Elizabeth Poynor, MD, PhD:
Our goal in this module is to educate OB/GYNs to be able to answer questions from their patients about brain health, cognitive issues, and dementia prevention. For the OB/GYN, the very first point is to realize that there is a concept called brain health and that there are ways to help prevent dementia through lifestyle.¹ Menopause and the perimenopausal transition is understood as a pivotal time period in women’s health, but it is also very helpful when women in their 30s or even 20s can set themselves up for a long-term journey in terms of brain health, because actions and behaviors at those ages do strongly influence outcomes later in life. 

Elizabeth Poynor, MD, PhD:
The OB/GYN is perfectly positioned regarding this aspect, because we are the healthcare professionals who often see women patients across their lifespan, from the teenage years when reproductive health first becomes a concern—perhaps the initiation of birth control—through late in life for menopausal concerns such as hormone replacement therapy. In contrast, internists typically specialize in the care of younger or older patients. Many women, once they find a gynecologist they are comfortable with, remain with that same gynecologist throughout life, including obstetric care for those who have children, so we can really develop lasting relationships. That continuity of care helps with detection of subtle issues that arise and evolve over time, such as gradual changes in memory or behavioral differences in the way a patient interacts with you. We additionally often benefit from easy rapport with our patients, such that our conversations within clinical visits naturally go beyond a simple review of systems to broader updates on the patient’s life, which may actually lead into medically relevant discussions.

Sharon Cohen, MD, FRCPC:
That is a very good point. As neurologists, we typically only see a patient regarding brain health once they have developed symptoms, by which time, a whole lifespan worth of bad habits may have accrued. We don’t usually have the opportunity to assess individuals prior to cognitive symptoms or as young adults.

Elizabeth Poynor, MD, PhD:
If I have a woman in my practice, potentially for a long time, I can begin to broach the topic of brain health when she reaches midlife. I would first introduce the brain simply as another system that we need to monitor as part of overall health, in the same way that comprehensive health care includes the cardiac system, metabolic and endocrine care, bone strength, etc.

For example, I would start out with: How are you feeling?  Could you be feeling better?  Have you noticed anything different since the last time I’ve seen you? I’ll then walk through each system within what becomes an overall medical history conversation. Using cardiac health as an example, I would ask: Are you exercising? Have you noticed any chest pain, shortness of breath, arm pain? I especially ask about cardiac symptoms that are more typical for women, such as nausea or abdominal pain. As I move through the systems, I would include brain health with questions such as: How is your memory lately? How is your ability to focus?

Elizabeth Poynor, MD, PhD:
When you start to ask about cognitive issues, it is quite important to lead into or frame these discussions with the fact that there are things we can do about cognitive decline.² Many women come into these conversations not wanting to know anything about it because they’re afraid of it. Women experiencing menopause-related brain fog are afraid to even bring it up to their doctors because they’re afraid of the possibility it may indicate developing dementia. Many of my patients have expressed gratitude, saying. “I'm so happy you asked about that because I just didn't want to bring it up.  I was afraid.“ In this respect, I try to alleviate fears by emphasizing that brain health is not passive, it is an active endeavor. We are not just trying to make diagnoses; we are being proactive in efforts toward prevention and early detection that allow the best possible treatments and outcomes. Patients really respond positively to this kind of shift in framework toward a preventive mode. Our medical community as well could benefit from greater understanding that there are actually things that you can do to benefit brain health. 

In gynecology we have a lot of experience with sensitive issues that we have had to step around lightly due to stigma or patient discomfort. We have experience asking the hard questions and bringing them up in a manner that doesn’t stigmatize the answers. For example, menopause can include issues like vaginal dryness and dyspareunia, but few patients will mention painful intercourse without being asked directly. Brain health is a similar issue, where unless we ask the questions, we're not going to get the answers. 

Sharon Cohen, MD, FRCPC:
I very much agree, and I approach discussions with my neurology patients similarly. It is important to start broadly by getting the patient’s overall impressions, so I ask general questions: “How's the brain doing? How do you find your thinking compared to a few years ago?  How are you functioning? How's your mood?” I do include mood as part of brain health. I find that these general questions open the door for discussion and that patients are often grateful to be asked. In my experience, patients generally either have not been asked about cognition or have had their concerns about memory brushed aside as normal aging rather than a legitimate issue that warrants further investigation. Some patients are reluctant or give minimal responses, but many take the opportunity to go into great detail. For example “I'm forgetting things more.  I'm having trouble coming up with names and words and it's frustrating me.” I let them know that memory loss is not normal, but that there are many possible causes and not to jump directly to Alzheimer’s as the only possibility. We will investigate, and we may find a straightforward answer, or it might be more complicated. However, if we don't look, then we won't know, and we might miss an opportunity to treat something that's treatable. This outlook empowers patients to feel that all is not doom and gloom and that catching a problem early allows something to be done about it.  

