Building Brain Health Bridges: Clinical Strategies for Early Intervention and Broad Impact

Introduction

Lisa Phipps (PharmD): Welcome back. Our next session is Building Brain Health Bridges: Clinical Strategies for Early Intervention and Broad Impact, presented by Dr Marwan Sabbagh, who is the Moreno Family Chair for Alzheimer's Research and Vice Chairman for Research and Professor and Director of the Applied Alzheimer's Research Laboratory in the Department of Neurology at Barrow Neurological Institute in Phoenix, Arizona; and Dr Rajeet Shrestha is a Senior Attending and Physician in Psychiatry and Assistant Professor of Psychiatry at Case Western Reserve University and University Hospitals at the Cleveland Medical Center in Cleveland, Ohio.

[00:00:40]

Faculty and Disclosures

You can see their disclosures here.

[00:00:45]

Learning Objectives

And the learning objectives today are to:

Analyze the benefits of optimizing brain health to prevent cognitive decline before it occurs;

Apply best practices for discussing brain health and cognitive decline with patients for - during routine care; and

Assess modifiable risk factors for cognitive decline and dementia at patient visits.

[00:01:04]

Let’s Vote!

So let's vote.

[00:01:08]

Poll 1

How many people aged 50 to 65 years do you provide care for in a typical week?

One to nine;

10 to 25;

26 to 50;

51 to 100;

Over 100 patients; or

Is this not applicable to you.

[00:01:43]

Pretest 1

Okay. let's do our first pretest question. A 53-year-old Black man is referred by his primary healthcare professional to your neurology clinic for evaluation of hand tremor. Your initial patient history and review of systems includes several ongoing health issues that the patient considers to be currently well managed. In your discussion with the patient and note back to the primary healthcare provider, would you recommend to be monitored closely and reevaluated to most likely mitigate his risk of developing cognitive impairment or dementia in the future?

Drinking 4 cups of coffee per day;

A history of depression currently treated with an SSRI, PHQ-9 score equal to 4 with a range of zero to 27;

Blood pressure in the office of 152 over 85, currently on an ACE inhibitor, and he takes this regularly; or

He's overweight, BMI 28, exercises regularly 30 minutes’ walk 4 to 5 times weekly.

So this patient is a 53-year-old Black man referred by his primary healthcare provider to your neurology clinic. These are the other things that he has going on with him. And which of these would you recommend to be monitored most closely and reevaluated to mitigate his risk of developing cognitive impairment in the future?

See what everybody thinks. And we have quite a spread here. So it looks like 39% and 40% are our 2 biggest ones. And most people chose either the blood pressure or the history of depression. So we'll see how things go in our posttest.

[00:03:54]

Pretest 2

So our next pre-test is you have treated a 65-year-old woman for neck pain following a car accident. On follow up visit, her neck symptoms are much improved, but she mentions she has had problems sleeping and on a few occasions has gotten lost while driving and has forgotten people's names. She's concerned that these may be symptoms - early symptoms of Alzheimer's disease. What is the next best step to address her concerns during this visit? Do you:

Reassure her that occasional memory lapses are normal within aging, but order Alzheimer's blood biomarker testing to address her concern;

Do you perform comprehensive cognitive behavioral assessment before pursuing potential diagnostic testing;

Do you order a cognitive laboratory panel to rule out common medical issues that can affect cognition, neuroimaging to rule out issues such as tumors or infarcts, and APOE4 genetic testing to assess for Alzheimer's disease related e4 status; or

Order a sleep study, but hold off on prescribing a hypnotic.

What do you think? Next best steps to address her concerns. And survey says, C, 56% of people perform a cognitive behavioral assessment before pursuing potential diagnostic testing, and 32% order cognitive laboratory panel to rule out common medical issues and neuroimaging to rule out issues such as tumors or infarcts and APOE genetic testing.

So let's go through our presentation and see what we come up with post-test. Dr Sabbagh, I will turn it over to you here.

[00:06:10]

Evidence-Based Strategies for Brain Health Preservation

Dr Marwan Noel Sabbagh (Barrow Neurological Institute): Thank you, Lisa, and welcome, everyone. My part of this conversation is to discuss evidence-based strategies for brain health prevention. I am a cognitive behavioral neurologist, and I have these conversations a lot in my clinic, and I suspect you do, too. So being informed here is going to be important.

[00:06:31]

Poll 2

So the first thing we're going to do is another poll question, which is, of your patients, 50 to 65 years of age, how many proactively ask you for information regarding possible future cognitive decline or dementia?

None;

Few;

Half;

Most;

Almost all.

While you're thinking about answering that question, I will say to you, from my perspective, particularly the adult children of patients who have had dementia, I get that question a lot. So it depends if they are—if it, you know, their adult caregivers of their elderly parents, that would be almost 100%. So it just really depends on who you're talking to.

[00:07:14]

Typical Course of Dementia

So I wanted to tell you that we get the question a lot, what's the difference between Alzheimer's and dementia? I'm going to answer specifics around this in the next slide, but I just want to bring this up to you all because these are categorical definitions. Mild cognitive impairment and dementia are categorical definitions. Much like cancer is a categorical definition.

Dementia means that you have cognitive impairment that is severe enough to cause loss of function or loss of independence, and mild cognitive impairment is loss of cognition but still retained independence or functional independence. So dementia is just a more severe state. Mild cognitive impairment could be cognitive memory loss but still independent. So the reason we understand this is that in the journey you start with normal cognition, you progress to mild cognitive impairment and then you progress to dementia.

When I see a patient—when I talk about categorical definitions, I will say mild cognitive impairment due to dot, dot, dot, Alzheimer's, Parkinson's, Lewy body or dementia due to Alzheimer's, Parkinson's, Lewy body, etc.

