Brain fog is common in midlife women and a stunning 40 to 60% of midlife women report cognitive changes during perimenopause. Symptoms of brain fog include forgetfulness; difficulty remembering words, names, anecdotes, and numbers; difficulty focusing and concentrating; and distractibility. [i] Some women may report symptoms that would best be evaluated for attention deficit hyperactivity disorder (ADHD). [ii] Whether it’s perimenopause/menopause brain fog or ADHD, if untreated, these symptoms can cause distress and anxiety and an unnecessary fear of pending dementia.
Healthcare providers can conduct testing to determine what aspects of one’s cognition is changing over time through menopause and beyond, and if ADHD is present. Some difficulties in cognition can be because of menopause symptoms including sleep disruption, depression, and anxiety. Studies find small declines in memory performance, within normal limits, as women enter perimenopause. [iii]
There is no clear research evidence about the duration of objective declines in cognition. However, subjective complaints do often persist from perimenopause into postmenopause. The duration and severity of cognitive issues can be influenced by hormone changes and by the severity and duration of other menopause symptoms. Cognitive changes are challenging to experience and challenging to assess by a healthcare provider because the course of changes varies widely.
Declines in blood levels of estradiol are normal with menopause and do contribute to these midlife cognitive difficulties. Women who have had their ovaries removed may have greater cognitive difficulties if they are not taking systemic estrogen. i Estrogen affects cognitive performance by influencing brain activities in regions that are rich in estrogen receptors. [iv] Vasomotor symptoms (VMS) are also associated with declines in memory, increased ischemic lesions in the brain, and Alzheimer’s disease biomarkers.[v] Again, sleep disturbances also play a role [vi], as do anxiety and depressive symptoms that can increase in severity in perimenopause, and these too may be linked to cognitive changes.
Systemic estrogen therapy alleviates vasomotor symptoms well, however, there are no large-scale clinical trials looking at the influence of menopause hormone therapy (MHT) on cognition in women with moderate to severe VMS.
As of this writing, four quality clinical trials that have studied the effect of MHT on cognitive performance in postmenopausal women were neutral, no benefit no harm, regardless of the time since their last menstrual period, or the formulation, type, or delivery of either the estrogen or the progestogen. In older postmenopausal women, conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) had a negative effect on cognition, but oral estradiol and vaginal progesterone had a neutral effect. [vii], [viii],[ix],[x]
In women who start systemic MHT in perimenopause, or within the first 10 years of menopause, or before age 60 , may have reduced Alzheimer’s disease, but women who start after age 60 or after 10 years since their last menstrual period, systemic MHT may actually increase their risk of Alzheimer’s disease.[xi] On the other hand, women who have had their ovaries removed prior to the average age of menopause of 52, and have not been on estrogen therapy until at least the age of 52, might have greater cognitive decline and risk of Alzheimer’s disease. [xii] Women who have premature ovarian insufficiency (menopause before age 40) or early menopause (last menstrual period between ages 40 and 45) will also likely have less cognitive decline if they take systemic MHT at least until age 52. It is very important to speak with a well-informed, up-to-date menopause practitioner to help determine the benefits and risks for brain fog and brain aging, as well as many other issues including cardiovascular disease, osteoporosis, breast cancer, and more. Systemic MHT is not an elixir of life or the next greatest super food as one might think if reading modern media posts from non experts. It is a very individualized assessment of benefits versus risks.
The duration of declines in cognitive performance is unclear, and again, vastly variable from woman to woman. The duration and severity of cognitive difficulties can be influenced by hormone changes and by the severity and duration of other menopause symptoms, but also includes education level, stress, physical health, medications, and other chronic health problems.
Midlife women with brain fog concerns can often be reassured that their changes are normal and typically improve. Brain health can be maintained, and Alzheimer’s dementia can be prevented or delayed with some key practices. A Mediterranean Diet, 150 minutes of exercise per week, maintaining an appropriate weight, no nicotine and low alcohol, and quality and sufficient sleep are all proven brain health strategies. Maintaining heart health is also key in reducing risk for dementia. This includes aiming for a blood pressure of 120/80 or less, normal cholesterol levels, and maintaining healthy glucose levels. Participating in social activities, learning new skills, and challenging tasks can also increase brain health.
Select nutraceuticals and botanicals have shown some modest but promising effects on cognitive decline and include bacopa, citicoline, lemon balm, curcumin, glutathione, ginseng, rhodiola, saffron, omega-3 fish oils, and melatonin.
In summary, brain fog in midlife women during perimenopause is very common and cognitive changes are typically mild and within the range of normal. Dementia in midlife women is rare, although awareness and prevention strategies do matter. Systemic hormone therapy is especially recommended for maintaining brain health in women who have their ovaries removed prior to age 52. It is not clear yet if naturally menopausal women with other minimal menopause symptoms will receive cognitive benefit or harm with MHT but, the research is compelling in two areas: 1. Start systemic MHT before age 60 or within the first 10 years of the final menstrual period 2. Avoid starting later than age 60 or after 10 years postmenopause. 3. If you have initiated in the safe and optimal window of time, the duration of use is individualized yearly. Changing key habits can optimize midlife health and decrease the risk for future dementia.
References:
[i] Maki P, Jaff N. Brain fog in menopause: a health-care professional’s guide for decision-making and counseling on cognition. Climacteric 2022;25:570-578.
[ii] Epperson C, Shanmugan S, Kim D, et al. New onset executive function difficulties at menopause: a possible role for lisdexamfetamine. Psychopharmacology 2015;232:3091-3100.
[iii] Maki P, Weber M. A research primer for studies of cognitive changes across the menopause transition. Climacteric 2021;24:382-388.
[iv] Maki P, Resnick S. Longitudinal effects of estrogen replacement therapy on PET cerebral flow and cognition. Neurobiol Aging 2000;21:373-383.
[v] Thurston R, Maki P, Chang Y, et al. Menopausal vasomotor symptoms and plasma Alzheimer disease biomarkers. Am J Obstet Gynecol 2023;S002-9378.
[vi] Weber M, Rubin L, Schroeder R, et al. Cognitive profiles in perimenopause: hormonal and menopausal symptom correlates. Climacteric 2021;24:401-407.
[vii] Gleason C, Dowling N, Wharton W, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomizerd, controlled KEEPS-cognitive and affective study. PLoS Med 2015; 12:e1001833.
[viii] Espeland M, Shumaker S, Leng I, et al. WHIMSY Study Groups. Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years. JAMA Intern Med 2013;173:1429-1436.
[ix] Henderson V, St John J, Hodis H, et al. Cognitive effects of estradiol after menopause: a randomized trial of the timing hypothesis. Neurology 2016;16:699-708
[x] Maki P, Gast M, Vieweg A, et al. Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial. Neurlogy 2007;69:1322-1330.
[xi] The 2022 Hormone Therapy Position Statement of the North American Menopause Society Advisory Panel. The 2022 Hormone Therapy Position Statement of the North American Menopause Society. Menopause 2022;29:767-794.
[xii] Rocca W, Bower J, Maraganore D, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007;69:1074-1083.
