New study explores impact of biological sex affects brain aging and memory function

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Dr. Natasha Rajah

Source: Douglas Mental Health University Institute

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. In the current task fMRI study, researchers tested the hypothesis that there are sex differences in the effect of age and memory performance on brain activity during episodic encoding and retrieval of face—location associations (spatial context memory).  The results of the study were published in the Journal of Cognitive Neuroscience by Ms. Sivaniya Subramaniapillai, a Ph.D. candidate in Dr. Maria Natasha Rajah’s lab.

Dr. M. Natasha Rajah, senior author on the study, received her Ph.D. in Experimental Psychology from the University of Toronto in 2003 and did her post-doctoral training at U.C. Berkeley (2003–2005). She joined the Douglas Institute in 2005 when she took on the role of Assistant Professor at the Department of Psychiatry at McGill University. Dr. Rajah’s research is focused on the cognitive neuroscience of memory and aging. In 2007, she was awarded a prestigious CIHR New Investigator Salary Award. She then went on to receive a FRQ-S Junior 2 Research Scholar Award. In 2009 she was promoted to Associate Professor. In 2011, Dr. Rajah became the Director of the Douglas Brain Imaging Centre. She was named one of the top 50 scientists in Quebec under 50 yrs of age in 2012 by Quebec Science magazine. She was awarded the Mentorship award by Women in Cognitive Science Canada & the Haile T. Debas Prise by McGill University in 2019. She is currently a Full Professor with tenure and Director of the Douglas BIC.

Dr. Rajah took the time to answer some of our questions about this recent study.

What can the results of your research add to scientific research?

Alzheimer’s disease (AD) affects one’s ability to learn and remember details about past experiences, a phenomenon that is referred to as episodic memory. Indeed, episodic memory is one of the earliest and most pronounced deficits experienced in AD, and significantly affects one’s quality of life and safety. There is evidence that dysfunction in the brain networks, important for episodic memory, arises decades prior to the onset of AD, and that these dysfunctions may be present at subclinical levels in cognitively healthy adults. In addition, there is evidence that women may be at greater risk for late-onset Alzheimer’s disease, compared to men.

However, no study in the past has directly examined whether there are sex/gender differences in the effect of age on memory-systems vulnerable to AD pathology, i.e. episodic memory. It is critical to develop a working model of healthy aging in both sexes to better understand why there are sex differences in the prevalence of specific age-related diseases (i.e. AD) and how treatment interventions should be tailored in the realm of aging and dementia. Therefore, the goal of this study was to address this important issue as directly test for similarities and differences in how age affects memory-related brain function in women, compared to men, across the adult lifespan.

According to your studies and the results of your research, what are the gender distinctions related to memory performance?

Our results indicate that behaviourally there were no sex differences in memory performance. Both sexes performed the same on the memory task and there was significant age-related memory decline observed in both women and men.

Our functional magnetic resonance imaging or functional MRI (fMRI) (test which measures brain activity by detecting changes associated with blood flow) results indicate that both sexes, on average and across age, showed similar brain activation patterns during learning (or encoding) of episodic memories. However, there were sex differences in the brain regions activated during successful remembering—suggesting women and men may use different neural retrieval strategies.  Women engaged frontal parietal and medial temporal systems to encoding and retrieve memories successfully. Men engaged these same systems at encoding but activated different brain regions, important for semantic processing, during retrieval. These sex differences were related to performance but not age.

We also observed sex differences in the effect of age on memory-related brain function. Specifically, our study shows that the neural correlates of age-related memory decline differs in women and men. Women exhibited age-related deficits in right frontal and midline cortical regions—brain regions that exhibit dysfunction in early AD. Therefore, this is the first findings to link neural signatures of AD pathology (dysfunction in midline cortical regions) to age effects in women, not men. This suggests that this neural signature of AD risk may be sex-specific. In contrast, men exhibited age-related declines in the lateral networks of the semantic memory (memory of facts, ideas, meaning and concepts), which they engaged to support retrieval. Moreover, we found evidence that women exhibited age-related compensation in frontal-parietal cortex, which directly correlated with better subsequent memory. Taken together, our findings show that biological sex affects brain aging and memory function, and indicate that any given treatment related to memory functions in healthy and pathological aging should be tailored to treat each sex uniquely.

In light of your results, what do you think are the major challenges for scientific research?

Given the negative health outcomes suffered by women due to the medical and pharmaceutical fields’ exclusionary practice of primarily studying males/men in their research project, it is clear that we need to consider sex in biomedical and clinical health research.  Our current study highlights how consideration of sex in research design and analysis can advance our understanding of the possible sex differences in the biological systems mediating behavioural performance, even when there are no sex differences in behavioural performance per se. By understanding these sex differences, we are better equipped to develop targeted, personalized interventions that support brain health and healthy aging in our society.

November 21, 2019

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