[00:08:26]

Not All Dementia Is AD

Because there are categorical definitions and meaning that dementia is the category, Alzheimer's is the type, Lewy body, Parkinson's, stroke, normal pressure hydrocephalus, hypothyroidism, infections, etc, frontotemporal dementia. There are many, many causes of dementia or mild cognitive impairment. Alzheimer's is the most common. Roughly two thirds to three quarters of all dementia, neurodegenerative progressive cognitive disorder with functional loss is related to Alzheimer's disease. Many of them have mixed pathology. But the point is, is that you should say dementia or mild cognitive impairment due to and then put in the etiology. So categorical etiological.

[00:09:10]

Major Changes in the Brain due to AD

So when we go specifically to Alzheimer's disease you're talking about 3 major neuropathological features. One is the accumulation of amyloid in the form of the N-terminal stage which is the plaque. Second is the neurofibrillary tangle. And third is the neurodegenerative which is manifested by atrophy.

So we know—and this is important for all of you to consider—that amyloid is the early seminal event that leads to the triggering of the inflammatory response. The neurofibrillary tangles spread, and the advanced stage is the neurodegeneration. So we start with amyloid, we end with neurodegeneration. But the correlation of clinical progression is more related to the spread of tau and tangles than it is the amyloid.

[00:10:12]

AD Pathophysiology Begins Decades Before Symptoms Appear

So the reason I say this to you is that we know by the time they walk into your clinic and mine, they've been accumulating pathology for up to 20 years. So remember that the dementia and the mild cognitive impairment are the advanced terminal phase of the disease. You start with the accumulation of amyloid, and then you trigger the tau, and then you trigger the neurodegenerative changes, and then you trigger the cognitive symptoms and then the internal stage is the dementia.

So as you see in this slide here, the accumulation of pathology occurs before onset of symptoms. And then you get symptoms and then you get advanced symptoms. So I want you to understand that the—I like to talk about this to my patients like—like diabetes.

So in diabetes, right, your blood sugars start to go up. And the end terminal stage is the blindness, the neuropathy and the renal failure. We're wanting to detect people prior to the end terminal stage. And so that's what I'm saying to you is that the pathology changes and then the clinical symptoms start.

[00:11:25]

Early- vs Late-Onset AD

We talk about presenile and senile onset or early onset or late onset. Presenile means young onset meaning below age 65. You have to look for the autosomal dominant mutations. What I see a lot of in the young onset Alzheimer dementia is down syndrome, so trisomy 21. Now the life expectancy of a down syndrome is about the mid early to mid-60s. They are accumulating amyloid pathology by age 12. You can detect it by amyloid PET by age 37. They start getting clinical symptoms by age 44.

Down syndrome, far more prevalent than presenile 1 or presenile 2. So I just want you to be aware that, now down syndrome people are walking into my clinic in their early to mid-40s with cognitive decline, which is Alzheimer's disease, and their lifetime probability is somewhere in the 90% to 95% of developing Alzheimer dementia if they live long enough.

Late onset is but it will be called senile dementia due to Alzheimer's disease is going to be over age 65, maybe APOE related. And of course, if you're a homozygote—APOE4 homozygote, you tend to get your symptoms 68 to 72. The heterozygote, 74 to 78 and noncarrier in the 80s. So I just want to say to you that these are the presenile and senile onsets.

[00:13:00]

The Coming Dementia Pandemic

So the pandemic of Alzheimer's or dementia is growing. We expect that it's going to keep getting bigger and will double. So right now we estimated it's roughly about 7 million people. We expect that to double by 2060. And so we're seeing more and more people developing Alzheimer dementia. And the problem is—and that's why I think it's imperative that all of you become experts here is that we don't have a lot of dementia specialists. We need to see them growing in geriatrics, neurology and psychiatry.

I happen to say I jokingly know most of the people in my field. They're just not that many of us. Infrastructure is not prepared for this, and the solution is not institutional based care. We need to find ways to intervene and intercede prior, or earliest or prevention to bend this curve.

[00:13:58]

What Does the AD Population Look Like?

So the other thing you need to understand, though, is that there is a gender prevalence more women than men. Roughly speaking, 60/40 or 66, two thirds, one third. It is not simply a differential survival effect. It is a plain fact of medicine that women outlive men. The life expectancy of a man is about 76, 77. The life expectancy of a woman is about 82. Even when you factor in the differential survival effect, women get more Alzheimer's than men. We can spend all the rest of the day debating why and how.

But the age also drives whether it's more in the MCI or more in the dementia. And clearly the younger you are, the more likely it's to be MCI. And the older you are, the more likely you have progressed through dementia. And so this is the breakdown of what an AD population looks like.

[00:14:48]

Why Amyloid Matters in AD Treatment

So the skeptics who say amyloid hypothesis is irrelevant, I would like to reorient you to the possibility that amyloid is the earliest seminal event. And now all species of amyloid are not toxic. When you cleave amyloid with APP, you get a nascent protein called a monomer. But only when you get to the oligomeric phase protofibril, fibril and plaque, does it become toxic.

So this is super important because amyloid - only oligomeric species and protofibril species and plaque cause the damage to the environment, and you have to see a lot of accumulation before you get the tau spread. So the spread of tau predicts clinical progression, not the spread of amyloid.

We do know that there is an Icelandic mutation which can reduce risk. But we also know that the questions that we are facing is not treating with anti-amyloid drugs. The question we're facing in the field is, are we treating too late? Is it really best to target amyloid in the early symptomatic phase, or should we be targeting patients in the presymptomatic phase? So let me kind of walk you through that.