Elizabeth Poynor, MD, PhD:
Approximately 60% to 80% of perimenopausal women experience brain fog, but what is brain fog? How does it differ from mild cognitive impairment and how can we distinguish between them?³

For many women in the late reproductive years, what we call “brain fog,” meaning changes in memory or word-finding ability, actually is one of the first subtle indicators that estrogen levels are beginning to fluctuate.⁴ Discussion of brain health naturally dovetails into questions that I typically ask when assessing symptoms in my perimenopausal patients. This list includes items such as hot flashes, sleep disruption, metabolic changes, and changes in libido as indicators of menopausal stage. Change in memory or mood issues are on this list as they can be symptoms of perimenopause, but they may also be indicative of early cognitive impairment or risk for developing dementia.⁵

Perimenopausal brain fog typically manifests as word-finding difficulty and memory issues.⁶ The classic complaints are things like, “I can't remember that name”, or “I forget why I walked into a room”. But you can still learn, you can still function, you can still go about your daily life. Of importance, it really doesn’t progress or worsen. It makes patients uneasy, but it doesn’t impact their activities of daily living, and it doesn’t indicate emerging dementia. Opinions are mixed on hormone support for brain fog. Certainly some physicians do consider it and many patients do see cognitive improvement with hormone replacement therapy, but it is not a standard recommendation at this time.⁷

Beyond that characterization, we don’t really understand what it is because it hasn’t been studied rigorously. It has really only been acknowledged by the medical community recently and so we don’t have the data to make any more detailed statements about its mechanisms and etiologies. Brain fog is also seen with other hormonal shifts; for example, men treated with hormone therapy for prostate cancer often experience similar brain fog symptoms.⁸ There is a potentially interesting story about the neuroendocrinology underlying brain fog, but that body of research has yet to be fully developed.

Sharon Cohen, MD, FRCPC:
The term brain fog is used in other settings as well, beyond menopause. We see similar complaints from patients post COVID or other infections and in the context of chemotherapy. The differential diagnosis can be much broader depending on the situation of a particular patient.

Sharon Cohen, MD, FRCPC:
The Alzheimer’s Association has recently published clinical practice guidelines for primary care regarding Alzheimer’s disease and related dementias including an algorithm for evaluation of patients with suspected cognitive impairment, which would be largely applicable in the OB/GYN setting as well.⁹ 

Routine blood work would be within the purview of OB/GYN. If a patient complains of brain fog or memory problems, you would want to ensure thyroid stimulating hormone, vitamin B12, and glucose are normal. This is simple and not very time-consuming, but we are surprised by how many referrals we receive with no recent blood work. 

Elizabeth Poynor, MD, PhD:
OB/GYNs should be performing a routine set of labs for patients we see on an annual basis. These include levels such as cholesterol, B12, and measures of insulin resistance such as hemoglobin A1C, which can reveal conditions that we can manage without needing specialty referrals. It is worth reiterating that we ourselves can perform many of the components of differential workup for cognitive symptoms and in many cases make effective interventions before consulting neurology.  

Elizabeth Poynor, MD, PhD:
It is important that you bring up mood as part of brain health, because depression is extremely common in women and can greatly impact cognitive function.¹⁰ I also mention the contribution of sleep to brain health when talking to patients, as we see so much sleep disruption in midlife women as well.¹¹

Sharon Cohen, MD, FRCPC:
This can be a chicken and egg problem: are patients anxious, depressed, not sleeping well because they’re worried about memory loss? Or is it the other way around, with hormonal changes or some other common factor causing the depression and anxiety which cause you to be distracted and forgetful? 

I do tell patients that they have come to the right place and that we will work through these issues carefully because they are complicated.  It can be hard to determine whether a symptom is significant or just a bit of forgetfulness, but unless we investigate, we will have no chance of finding any meaningful answers.  

Sharon Cohen, MD, FRCPC:
Dietary recommendations can be complicated, especially for patients who are managing multiple health conditions. What can we tell a patient with diabetes, lactose intolerance, or celiac disease that will additionally be best for their brain health? You and I don’t have the knowledge of a nutritionist or have all the information at our fingertips, and patients can be quite sophisticated in the questions that they bring to us. We do know some basics, however: More fruits and vegetables, not too much red meat or animal fat. The MIND diet was designed based on the Mediterranean diet with specific modifications to include factors with evidence for dementia prevention.¹² 

Elizabeth Poynor, MD, PhD:
An OB/GYN can be confident addressing some confounding conditions that may impact cognitive issues, such as sleep and mood. Sharon, is there any cognitive testing such as the Mini Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) that could be administered in the OB/GYN setting?  What would be the potential utility of these assessments for us, without having expertise in dementia?  Should we be taking these steps before specialty referral to reduce the burden on your clinics?

