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Clearing the “Brain Fog” of Menopause

The symptomology can add insult to injury.

“It’s unfair,” a cousin complained. “I am up half the night with hot flashes, and I carry fans in my pockets so I won’t sweat during the day. My weight hasn’t really changed, but my fat cells seem to be sliding into pouches around my middle and my hips. And now I am seriously suffering from brain fog. I can’t remember anything. When my mother was given a memory test to see if she was developing Alzheimer’s, I tried remembering the words and the story on the tests the neurologist was giving her, and I couldn’t.“

The other older female relatives hearing her tale of woe nodded in recognition. “It’s the change,” said the oldest. “Menopause. We went through all that as well.” And the stories began of forgetfulness, difficulty in processing information, inability to multi-task and for some, unexpected depression and anxiety.

“What did your doctor say?” asked a younger cousin, no doubt worrying about what would happen to her in a few years. “Not much,” was the answer, “except that I could try hormones for a short time to see if it would help, but then I couldn’t because there is breast cancer in my family.”

Menopause occurs when the ovaries stop functioning and estrogen levels drop significantly. Unless the ovaries are removed as part of a surgical procedure, the decrease and final cessation of ovarian function can occur over a period of several years—4 to 10, according to a review article in JAMA.

During the early stage, there is considerable variability in the frequency and duration of the menstrual cycle, while the late stage is characterized by the absence of a menstrual cycle for at least 60 days. This period of transition from reproductive capacity to its permanent absence is also known as perimenopause.

The physical, cognitive, and mood changes of menopause are well known and may last several years. A study cited in the JAMA article traces the cognitive changes of about 200 women as they transition from pre-menopause through perimenopause. They were tested on various aspects of cognitive function and showed a measurable decrement in their memory.

For example, they were asked to remember the contents of a short paragraph right after it was read to them, and then several minutes later. Their memory was diminished compared to their performance before perimenopause.

In another study, women had difficulty retrieving words, lost their train of thought easily, were forgetful about appointments, and often could not remember the purpose of a particular behavior (like entering a room to get keys).

The authors point out that menopausal forgetfulness and poor cognitive performance are rarely severe enough to affect the ability to function (although the “find my phone” app on cell phones may be essential). Nor is it clear whether any of the deficits will persist post-menopause. Although these authors do not offer any specific interventions to reverse these deficits, there is evidence from a four-year study of women from the ages of 42-52, that repeated practice on tests of cognitive function could improve performance during the early and middle years of perimenopause.

Women going through the menopause transition commonly experience vasomotor symptoms, i.e., hot flashes or night sweats leading to sleep disturbances. Symptoms of depression and anxiety also may appear during these years. Even though it is known that memory, attention, word retrieval, and other cognitive functions can be affected by lack of sleep or mood changes, studies have shown that the perimenopausal cognitive changes occur independently of changes in sleep or mood.

What seems to be producing the forgetfulness and other symptoms of cognitive decline (albeit temporary) is an interaction between the decline in estrogen levels as the woman goes through perimenopause and serotonin activity in the brain. There have been animal and human studies suggesting that estrogen may affect both mood and cognition through its effect on serotonin.

In one study, women were given a diet that reduced the level of tryptophan in their brain, the amino acid that makes serotonin, and as a result, they demonstrated a decrease in memory. Studies are ongoing to see whether early intervention with hormones may lessen cognitive impairment; however, there is no consensus on its effectiveness.

Avoiding menopause is not possible, but not everyone experiences its symptoms. That is the good news. The bad news is that having suffered from the mood swings of PMS, especially depression, a woman is more likely to experience similar mood changes as she makes her way through the perimenopausal years.

Cognitive changes are also extremely common during the last several days of the menstrual cycle. Women ‘s scores on measurements of attention and concentration, verbal and visual memory, working memory, and reaction time are lower at the end of the menstrual cycle, compared to their scores at the beginning of the cycle.

Might the cognitive difficulties associated with PMS also be a harbinger of problems later on during menopause? The probability is there because serotonin activity seems to be compromised during the days of the menstrual cycle when estrogen levels are lower. Studies we carried out at MIT many years ago with women who had consistently moderate to severe PMS indicated a decrease in serotonin activity that could be restored by giving a drug that increased the activity of this neurotransmitter. Subsequently, when premenstrual women consumed sufficient carbohydrates to increase serotonin, their performance on cognitive tests was significantly better than when they consumed protein, which prevents serotonin synthesis.

Might increasing serotonin synthesis, and thus activity, also have an effect on the cognitive performance during the menopause transition? Would eating small amounts of carbohydrate, such as a cup of dry cereal, reduce “brain fog”? And would food plans that limit carbohydrates, like the keto diet, make the “fog” denser? These are questions that should be addressed.

References

“The Menopause Transition and Cognition,” Greendale G, Karlamangla A, Mai P, JAMA 2020; 323: 1495-1406.

Effects of the menopause transition and hormone use on cognitive performance in midlife women,” Greendale GA, Huang MH, Wight RG, et al., Neurology 2009; 72:1850–1857.

“Interactive effects of estrogen and serotonin on brain activation during working memory and affective processing in menopausal women,” (Epperson CN, Amin Z, Ruparel K, Gur R, Loughead J., Psychoneuroendocrinology. 2012; 37(3): 372‐382.

“Effect of estrogen-serotonin interactions on mood and cognition,” Amin Z, Canli T, Epperson CN, Behav Cogn Neurosci Rev. 2005; 4:43–58.

"Menopausal Symptoms and Their Management," Santoro N, Epperson C, Matthews S, Metab Clin North Am. 2015; 44(3): 497‐515.

“Premenstrual syndrome as a predictor of menopausal symptoms,” Freeman EW, Sammel MD, Rinaudo PJ, Sheng L., Obstet Gynecol. 2004; 103:960–966.

“Neuropsychological performance and menstrual cycle: a literature review,” Souza, Eliana Gonçalves V. et al,T rends Psychiatry Psychother. [online]. 2012; .34: 5-12.

“D-Fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression,” Brzezinski, A.A., Wurtman, J.J., Wurtman, R.J., Gleason, R., Greenfield, J., and Nader, T. Obstet. & Gynecol., 1990; 76:296-391.

“The effect of a carbohydrate-rich beverage on mood, appetite, and cognitive function in women with premenstrual syndrome,” Sayegh, R., Schiff, I., Wurtman, J., Spiers, P., McDermott, J., and Wurtman, R.J., Obstet. Gynecol., 1995; 86:520-528, 1995.

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