[00:15:58]

2 FDA-Approved Antiamyloid mAbs for AD

There are 2 FDA-approved monoclonal antibodies that target amyloid, lecanemab and donanemab. Lecanemab is an intravenous every 2 weeks for 18 months, and removes about 71% of the amyloid. And 50% of patients are amyloid negative at 12 months, and 75% are amyloid negative at 18 months. And as long as you manage or, you know, mitigate the ARIA concerns, patients can do very well.

Now they have a maintenance therapy and a subcutaneous therapy. These are only patients in mild cognitive impairment or mild dementia due to Alzheimer's disease. And you have to confirm that they have amyloid. You should check their APOE genotype. You should also quantify how many microhemorrhages they have on MRI.

Donanemab, similar, intravenous, once a month with a dose titration schedule of 350 to 700 to 1050 to a 1400 mg a fixed dose schedule, not a weighted dose schedule. And you basically treat till they are amyloid negative and then you stop the treatments.

So these are the 2 monoclonal antibodies. And the skeptics in this audience need to understand these drugs remove amyloid do them very, very well. But you only see about a 28% to 30% slowing in the rate of decline because you're only targeting amyloid, not tau, not neuroinflammation. So it's not a 1-to-1.

Again, people in my field are starting to say, is it that we're treating too late, not whether it's a good target or not?

[00:17:31]

Current Clinical Trials in AD Prevention

And the reason I say this to you is that there is now a lot of focus on shifting these treatment modalities to presymptomatic phases, meaning biomarker positive, you’re accumulating pathology. You're not having clinical symptoms. And so now there are multiple clinical trials that are targeted on secondary prevention.

So secondary prevention is the meaning that they're biomarker-positive, clinically asymptomatic, unimpaired. And so they would be treated with lecanemab, that's the A3-45 study; the donanemab, that's the TRAILBLAZER-ALZ3. And there's a new drug you need to be aware of coming potentially is remternetug, which is the son of or brother of donanemab and would be pretty fantastic, because it removes amyloid very, very aggressively and very, very robustly.

So the point here is that we're moving even earlier than clinical symptomatology, clinical symptoms of mild cognitive impairment or mild dementia to go to the earlier stages, the presymptomatic stage. And so there's a shift toward secondary prevention.

While we're doing all this in the therapeutic, pharmacological or pharmaceutical area, the question is, what about lifestyle-directed strategies?

[00:18:50]

Dementia Prevention Across the Lifespan

So I love this slide. People quote this up, down, left and right about the idea that lifestyle-directed strategies can reduce overall risk. And if you look at the Lancet Commission updated deck here on the right-hand panel, you see that there are some evidence that you can reduce risk by 45% due to modifiable risk factors. And I love that and I really endorse that. I recommend this to my patients. I discuss this with my patients.

But you need to understand that these renderings are based on population health strategies. So if I am a low educated person, if I'm going to get more—if I go take a college course, is that going to mitigate my risk? My point is that these are population-based outcome measures. But we have to try to incorporate seeing if - treating these individual risk factors can mitigate their overall risk.

So we know that if you do all these things, your risk reduction is quite significantly reduced. But it's not—I just want to be very clear that, this is based on popHealth, not on individual recommendations.

[00:20:10]

WHO 2022 Recommendations Risk Reduction of Cognitive Decline and Dementia

So you know, multiple commissions. I already told you about the Lancet Commission. I need you to know about the World Health Organization. There's actually National Academy of Sciences, Medicine and Engineering has a recommendation. And the World Health Organization's recommendations is specifically about aggressive medical management, diabetes, hypertension, hyperlipidemia, because they're normalizing your health parameters, actually has neuroprotective effects.

Then you add nutritional aspects, then you add cog stim. Then you add other things as well. So if you see this the recommendations are aggressive weight management, aggressive normalization, aggressive physical activity, tobacco cessation, cog stim. And this is the World Health Organization's recommendations.

[00:21:03]

American Heart Association 2021 Primary Care Agenda for Brain Health

Another group is American Heart Association. And they recognized very early that brain health and heart health are interchangeable or interrelated to one another. You start brain health by having good heart health. And so they focused really on what you can do in the simple 7, BMI, stop smoking, physical activity, eat a healthy diet, optimize your cholesterol, optimize your blood pressure, optimize your fasting glucose.

And then they added other things like social isolation, hearing loss, education, sleep impairment and depression. So these are the American Heart Association's recommendation for brain health.

[00:21:49]

Impact of Vascular Health on Dementia Prevention

And people have tried to operationalize the vascular health for dementia prevention. So the SPRINT-MIND trial was specifically saying if we aggressively manage their blood pressure, would it reduce overall risk of developing dementia? And the answer is very much so. And if you look at it in aggressive management of blood pressure below—optimizing your blood pressure to below 120 mm Hg, you see that your risk reduction is somewhere between 15% and 19% risk reduction. So 1 of the most sustainable and reproducible and clear recommendations is aggressive blood pressure management.

People never think about blood pressure recommendations as it comes to brain health and cognitive protection. But of all the recommendations, the thing that has been consistently shown is aggressive blood pressure management.

There is now prevention trials around the use of reducing cholesterol. And that study is underway.

[00:23:03]

Diet Can Influence Cognitive Decline and AD Pathology

Now, what about diet? And the answer is there is the MIND-DASH diet. This is from Martha Clare Morris. Martha Clare Morris is at Rush University, and she's basically saying that if you adhere strongly to a brain healthy diet of leafy vegetables, nuts, berries, beans, whole grains, seafood, poultry, olive oil and wine, and avoid red meat, butter, cheese, pastries and fried foods, your risk goes down, but more importantly, your risk of developing Alzheimer's is lower over time in people who, that's the green line, highly adherent to this diet vs poor adherence to the diet.