Sharon Cohen, MD, FRCPC:
The MMSE and MoCA are cognitive screening tests that take approximately 10 minutes.¹³ MoCA is more appropriate for patients who are still high functioning, as likely to be seen in an OB/GYN setting, whereas MMSE is more likely to be used when someone is more impaired. Both are brief tests that need to be administered and scored appropriately and provide valuable information as to whether or not a patient falls within the normal cognitive range or various ranges of impairment. At the memory clinic, we perform much more in-depth assessment, but we're still very appreciative when a patient already has some baseline testing upon referral.

A screening test alone can't make a diagnosis, but that cognitive score in combination with questions about daily function can tell you whether a patient is within the realm of mild cognitive impairment (MCI) or dementia. An OB/GYN can take a basic functional history with questions such as: Have you had any changes in your level of independence? Are there any activities you've had to give up or are there tasks other people have had to take over from you? Patients who have evidence of cognitive impairment on an MMSE or MoCA but can still perform daily activities on their own, even if they are more frustrated or need more reminders, are in the MCI category, whereas cognitive symptoms that interfere with day-to-day function begin to cross the line into dementia.¹⁴

Elizabeth Poynor, MD, PhD
Resources are a key component of the strategy to approach brain health and cognitive issues. Proactive identification of appropriate resources for referral allows clinicians to have a plan before the patient presents in the clinic. We don’t want to find ourselves in a situation where a patient shows what may be signs of MCI or early dementia that warrant investigation, but we don’t know where to send her. It is vital for each OB/GYN to establish those referral patterns, to identify the resources within their community, and to be in communication with specialists available for consults. Implementing regular cognitive screening in our patients is important, but it is equally important that we have next steps in place to follow that screening.

Sharon Cohen, MD, FRCPC:
A crucial area of knowledge for OB/GYNs is when should a patient be referred for more formal cognitive assessment?  When a patient demonstrates mild symptoms, how can you determine whether these are due to lack of sleep, for example, or when they call for more intensive workup? We don't want to falsely reassure people, but we also don't want to overdiagnose or raise unnecessary concern. It is important to draw that line with some confidence, which requires education on the part of clinicians to look for red flags and risk factors. 

Elizabeth Poynor, MD, PhD:
We don’t want to send every perimenopausal woman for neurologic testing, because that’s not necessary and would be a little disarming for the patient. However, if cognitive symptoms go beyond what is typical brain fog or worsen or expand in scope over time, referral to a neurologist is appropriate. In addition, if a patient has a family history of dementia or is known to be APOE4 positive, I have a much lower threshold to make that neurologist referral.

Sharon Cohen, MD, FRCPC:
When a patient is first referred to me for neurologic evaluation, I begin by taking a dementia-focused history.¹⁵ As Elizabeth mentioned, classic perimenopausal brain fog includes cognitive symptoms such as word-finding difficulty, slightly impaired short-term memory, and maybe some executive dysfunction. Those are exactly the early symptoms of Alzheimer's disease as well, so I would delve into other aspects of the patient’s medical history that are potentially relevant to AD. Do they have vascular risk factors or other risk factors for neurodegenerative dementia? Do they have a history of dementia in their family?  Are they APOE4 carriers? Having 1 copy of ApoE4 confers a 3-fold higher risk of AD over the general population. Having 2 copies of ApoE4 confers a 10- to 12-fold increased risk of AD. 

Following history taking, it is important to perform cognitive testing. History is sometimes misleading as patients differ in their ability to detect and/or describe their own symptoms and we cannot make a clinical diagnosis based on symptoms alone. Some patients are very sensitive to slight changes and can eloquently describe their memory concerns and their impressions of a decline in abilities, while others complain very little and have only come to the clinic at the request of a family member who has noticed forgetfulness. Cognitive testing will clarify whether there is objective evidence of cognitive impairment.

Third, I evaluate level of function: To what extent have cognitive or behavioral symptoms interfered with the patient’s activities of daily living? Are they still independent and able to perform their usual activities at their usual level? Are they working, banking, shopping, driving? It is important to recognize that we all have different strengths and skill sets. For example, the daily functional expectations for a mathematician may be different from those of a poet, and if the mathematician can no longer manage their banking that might have different implications than for the poet for whom one might expect literacy skills to be strong at baseline. 

