early detection and tailored interventions matter.
What I Learned:Â
Overall, I learned that AD does not affect the brain uniformly and its progression differs by sex. This notion reinforced how biological sex can influence disease pathways, treatment responses and potential risk. In addition, these findings push research and healthcare systems to avoid one-size-fits-all solutions. For example, if trials don’t account for sex-specific brain changes, treatments may be less effective for half the population. Ultimately, this highlights the need for more tailored diagnostics and interventions in healthcare.
Citations: Williamson, J., James, S. A., Mukli, P., Yabluchanskiy, A., Wu, D. H., Sonntag, W., ... & Yang, Y. (2023). Sex difference in brain functional connectivity of hippocampus in Alzheimer’s disease. GeroScience, 46, 563-572. https://doi.org/10.1007/s11357-023-00943-x