And the amount of pathology you have in the brain is lower as well. So this is clearly evidence that these pathologies work.

[00:23:56]

FINGER Study: Multidomain Lifestyle Modification

Two studies you need to be fully aware of that have read out 10 years ago, the FINGER study showed—this is from Scandinavia. This is Miia Kivipelto’s work, that if you randomize people to a aggressive medical management plus cog stim plus physical exercise vs just recommendations, you showed that you not only reduced risk of overall, but you actually stabilize their cognitive abilities. And if you didn't do these things, you actually did not have procognitive effects.

This lit up 10 years ago when I remember being in these meetings, people were super excited about this. So excited that there became worldwide FINGER studies and multiple countries, multiple groups around the world started to reproduce these kinds of studies.

And just this year, in 2025, the US POINTER study, which is the next slide, reported out their data. And this is the US version of the FINGER study just reported about 3 months ago at the AAIC.

[0:25:05]

US POINTER: Multidomain Lifestyle Modification

And what it showed here, again, is that people were randomized to aggressive medical management plus cog stim plus physical exercise or none of the above. Or they basically—just the untreated group, this was self-guided. So instead of being coached and managed and supervised, you were just basically handed us some pamphlets saying, do this yourself.

And what it showed is that if you did it, your overall risk reduction went down. This was a huge study. 2,111 people aged 60 to 79. And showed that again, physical exercise, diet, cog stim health coaching, that it did reduce overall risk over time and that it showed that a significant benefit in a structured high intensity intervention. And there was greater benefit for those with lower cognitive function at baseline.

So the point is, is that lifestyle-directed strategies work. They work. Now we don't know how much they reduce overall pathology, but we do know that they help their procognitive and help overall health and cognitive outcomes. So you can do them. And we can talk about focusing on the therapeutics as well. So it's not either or, but it's both.

[00:26:23]

Key Takeaways

So the key takeaways are is that the reason you want to make these recommendations in your practice is that the pathology is accumulating prior to onset of clinical symptomatology. And so the end terminal stage is the mild cognitive impairment and dementia. Clinical markers and biomarkers tend to track AD progression are available. The fundamental hypothesis is that earlier treatment may slow disease progression.

About half of dementia risk can be mitigated by modifiable lifestyle and health related strategies. Large randomized studies have shown meaningful impact of structured multidomain interventions, and patient education and communication are key to improved dementia prevention as part of routine care.

And with that, I will hand it off to my colleague, Dr Shrestha.

[00:27:17]

Discussing Brain Health With Patients in Clinical Practice

Dr Rajeet Shrestha (University Hospitals Cleveland Medical Center): Hey, thank you, Dr Sabbagh. So I am Rajeet Shrestha. I'm a Neuropsychiatrist and a Cognitive Specialist. And I also see a lot of patients in our memory clinic at different stages of cognitive concerns. And all the good information that we just reviewed, that we have gained from research, I'm going to talk about the best practices to discuss those and utilize those to benefit our patients in our clinic.

[00:27:45]

Poll 3

First, we'll start with a poll. With your patients 50 to 65 years of age, how often do you discuss cognitive and memory concerns or dementia prevention planning?

Never;

Rarely;

Sometimes;

Often; or

Always.

All right. So hopefully people have had a chance to respond.

[00:28:14]

What Is Brain Health?

So I want to reiterate the American Academy of Neurology position statement on brain health. So brain health is a continuous state of attaining and maintaining the optimal neurologic function that best supports one's physical, mental, and social well-being throughout every stage of life. And what it does is it emphasizes the need to look at brain health, not just something that we take care of in patients who are getting older, but we need to pay attention to it throughout a person's lifespan.

And it also underscores the fact that brain health is really the substrate of our overall well-being. And without brain health, we can't really expect to have optimal physical, mental, and social well-being. So that's why it's been a focus of the American Academy of Neurology and obviously other organizations that take care of people with brain health concerns.

[00:29:07]

Why Is Prevention Important?

So as we just heard, the pathological changes in Alzheimer's disease start well over a decade and sometimes 2 decades before the symptoms are apparent. And most of the causes of cognitive impairment besides Alzheimer's disease also are due to cumulative risk over our lives, whether it be sleep apnea or high blood pressure, diabetes-related vascular, all those things don't happen overnight in a short period of time.

So our brain is going through wear and tear throughout our lives, and we really want to make sure that we are doing as much as we can to prevent these conditions that can affect brain health negatively. And we know that the treatments we have currently, even the new anti-amyloid therapies, as promising as they are, they're not going to reverse the pathological changes and they're at best slowing down the progression of the disease. So it's still secondary prevention.

And if we wait to intervene when the symptoms have already started, then it's not going to be as effective. So prevention is going to be much more effective than intervention after symptom onset. And again, we heard that there are options now that are being looked at for preclinical, which means people who have biomarker positive Alzheimer's disease but don't have symptoms yet. And that's still secondary prevention.

We are not really close to having primary prevention. We should be intervening even before there's amyloid deposition in the brain. And in terms of pharmacological treatments, we don't have anything available. Maybe for people who have dominantly inherited Alzheimer's disease, there are some gene therapy trials that may be effective in people as primary prevention.

But for majority of our patients, the only primary prevention we can really work on is lifestyle management, modifying the modifiable risk factors. So that's going to be the most effective primary prevention.

[00:31:08]

54% Would Want to Know if They Had MCI Due to AD

And there is obviously still a lot of misunderstanding and a lot of, you know, misgivings about Alzheimer's disease. And there's a stigma that kind of gets in the way of our how we want to ideally practice in our clinics. And you know, do patients really want to know if they have the disease or if they're going to be at risk down the road?