Next, a general neurologic examination would be performed to investigate potential neurologic causes of the cognitive symptoms. Are there signs of silent infarcts, such as dragging one foot or facial asymmetry? Are there signs of normal pressure hydrocephalus such as magnetic gait, or more commonly, some parkinsonian or extrapyramidal signs, such as shuffling, rigidity, or bradykinesia? Finally, blood work and a structural brain scan would be ordered. These would expose conditions such as hypothyroidism or B12 deficiency masquerading as cognitive decline as well as discovering any structural brain abnormalities such as strokes or tumors on a scan.

Sharon Cohen, MD, FRCPC:
Once we have the information from that basic initial workup, we treat factors that may be contributing to the cognitive impairment. For example, if there is depression or a sleep disorder, we treat those conditions and see whether the cognitive symptoms resolve. If cognitive symptoms do not improve, that's when we would go on to include Alzheimer's biomarkers in our investigations, particularly if there are risk factors for AD. 

Finally, we should admit to ourselves as healthcare professionals that we cannot always tell conclusively what is causing a symptom or collection of symptoms and that we can be fooled. We sometimes treat according to a presumptive diagnosis on clinical grounds and see if that resolves the symptoms, but when it doesn't, we need to dig deeper with biomarker testing or other investigations.

Sharon Cohen, MD, FRCPC:
Patients should be counseled that MCI is not a specific disease. MCI is a syndrome in which cognitive test results are lower than normal based on an individual’s age or education, but the individual is still functioning independently. MCI can be due to many different causes, with AD being only one possibility. The treatment for MCI will ultimately be guided by its cause and therefore it is important to investigate etiology thoroughly.

It is also very possible to have several contributing factors, such as, for example, a main underlying cause of depression which is further exacerbated by lack of sleep and by perimenopausal hormonal fluctuations. Each individual situation can be complicated, but we still should make the effort to figure it out. We should not just write off these symptoms because they are mild and tell our patient not to worry just because they are still independent. Loss of independence is highly feared; progressive conditions need to be diagnosed and addressed early for optimal outcomes.

Elizabeth Poynor, MD, PhD:
For the OB/GYN, the key question is the distinction between brain fog and MCI preceding dementia. Almost every woman experiences some degree of cognitive issue at perimenopause or menopause, so it is important to drill down on those distinctions to identify women with real cause for concern. Otherwise, OB/GYNs may spend a lot of time with unnecessary neurologic consultations over normal hormonal effects.

Sharon Cohen, MD, FRCPC:
In my practice, counseling on brain-healthy lifestyle strategies can be a very quick or a very lengthy conversation. The details depend on the patient. For those who are physically active, engaged in their jobs and family life, sleeping well, and generally engaged in activities that maintain brain health, I say “Great! Keep doing those things!” For others, there may be a million questions requiring an hour or more of counseling. Time-based billing codes are very helpful if your billing system allows, because there is no one-size-fits-all discussion. Specific issues that are raised, such as addressing vascular risk factors or sleep problems or stress management, can be billed under those codes. These conditions are health problems to be addressed for their own sake but also as contributors to poor brain health. Regardless of how we bill, we need to make time to discuss lifestyle strategies to mitigate dementia risk, because if you embark on the topic of brain health with your patients but don’t offer any tangible actions, you're really not doing your patients a service. 

Elizabeth Poynor, MD, PhD:
Our billing and reimbursement process doesn’t realistically capture the way we as healthcare professionals counsel patients on lifestyle recommendations. Really, cardiac health is brain health is metabolic health is bone health; it’s all linked. It amazes me sometimes how straightforward the counseling can be, because the same interventions and lifestyle modifications benefit so many systems and so many conditions, including as we are now discussing, brain health and dementia prevention. We would benefit from reimbursement pathways that reflect this. 

Sharon Cohen, MD, FRCPC:
Cognitive impairment is so prevalent, and dementias including Alzheimer's are on the rise. Millions of people are affected, and we don't diagnose early enough or accurately enough. Having more healthcare professionals interested in and able to take the initial steps of identifying symptoms of potential dementia is a blessing. As a behavioral neurologist, I am thrilled that some OB/GYNs want to share in this endeavor of promoting brain health in their patients.

Elizabeth Poynor, MD, PhD:
This is a great collaborative model of OB/GYNs with neurologists, because there is meaningful crossover with the impact of sex hormones on brain health outcomes. OB/GYNs have potential to raise awareness and reach many women with an understanding of the components of good brain health and the contributing factors toward risk of cognitive decline and dementia.