Brain and cognitive health at midlife

Midlife—from approximately ages 30 to 60 years—is a time of social and biological change for women. Many will experience fertility or pregnancy concerns, raise children, pursue career advancement, and become caregivers for an aging parent. All will eventually experience a loss of ovarian function. Researchers and clinicians have greatly improved public awareness of the ways social roles and hormones affect medical conditions, mood, and sleep. However, the far-reaching influence of midlife social and hormone change on cognition is less well-understood. It is critical that healthcare professionals who treat midlife women understand common cognitive health concerns, ways to address these concerns, and the link between midlife and later-life cognitive health.1 WHAT IS BRAIN AND COGNITIVE HEALTH? Brain health refers to the health of all functions controlled by the brain, including social, physical, mental, and cognitive health. Cognitive health means the health of thinking skills, such as memory, attention, speed, visual-spatial perception and navigation, and executive functions such as multitasking, reasoning, and planning. Healthy cognitive aging typically entails minor compromises in thinking skills over time but does not include decline to the level of impairment. WHAT BRAIN AND COGNITIVE SYMPTOMS ARE COMMON IN MIDLIFE WOMEN? At midlife, 40% to 60% of women experience cognitive symptoms.2 Often referred to as “brain fog,” these symptoms can include feeling mentally foggy or sluggish, reduced ability to concentrate or focus for longer periods, trouble staying on track with tasks or conversations, difficulty recalling names or words, and forgetting to-do list items. Such symptoms can cause distress, especially for women who have witnessed a family member or friend decline with dementia. However, dementia-related cognitive symptoms are relatively rare at midlife, and when they happen, are more frequent (eg, occurring several times per week, day, or even hour), and more severe (eg, forgetting a close friend’s name or a critical task). WHY ARE COGNITIVE SYMPTOMS COMMON IN MIDLIFE WOMEN? At midlife, a wide variety of factors known to affect cognitive health become more likely. Gender-influenced social role expectations related to work, childcare, and eldercare can create sleep disruption and stress and can even lead to delaying one’s own medical care or experiencing symptoms of depression. Although poor sleep and stress are often normalized in midlife, they have potential to worsen brain and cognitive health. For example, a single night of poor sleep has been shown to change the neural signature of memory encoding,3 which in turn may reduce ability to remember daily tasks. Chronic stress, such as strain linked to caregiving, creates a neurochemical cascade that can disrupt and even damage memory systems.4 Adding to the problem, alcohol and many over-the-counter and prescription medications, when used by women to address sleep and stress concerns, can reduce memory function via anticholinergic effects if used over long periods of time.5 DOES MENOPAUSE CHANGE MIDLIFE COGNITIVE HEALTH? Hormone changes during menopause can negatively affect thinking at a level that is measurable on standardized cognitive tests. In particular, women show reduced scores on tests of verbal learning and memory changes across the menopause transition.6 However, these cognitive changes are time-limited and for most women do not rise to the level of impairment.6 Whereas mechanisms of hormone influence on midlife cognitive health are incompletely understood, one contributor is that brain-memory systems are rich in estrogen receptors, and throughout life, estrogen supports the health and function of memory.7 Loss of estrogen means loss of that support and the need for neural recalibration. Hormone changes also indirectly drive memory concerns through their effect on sleep, mood, and stress. For most women, reassurance that minor cognitive concerns are common and time-limited is appropriate. Referrals for clinical assessment of memory should be reserved for women reporting severe or frequent symptoms. CAN REPLACING HORMONES ALLEVIATE MENOPAUSE-RELATED COGNITIVE CHANGES? For women with early or premature menopause (age <45 y), hormone therapy (HT) may be important for avoiding cognitive concerns in midlife and beyond.8 However, for women experiencing typical menopause, research does not currently support use of HT for cognitive preservation or dementia prevention.9 At the same time, HT for women with typical-age menopause may be an effective solution for symptoms that can indirectly affect cognition. For example, HT can reduce hot flashes, which can improve sleep, which in turn may lessen brain fog. BEYOND HORMONE THERAPY, HOW CAN WOMEN ADDRESS MIDLIFE COGNITIVE SYMPTOMS? The best way to address midlife cognitive symptoms is to target the root cause of the symptoms. For example, the most effective interventions may be HT, referral for a sleep study or other medical assessment, recommending changes in medication use, providing stress management, sleep hygiene, care-partner resources, or referral to counseling or psychotherapy. Healthcare professionals have a critical role to play in educating and encouraging women to address these risks for poor cognitive health, particularly because they can affect not only midlife cognition but also cognitive outcomes in aging. Up to 45% of current cases of dementia can be attributed to lifestyle and environmental risks, including diabetes, hypertension, physical inactivity, depression, and hearing loss.1 Most of the lifestyle-based risks have key effects when present at midlife. Accordingly, intervening at midlife with enhanced lifestyle measures—exercise, healthy diet, smoking cessation, moderation in alcohol, or hearing aids—may improve not only current health and quality of life, but also long-term cognition, heart health, and cancer risks. IS THERE A DIRECT WAY TO IMPROVE COGNITIVE HEALTH? Although cognitive change at menopause typically does not rise to the level of impairment, women may benefit from use of cognitive supports (eg, notes, lists, and reminders). These can reduce chances of memory or attentional errors, even in chaotic environments. In addition, challenging cognitive activity (eg, learning a language or instrument or working in an intellectually challenging occupation) can support brain health in aging by building cognitive reserve. Finally, although cognitive impairments are relatively rare at midlife, women with serious concerns should be referred for a neuropsychologic assessment to further understand the nature of their cognitive issues. KEY SUMMARY POINTS Cognitive symptoms, often referred to as “brain fog,” are common at midlife and can relate to the menopause transition as well as to psychosocial change, medical conditions, and medications. Cognitive change across the menopause transition is measurable but typically remains within the normal range and does not represent clinical levels of impairment or permanent change. Hormone replacement therapy may be important for maintaining cognitive health in women with early and premature menopause; however, hormone therapy for the primary purpose of cognitive health is not supported for women experiencing typical menopause. Outside of hormone therapy, medical management of cardiovascular risks and lifestyle change can powerfully address cognitive concerns in midlife and in aging. CLINICAL RECOMMENDATIONS Discuss cognitive health with women in perimenopause. Normalize cognitive symptoms as common and time-limited in perimenopause; at the same time, refer women for cognitive testing when symptoms are frequent or severe. Review possible role of hormone replacement therapy for cognitive health with women experiencing early or premature menopause. Encourage addressing the root cause of cognitive concerns, for example through healthy lifestyle behaviors, medical condition evaluation and monitoring, and stress management. Coming next in theStep-by-Stepseries: Nick Panay, BSc, MBBS, FRCOG, MFSRH, consultant gynecologist and Professor of Practice, Imperial College London, will canvas the etiologies, diagnostic approaches, and unique management strategies for patients experiencing premature loss of ovarian function before the age of 40.This article is part of the ongoing series Menopause Step-by-Step, a monthly Menopause education feature.10 The Editors of this series are Dr. Cynthia Stuenkel, Dr. Cheryl Cox Kinney, and Dr. Isaac Schiff.