And the answer seems like majority of patients would like to know that if they are at a risk of developing or if they have mild cognitive impairment and may go on to develop Alzheimer's disease. And as Dr Sabbagh said earlier, a lot of patients we have are folks who have taken care of or have a history of Alzheimer's disease in the family or have been caregivers for a family member and now are noticing some cognitive changes.

So a lot of people would want to know. And, you know, many people have different reasons to seek the diagnosis. And some of it relates to life planning, some of it relates to getting early treatment, some of it just maybe because they want to know whether they have it or not.

But even without even not considering the treatment aspect of things, people who get diagnosed are much more likely to make changes in their life that make a substantial difference in their overall life management, you know, making sure that they're living in a safe environment or at least planning to do so, simplifying their life, making sure that they're taking care of their financial responsibilities and so forth.

But with what would be considered disease modifying treatments, the antiamyloid therapies, a lot of people that we see in the clinic are now seeking diagnostic evaluations because it may be something that would be available for them.

[00:33:08]

Only 40% Would Talk to Their Doctor About Symptoms Right Away Alzheimer’s Association Survey

But, you know, receiving the diagnosis itself can be tricky for a lot of people. There are still people who would prefer not to know, or at least not bring it up to their doctor. So according to this Alzheimer's Association survey, only about 40% of people surveyed would actually talk to their doctors about symptoms right away. And they again, have a lot of misgivings about what that diagnosis would mean.

So, you know, stigma, how other people might treat them. You know, that it's just sort of a death sentence, that there's nothing that can be done about it. There's no cure. And, you know, a lot of times people are worried about their independence being taken away, driving or somebody else will take over the finances and so forth.

So that is a concern that we hear a lot of people have. And we know that Black and Hispanic Americans are also less likely to want to know, compared to White Americans. And again, Black, Hispanic and Asian Americans are twice as likely to cite a concern for access to healthcare as 1 of the barriers to seeking evaluation.

[00:34:25]

Barriers to Discussing Cognitive Impairment

So what about other barriers in terms of discussing cognitive impairment in a clinical setting? So in this survey of physicians, one third of almost 1000 physicians surveyed said that lack of reimbursement is a barrier. We still see a lot of therapeutic nihilism. I supervised residents, primary care, or internal medicine residents, and a lot of them come out of medical school thinking that there's nothing you can do about Alzheimer's disease.

And again, obviously, that's not true. You know, curing is the goal. But besides that, we can make a big difference in our [inaudible] if we go forward with a positive attitude and we kind of are prepared to handle their concerns.

And another quarter reported the need to address other pressing medical issues, especially in primary care. They have - they may have a lot of different issues, and the brain health concerns does not rise up to that priority level where they would give it the prime time. And so lack of time in a busy clinic is obviously a concern. And some providers are also concerned about patients attitudes.

Again, like I mentioned earlier, if you ask them about their cognitive concerns, will they get upset with me because, you know, they think that I'm trying to take away their driving or privileges. You know, we're really trying to help be proactive. But some patients may think about it. At least the providers think that patients may think about those questions in that way.

And patient factors include patients feeling like it is the primary care doctor's response or primary care or specialist responsibility to identify if there is an issue and bring it up. They’re obviously hesitant to talk about it, bring about it because of shame or stigma. And a lot of times there is a difficulty in patients and caregivers and recognizing what's normal aging from cognitive impairment. And a lot of it is—we see it in our clinics, when they come in late, when things have progressed and when we ask go back into their past, you know, a lot of family members will say, you know, we thought it was just part of normal aging.

All of their friends who are similar to age also complain of similar issues. So that is another barrier.

[00:36:50]

4 Themes in Barriers to Conversations

So the 4 main themes that come up as barriers to conversations is that healthcare providers are hesitant to discuss cognitive concerns. Patients are hesitant to bring up their concerns. There may be social and cultural factors that influence patients and caregivers perception of brain health and cognition that kind of gets in the way.

And finally, there may be not as good communication as we'd like in terms of the evidence we have to guide healthcare professionals. So I hope that things are changing gradually, but as we heard Dr Sabbagh mentioned, you know, there are still a lot of skeptics in terms of the amyloid clearing drugs, in terms of a lot of other aspects related to care in - in our patients.

So I feel like maybe we could do better in terms of communicating the evidence. And hopefully programs like these make an impact.

[00:37:48]

Discussing Brain Health in Routine Clinical Visits

So how do we discuss brain health and routine clinical visits? You know, we want to start conversations with all patients. As I mentioned, even in people with normal cognition, we want to make sure that they're doing the best they can to maintain their cognitive health, their brain health. So we need to frame it as something that is important for their overall health and as part of their normal well checkup.

We need to ask them specifically about memory or cognitive concerns, and we want to be prepared to listen to them carefully and provide a plan, because if they come up with concerns and we don't have a clear plan that we can convey, then that discourages them from pursuing it further. But we want to have a clear plan. We want to provide practical resources to help them make a meaningful impact in their lives.

And we also want to be careful about—or mindful about adapting our conversation to the patient's social and cultural background. We want to address stigma. We want to take it on head on. We don't want to, you know, beat around the bush. We want to make sure that we're not hesitating. And, you know, talking about dementia, Alzheimer's disease, without caging it in, you know, terms that may be vague, just because we're uncomfortable with it and we want to address the knowledge gaps.

A lot of the clinic visit is really educating patients and family members about what's normal aging vs what's pathological. What is dementia vs Alzheimer's disease? Explaining to them that memory loss is not the only thing that we see in dementia or cognitive complaints, you know, because people may have behavioral issues, people may have language based issues, visual spatial issues. So explaining that to patients is important.

