Dazed & Confused

by Women's Brain Health Initiative:It is common for women to experience cognitive difficulties, sometimes referred to as “brain fog,” as they go through the menopause transition. They might be forgetful, or have trouble concentrating or thinking clearly. In one study, approximately 62% of midlife women self-reported an undesirable change in memory.Objective measurements of cognitive function (i.e. using standardized neuropsychological tests) have shown that women’s perceptions are accurate.Perimenopausal women do appear to experience a downward shift in some aspects of cognitive function, demonstrated by poorer performance on neuropsychological tests, compared to premenopausal and postmenopausal women.In one longitudinal research study conducted by Dr. Gail Greendale and colleagues, over 2,300 participants from the U.S. Study of Women’s Health Across the Nation (SWAN) completed multiple cognitive tests over a four-year period. Consistent with transitioning women’s perceived memory difficulties, perimenopause was associated with a subtle reduction in cognitive performance, characterized by an absence of a learning effect with repeated testing. This effect, however, was only temporary, with the participants’ performance rebounding to premenopausal levels in postmenopause. These findings – published in the May 2009 issue of Neurology – suggest that cognitive difficulties during the menopause transition may be time-limited.In another large, longitudinal study conducted by Dr. C. Neill Epperson and colleagues, the researchers examined menopause effects on verbal memory in particular, using various endocrine, behavioural, and cognitive assessments. The researchers wanted to determine whether there was an objectively-measured decline in cognition during the natural menopause transition that exceeded what would be expected with normal aging.A total of 403 women who were enrolled in the Penn Ovarian Aging Study participated in this research, undergoing annual assessments over a 14-year period from pre- to postmenopause. The researchers discovered a decline in verbal memory performance during the natural menopause transition that was independent of the typical effects of aging.They observed an actual worsening of performance on the cognitive tests over time, not just a failure to demonstrate practice-associated improvements. The overall decline in verbal memory was modest, but sufficient to validate women’s self-reported experiences of memory decline during the menopause transition. These findings were published in the September 2013 issue of The Journal of Clinical Endocrinology & Metabolism.Potential Factors Influencing Menopausal Brain FogHistorically, women’s self-reported complaints about brain fog were often attributed to life stress commonly experienced during midlife, as opposed to actual changes in a woman’s body as a result of menopauseScientists have now demonstrated, though, that menopause plays a direct role in the cognitive deficits that women experience in their 40s and 50s. Although the factors contributing to menopause-associated alterations in cognitive function are not yet fully understood, there are two pathways thought to underlie these changes, independently or in combination: (1) direct effects of estrogen; and (2) symptoms associated with the menopause transition.Estrogen’s Potential Role Estrogen influences hippocampal and prefrontal cortex function, thereby affecting the cognitive functions associated with these brain regions, including verbal memory and executive function. A 2014 review of over 15 years of research found that, in women aged 60 years and older, higher estradiol levels were potentially associated with better memory performance across multiple domains. (This research was conducted by Dr. Lisa Boss and colleagues, and published in Western Journal of Nursing Research.)A logical hypothesis, therefore, might be that as estrogen levels lower during the menopause transition, women experience cognitive challenges.However, a predictable, linear relationship between estrogen levels and cognitive function has not been found. For starters, while all women experience declines in estrogen levels during the menopause transition, not all women experience menopause-related cognitive difficulties. Moreover, the 2009 research conducted by Dr. Greendale and colleagues found that cognitive function rebounded after a woman passed from perimenopause (when estrogen levels fluctuate significantly) into postmenopause (when estrogen levels are at their lowest).Potential Impact of Menopause SymptomsScientists have further hypothesized that symptoms commonly associated with the menopause transition, such as hot flashes, sleep disruption, and depression, may account, at least in part, for menopausal brain fog. The findings on this matter to date, however, have been inconsistent, perhaps because of differing research methodologies.Some research has found that menopause symptoms do not appear to account for perimenopausal declines in cognitive function. For example, a longitudinal study conducted by Dr. Greendale and colleagues – published in the 2010 issue of American Journal of Epidemiology – examined 1,903 midlife U.S. women over a period of six years and considered two questions: (1) whether menopause-associated symptoms were related to cognitive function; and (2) whether such symptoms were responsible for the negative effect of perimenopause on cognitive performance.The researchers investigated four common menopause-associated symptoms: depressive, anxiety, sleep disturbance, and vasomotor (e.g., night sweats and hot flashes). They found that although there was a link between depressive and anxiety symptoms and poorer cognitive performance, none of the four symptoms accounted for the temporary declines in memory, learning, and how fast the brain processes information during the menopause transition.One small-scale study of 29 women – conducted by Dr. Pauline Maki and colleagues, and published in 2008 in Menopause – found that subjectively-measured (i.e. self-reported) hot flashes did not predict verbal memory performance. However, the researchers discovered that when moderate-to-severe hot flashes were objectively measured using a portable monitoring device, they were, in fact, related to declines in verbal memory.“In this study, we had participants record the hot flashes they noticed in a diary while wearing a monitor at the same time,” explained Dr. Maki, a Professor of Psychiatry and Psychology at the University of Illinois at Chicago. “This research approach revealed a very interesting finding: that the women were experiencing quite a few more hot flashes than they were self-reporting. We discovered that on average, the women underreported the number of hot flashes they had by 43%.”“This study revealed that objective, but not subjective, hot flashes are indeed linked to poorer verbal memory in midlife women with moderate-to-severe vasomotor symptoms,” continued Dr. Maki. The data suggested that this relationship was primarily due to nighttime rather than daytime hot flashes. The researchers therefore thought that perhaps it was sleep disruption caused by hot flashes that was negatively affecting cognitive function. When they analyzed the results in a way that allowed them to isolate the effects of sleep duration and nighttime hot flashes, though, each of those variables independently contributed to impaired verbal memory.“This 2008 study suggested that interventions to address hot flashes might provide cognitive benefit to women who experience moderate-to-severe symptoms,” said Dr. Maki. “We tested that theory in a later study – published in Maturitas in 2016 – and demonstrated that cognition does rebound when hot flashes are treated.” What Might Explain the Postmenopause Bounce Back in Cognitive Performance?Research suggests that perimenopausal brain fog is usually not permanent, nor a sign of a more serious condition like dementia.  Although many women experience a subtle decline in cognitive performance compared to premenopause, their performance bounces back to premenopausal levels once they reach postmenopause.Interesting research involving brain scans has provided some insight into what is occurring in a woman’s brain as she progresses through the various stages of menopause. “Women’s brains appear to adapt as they progress through the menopause transition. Their brain circuitry actually changes,” explained Dr. Maki.“Neuroimaging studies have shown that during pre- and perimenopause, the left side of the brain is primarily engaged to accomplish memory tasks. Postmenopausal women use both sides of the brain, though. It seems that the lower the estrogen levels, the more the two hemispheres of the brain are functionally connected.”“There is still a lot more to learn about cognitive function during the menopause transition,” continued Dr. Maki, “but women can take heart in the findings to date that indicate memory function appears to be most affected – and in only a subtle way – during perimenopause, but then rebounds.”Source: MIND OVER MATTER V8