World Alzheimer’s Day

By Paula Duarte-Guterman and Liisa Galea

Alzheimer’s Disease is a degenerative disease that results in cognitive decline, a progressive loss of brain cells, and the addition of pathological features in the brain. One of the areas first affected by Alzheimer’s Disease is the hippocampus, a brain area important for the formation of new memories. Women are disproportionately affected by Alzheimer’s Disease compared to men, with two-thirds of Alzheimer’s Disease patients being women, although this demographic may be changing with recent studies indicating that the sex disparity is more evident in European compared to North American populations. More importantly, women with Alzheimer’s Disease also show greater neuropathology and cognitive decline than men with Alzheimer’s Disease and women caregivers share a greater burden care than men caregivers. Women’s health researchers in this area are interested in understanding why Alzheimer’s Disease impacts women more so than men. They investigate how unique female experiences such as pregnancy, motherhood, and menopause may be important for brain health and disease. There is increasing evidence that women are more likely to develop Alzheimer’s Disease when they have a previous history of multiple pregnancies. In addition, hormone levels decline around menopause and this has been proposed as an important factor in cognitive decline with aging and developing Alzheimer’s Disease. Certain hormone therapies have been associated with a reduced risk of Alzheimer’s Disease but unfortunately, this research is controversial as some studies have not found any beneficial effects of hormone therapies.

Work at UBC, with WHRI members, is exploring the effects of estrogens and reproductive experience (motherhood) on the hippocampus, the brain area that is implicated in Alzheimer’s Disease. For example, estrogens increase the production of new neurons in the hippocampus in females with a history of past pregnancies but not in females with no history of pregnancies. In their latest work, Liisa Galea and her team tested the idea whether hormone therapy would have different effects on cognition and brain function in females depending on their reproductive history. In middle aged rats, Premarin (a very commonly prescribed hormone therapy for women) improved spatial memory and reduced inflammation in females that had never mothered before but Premarin had the opposite effect in females with history of one pregnancy. This work demonstrates that hormone therapies have different effects on cognition and brain function later in life depending on reproductive history. The laboratory is continuing to assess the long term impacts of pregnancy and motherhood on the brain in both animal models and humans. Work by Teresa Liu-Ambrose indicates that women with mild cognitive impairment may have a greater benefit from physical activity on memory than men, and work is ongoing to determine what mechanisms may explain this greater benefit. These studies indicate why it is so important to fund and research the influence of Alzheimer’s Disease in both men and women to determine whether different treatments may be necessary between the sexes in order to afford the best treatments to offset this devastating disease. Research in this area will help determine what makes women more vulnerable to the impact of to Alzheimer’s Disease as they age and which treatments or combination of treatments (exercise and hormone therapies) might be beneficial depending on your reproductive history.

Relevant papers for further reading

  1. Galea LAM et al. Beyond sex differences: short and long-term implications of motherhood on women’s health. Curr Opin Physiol 06:82 (2018)
  2. Prince MJ et al. Reproductive period, endogenous estrogen exposure and dementia incidence among women in Latin America and China; A 10/66 population-based cohort study. PLoS ONE 13:e0192889 (2018)
  3. Jang H et al. Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease. Neurology 91:e643 (2018)
  4. Barha CK, Galea LAM. Motherhood alters the cellular response to estrogens in the hippocampus later in life Neurobiol Aging 32:2091 (2011)
  5. Galea LAM et al. Premarin has opposing effects on spatial learning, neural activation, and serum cytokine levels in middle-aged female rats depending on reproductive history. Neurobiol Aging 70:291 (2018)
  6. Barha CK et al. Sex difference in aerobic exercise efficacy to improve cognition in older adults with vascular cognitive impairment: secondary analysis of a randomized controlled trial. J Alzheimers Dis. 60:1397 (2017)