And even behavioral impairment could be a precursor to future cognitive impairment. So we want to be clear about that. Differentiating what could happen that cognitive issues can happen in depression and how it differentiates from dementia is also very important.

[00:39:55]

Conversation Starters

So some conversation starters would be asking questions about their personal experiences. And I usually ask them what is their routine like. You know, what do they do with their friends? What do they do with their families? And then ask about whether there's been any change. Like, is there anything that you were able to do last year, 6 months ago, that you're finding it more difficult to do or that somebody else is starting to help you.

And that kind of gives us a sense of what the functional impairment or challenges the person is facing might be. And we always want to ask family members or reliable informants when it comes to cognitive concerns, because a lot of patients with cognitive issues have difficulty gauging whether or not even they have a cognitive concern or if they have some idea that it is present, they may not realize the extent of it, and they may minimize and say, you know, everybody else is having this. This is just normal aging.

And we want to do a thorough evaluation of their risk profile in terms of what are the modifiable risk factors, what are other risk factors that could lead them to have be at a higher risk or causing them to be at a higher risk, and also the resiliency profile, what are they doing right in terms of brain health. You know, are they exercising? Do they have good sleep habits? Do you know what's their diet like?

So that helps us understand their future risk or what things could have contributed if they're already having cognitive issues?

[00:41:18]

Patient-Centered Triad

And it's important to understand for these patients that there is a patient-centered trial. So the patient is the main person that we're trying to evaluate and figure out how we can be of help. The healthcare professional obviously is involved, but we also want to involve the care partner, and we really want them involved early. When the patient is completely independent, we really want a care partner to be able to monitor, to provide us collateral information. Some of the things that the patients may not necessarily bring up as concerns themselves.

[00:41:50]

Alzheimer’s Association Medicare Annual Wellness Visit Cognitive Assessment Algorithm

So this is a helpful algorithm for a primary care setting. And it could also be used in other nonspecialty care settings. So the first should be reviewing their health risk assessment, what kind of observations you've made. If patients have reported any concerns. And if there are no concerns that the patient has reported or that you've noticed, you still want an informant to confirm. And if they're available to confirm and they say, yes, there are no concerns regarding their cognition, then you just follow up at a subsequent visit.

Whereas if there is a concern, whether it's brought forth by the patient himself or herself or that you've noticed some concerns, then you can do a brief structured assessment. And there's not 1 universally accepted, cognitive assessment that you can use as a screening tool, especially in busy nonspecialty care clinics where you may not have a lot of resources to dedicate to this. But a Mini-Cog is very simple and short. GPCOG is similar, very brief assessment, and you can use those to determine whether this needs further evaluation.

And some primary care offices or general neurologists, general geriatrician offices may be equipped to do further assessment with an MMSE or MoCA or SLUMS once they find that there is a concern with the brief test. And you can pair that with informant completed screening tools to determine whether or not the person should be referred to a full dementia evaluation.

[00:43:29]

Alzheimer’s Association DETeCD-ADRD Clinical Practice Guidelines for Primary Care

Before—this is for primary care, where they might be equipped to do a slightly more in-depth dementia evaluation. The Alzheimer's Association Clinical Practice guidelines divided into 7 cores. The first core being establishing a goal for diagnostic process like why are we going through diagnostic process to establish the diagnosis? Do they want future planning? Do they want active treatment? Do they want to go into research? Or maybe they, you know, don't really want to know and they're, you know, okay with not knowing. And then we want to explore that as well.

But it starts with establishing a goal. Then getting a detailed history of their cognitive concerns. And then we want to review what their cognitive concerns are. Behavioral, neuropsychiatric issues, any sensory motor, other neurological issues, obviously, their general health, and then how those things may be affecting their activities of daily living. And similarly biopsychosocial risk factors, developmental risk factors, exam findings. We want to do a structured exam for cognitive assessment, but also make sure that we're doing a general physical, neurologic, psychiatric exam.

And then finally, the diagnostic process involves first establishing whether or not they have a cognitive impairment, whether they're cognitively normal after evaluation, or they have some subjective cognitive complaints, or they have mild cognitive impairment or dementia. And if it's dementia, if it's mild, moderate or severe.

The next main domain of diagnostic evaluation is to identify the syndrome. Are they presenting with more memory related issues or is it language based, or is it a behavioral change? Because that really guides our further etiological diagnostic testing. And that's the third step in the diagnostic formulation is what is the underlying cause of their cognitive syndrome. And is it Alzheimer's disease, is it related to strokes, is it related to Parkinson's disease. So is dementia with Lewy bodies and so on and so forth.

And another important part of this process is to make sure that we can convey the findings, at least the initial findings, in a very clear way and in a compassionate way. Again, it is a very scary process to go for a lot of people, especially with family history, but we want to make sure that we're doing the disclosure in - in an appropriate way.

[00:46:06]

FDA-Approved AD Biomarkers

So there are—so for etiological diagnosis, there are some tests that are available that are approved by the FDA. CSF, testing for Alzheimer's disease biomarkers, looking at A-beta42/40, tau, p tau. Total tau, p tau in different ratios have been available. Now we also have amyloid PET scan that looks at elevated amyloid beta on PET scans that are also available, you know, limited because of availability, cost and so forth.

And now we have blood-based biomarkers that have taken on, especially the primary care field, which, you know, we may need to be very careful about. We want to make sure that it's part of an overall diagnostic process and not a standalone thing that we use to diagnose people.

So the first FDA cleared drug was in May of 2025. And Alzheimer's disease—Alzheimer's Association has established clinical practice guidelines that came out in July of 2025 that the blood tests, with more than 90% sensitivity and more than 75% specificity, can be used for triaging. But for diagnostic confirmation, you have to have something with more than 90% sensitivity and more than 90% specificity.

And I know there are some places that are using blood biomarkers as the only diagnostic test to qualify people for antiamyloid therapies. But at least at our center, we're using amyloid PET scan or CSF.

And in very recent news on October 13th, there was another test that was approved for use in ruling out Alzheimer's disease pathology. And this test specifically was approved for use in primary care. But again, we have to keep in mind that it's not used as a standalone test. It's not used to diagnose people. It's used after somebody who has gone through a detailed cognitive evaluation is thought to be likely to have Alzheimer's disease and doing this test. If it's negative, then it may rule out, because it's considered to have high negative predictive value.

If it's negative, then that may help rule out Alzheimer's disease. But if it's positive, it still would need further evaluation in a specialty clinic.

[00:48:28]

Risk Factors for Dementia: Heath Conditions

So we talked about some risk factors for dementia. These are health conditions that can be risk factors. We talked about it earlier.

[00:48:37]

Risk Factors for Dementia: Medications

Medications can be risk factors. So we want to make sure that we evaluate their medication list very carefully to make sure that we're not using too many anticholinergics, benzodiazepines, hypnotics, estrogen without progestins are—could be considered risk factors. Some platinum-based chemotherapy can lead to Chemo brain but there is not a direct link between those and development of future dementia, but they may cause cognitive issues.

The data on proton pump inhibitors is somewhat inconclusive. But again, like with all medications, we want to make sure that we're using them for the right reasons. And we're balancing the risks and benefits.

[00:49:16]

Risk Factors for Dementia: Social and Other Factors

And obviously there are some other social risk factors that can lead to dementia or be risk factors for dementia. We talked about some of them early - in the early part of the presentation.

[00:49:28]

Clinical Interventions: Lifestyle Modification

So for a healthcare professional, we want to educate people about brain healthy lifestyle. And at every visit, if possible, not when patients bring up concerns. We want to make sure that we give them tools to develop resilience across their lifespan, manage their modifiable risk factors, decrease exposure to environmental risk factors, and then referral to research if people are interested.

[00:49:51]

Health Modifications

So again, these are things that would be done with the primary care provider or specialist as appropriate, but optimizing blood pressure, cholesterol, treating cholesterol levels, hyperlipidemia, dyslipidemia, managing diabetes and blood sugars, treating depression effectively, and then managing optimal weight.

[00:50:12]

Medication Modifications

And again, being very careful about managing medications, evaluating them when people are presenting for cognitive concerns that we're not using anything that's potentially exacerbating their cognitive issues.

[00:50:24]

Sensory Modification

Making sure that their hearing and vision is corrected as optimally as possible, making sure that they're getting evaluated on a regular basis.

[00:50:34]

Lifestyle Modifications

Lifestyle modifications. As we learned from the FINGER and POINTER studies, these are very important tools that anybody can use. And you know, the longer that they've been using these measures, you know, the longer that they've been exercising, the longer they've been adopting a healthy diet, the more, you know, social interactions and learning new things, the - the higher the chances of benefit.

[00:51:01]

Societal Actions

And then some societal policy action would be ensuring quality education for all, making access to medical treatment, including vision, screening, hearing, screening and treatment as much as possible, encouraging helmet use to minimize traumatic brain injuries, you know, figuring out education on adverse effects of smoking, alcohol consumption, and policies to discourage use of those, reducing air pollution and prioritizing age-friendly community environments and housing.

[00:51:36]

Key Takeaways

So the key takeaways would be that brain health in late life, again, is a product of lifelong healthy and lifestyle practices. So we want to focus on it at all ages. Almost half of dementia risk can be attributed to modifiable risk factors. So that's an area where we can really work on primary prevention for dementia, and we want to discuss brain health as part of an overall health with all patients, not just people who express concerns or report symptoms.

And healthcare providers can break through stigma and build trust with patients by bringing up these concerns and, you know, being sensitive, compassionate and informative, when people do have these concerns.

[00:52:22]

Let’s Vote Again!

Okay. And I'll hand it over again to the moderator to go on to the rest of the questions.

Lisa Phipps: Okay. Thank you, Rajeet. Okay. So let's vote again.

[00:52:34]

Posttest 1

So our posttest number 1. A 53-year-old Black man is referred by his primary healthcare provider to your neurology clinic for evaluation of hand tremor. Your initial patient history and review of systems includes several ongoing health issues that the patient considers to be currently well managed. In your discussion with the patient and note back to the primary healthcare provider, which would you recommend to be monitored and closely reevaluated to most likely mitigate his risk of developing cognitive impairment or dementia in the future?

Drinking 4 cups of coffee per day;

History of depression currently treated with an SSRI, a PHQ score of 4 with a range of zero to 27;

Blood pressure in the office of 152 over 85, currently with an ACE inhibitor taking regularly; or

His weight with a BMI of 28, where he exercises regularly for 30 minutes, walking 4 to 5 times weekly.

What do you think? Give you a few seconds to answer that. Okay. And let's see what everybody answered. And it looks like 66. We went from 40% to 66% on C.

[00:54:26]

Posttest 1: Rationale

And Rajeet or Marwan, would you like to kind of discuss the rationale behind that - that answer being the correct answer?

Dr Sabbagh: So we know that some of these things are protective. There's no question about it. But the most sustained and robust data is around blood pressure - aggressive blood pressure management. The coffee data is kind of mixed. We do think mood, but is the patient not depressed? Mood can be an antecedent symptoms of cognitive decline.

And the patient's already adhering to a good health recommendation around exercise. So the - the kind of the gap here is about - is about aggressive management of his blood pressure.

[00:55:10]

Posttest 2

Okay, let's move on to our second post-test question. You have treated a 65-year-old woman for neck pain following a car accident. On follow up visit, her neck symptoms are much improved, but she mentions that she has problems sleeping and on a few occasions has gotten lost while driving and forgotten people's names. She's concerned that these may be early symptoms of Alzheimer's disease. What is the next best step to address her concern during this visit?

Reassure her that occasional memory lapses are normal with aging, but - but order Alzheimer's blood biomarker testing to address her concern;

Perform comprehensive cognitive behavioral assessment before pursuing potential diagnostic testing;

Order cognitive lab - laboratory panel to rule out common medical issues that can affect cognition, neuroimaging to rule out issues such as tumors and infarcts, and APOE4 genetic testing to assess for Alzheimer's disease related e4 status; or

Order a sleep study, but hold off on prescribing a hypnotic.

Which of these would you do? Give everybody a few minutes there. And I believe on pretest we had sort of a bit of an equal choice between B and C there. So let's see what everybody chose on the post test. And it looks like on the post-test, most people - we had a swing towards B, which is the correct answer. So would 1 of the 2 of you like to take this post-test question? Talk about the rationale behind our correct answer B there.

[00:57:09]

Posttest 2: Rationale

Dr Shrestha: Yeah. So, in the thorough assessment in the clinic in terms of assessing whether they even have cognitive issues. Right. So we use a validated tool to establish that they have cognitive impairment before pursuing diagnostic testing.

Now even the first tier diagnostic testing, like, you know, maybe if they have sleep concerns like a sleep study or an MRI or, you know, checking if their thyroid and so forth, it only happens after we do that comprehensive evaluation in the clinic. Getting an Alzheimer's disease biomarker, blood biomarker testing would not be appropriate before we do the cognitive test, and we have to establish that they have cognitive issue first, and especially if you think that their memory issue is normal, then you know it would not warrant a testing. It always has to be with a higher probability that the clinical suspicion that they have Alzheimer's disease and ordering cognitive laboratory panel is appropriate after a comprehensive evaluation suggesting that they might have cognitive concern.

APOE genetic testing really is not recommended as part of the workup unless they are candidates for monoclonal antibody treatment. And again, a sleep study may be appropriate if you think that the clinical history suggests sleep apnea. But that would be after you establish that through clinical or clinical evaluation.

[00:58:34]

Q&A

Lisa Phipps: Thank you. Okay. I'm going to move on to—we had just have a couple of minutes for questions. So I'm going to combine a couple here that really are about - it sounded to me like coordination of care. So we had somebody who said, you know, like, I'm a mental health and psychiatric nurse practitioner. What’s my best approach to assist my patient who comes in with moderate - what looks to me to be moderate to severe cognitive decline, but there's a 6-month wait for me to get them to see a neurologist. And then on the other side of that, we had a neurologist say, “Hey, you know, as a neurologist, do I treat my patient's hypertension or do I refer them back to primary care?”

So maybe a little bit of discussion about how coordination of care and how do we manage these things? What do we tell this mental health nurse practitioner when she's got to wait for her patient who clearly has cognitive decline, but there's a 6-month wait to get to see 1 of you all? And do we tell that neurologist, “Yes, go ahead and treat that hypertension”, or do we refer them back?

Dr Sabbagh: So I will take a shot at that first. I will tell the nurse practitioner that I would do the blood-based biomarkers at a minimum nowadays. So if you know you're dealing - at least you'll know if you're dealing with an Alzheimer process yes or no. You could even go on to do the full evaluation, including the screening for thyroid, hyper - MRI, etc..

For the neurologist, I actually don't. I would - because I'm a neurologist like you. I would say get your primary care physician to manage their blood pressure, but give them specific - specifics about what your parameters are and what you want to achieve. Rajeet?

Dr Shrestha: Yeah. You know, I agree with that. And I would just add that it's a real problem, as we talked during the presentation, that there is a dearth of providers who are equipped to handle this. So I think slowly getting into a point where you are equipping your clinic staff to do some of these screening tests and then familiarizing. So Alzheimer's Association has guidelines for primary care and specialty - specialty as in neurologists psychiatrists.

So if you familiarize yourself with those guidelines, you may have more confidence in managing some of these early stages. But yes, we want early access to specialists. But that is probably not going to be a reality. So I think now that we have resources, it's a matter of triaging. Like Dr Sabbagh said, you know, if somebody is positive in their early stages, then you can prioritize them for specialty care. If they're negative, then you want to look at their risk factors. Maybe have them go back to their primary care for more aggressive modifiable risk factor treatment and so forth.

But yeah coordination care of - coordination of care is key.

Lisa Phipps: Well, thank you so much. We had so many questions come in. We had like 40-something questions come in for this session. We do not have time unfortunately to answer all of them. I want to let everyone out there know on our website, we do have a whole brain health hub. This program, this brain health program is very large, and we have lots of activities for you to look at.

So please make sure you go to our website and look for the brain health hub. Right now we are going to take just a few minutes break. And then we are going to transition to a non-CME talk, Managing Hyperkinetic Movement Disorders from Symptoms and Impacts to Approved Treatment presented by doctors Laxman Bahroo and Marina Ospina. We will start that session at promptly 2:20 PM Eastern, and there will be a link on your screen to take you there.

Once that program is complete, there will be a link to bring you back to our CME program where we will pick up with 2 additional CME sessions, 1 on migraine and 1 on neuropsychiatric symptoms in Alzheimer's disease. I look forward to seeing you all back at the next CME session. Enjoy your short break and click on the link to be transferred to the non-CME session.

[END OF TRANSCRIPT]