Heart and Brain: A Clearer Connection

Published research is now backing up what would appear to many to be a clear heart and brain connection. As more of this research is circulated, it could have a direct impact on how neurologists practice medicine and on how neurologists and primary care physicians treat patients and interact with each other.What's good for the heart is good for the brain, and conversely, what's bad for the heart is bad for the brain. That may seem obvious. As neurologist Stanley N. Cohen, MD, of Cedars-Sinai Medical Center in Los Angeles, put it: "It doesn't take a rocket scientist to tell you that if you take good care of yourself, you'll be in better shape should you be lucky enough to live longer."Science, however, has only recently begun to lay out the case. The message emerging amid a flurry of epidemiologic papers, most from large-scale, multicenter, population-based studies, is clear: cardiovascular risk factors can affect cognitive function in middle age and lead to dementia in later life. "What's bad for the heart is bad for the brain," said Rachel A. Whitmer, PhD, a researcher at Kaiser Permanente Division of Research in Oakland, Calif. "We kind of knew it before and now it's been well documented, and now it's a really important message."A recent study by Whitmer and colleagues, the results of which were published in January in Neurology,1 was based on a review of 8845 members of the Kaiser Permanente Medical Care Program of Northern California who had participated in voluntary multiphasic health checkups in San Francisco and Oakland between 1964 and 1973, when the participants were 40 to 44 years old. "We sought to determine the predictive value of cardiovascular risk factors-high cholesterol, blood pressure, body weight and body mass index, diabetes, hypertension, and smoking-in midlife on risk for developing late-life dementia in a large, multiethnic cohort of men and women followed for an average of 27 years. All those in our study had equal access to health care, and that is something relevant and exciting in terms of these findings," she said. "Our results suggest that the presence of multiple cardiovascular risk factors at midlife-independent of age, race, sex, and education-substantially increases risk for dementia in old age."Although previous research had reported an association between the risk of cardiovascular disease and stroke in later life and the loss of high cognitive function and risk of dementia,2,3 "this is the first study to look at midlife risk factors and an outcome in late life," Whitmer said. Moreover, other studies have shown that people with cardiovascular risk factors in middle age show greater cognitive decline than people without such risk factors.4,5 In the Third National Health and Nutrition Survey (NHANES III),5 conclusions were drawn for persons aged 30 to 59.Currently, a team including Jacob S. Elkins, MD, a neurologist at the University of California, San Francisco (UCSF), is looking in the other direction too. They reviewed records of a population of middle-aged adults from the Atherosclerosis Risk in Communities (ARIC) study 6 to determine to what extent cognitive function can predict future cardiovascular events, such as first-time stroke and heart disease. "We kind of flipped the hypothesis on its head a little bit," said Elkins. His colleague, neurologist S. Claiborne Johnston, MD, PhD, also at UCSF, elaborated: "We said, 'Okay, if the brain is really sensitive to cardiovascular risk factors, then maybe cognitive function in midlife is predictive of having a heart attack or stroke down the line.'" The results of their study are pending publication in Neurology."We think declines in cognitive function can be related to vascular injury in the brain," Elkins said. After analyzing the cognitive test results of 12,096 middle-aged participants in the ARIC study who had no history of stroke or coronary heart disease at the time of cognitive testing, and then assessing the follow-up data for 6 to 7 years, that's exactly what they found. "Even after we accounted for/adjusted our analysis on the typical cardiovascular risk factors-blood pressure, diabetes, smoking, cholesterol-the people who were performing low on their cognitive tests were at considerably higher risk for having stroke or heart attack," Elkins said. "The size of that risk is very comparable to things we commonly measure, like left ventricular hypertrophy and low HDL cholesterol."All this research underscores what physicians have always believed to be true, researchers said. "Stroke is the second leading cause of dementia, so the fact that there is more dementia associated with vascular risk factors really is not a terrible surprise," said Cohen of Cedars-Sinai. Added neurologist David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn: "Basically, cardiovascular disease in midlife is a risk factor for subsequent dementia in late life-period. What we need to be able to do is prevent dementia, because once it's established, it's very costly, and treatment is not very rewarding. That is our challenge in the field. The good news is that cardiovascular disease in midlife is a modifiable risk state. Treatments for hypertension, high blood pressure, diabetes, and hypercholesterolemia are all available interventions, so we have the power to intervene right now in 2005."RETHINKING HOW NEUROLOGISTS THINKDoes that mean neurologists will be venturing into the turf of primary care physicians and internists? That, no doubt, will be debated. In any event, changing clinical practice will take time. "We have to begin with first identifying the potential areas where we could intervene and then prove interventions do make a difference," said Johnston. The impact of this research now, he added, is that "it gives doctors yet another reason to prescribe drugs that control these risk factors, and it gives the patients another reason to take them. But that will mostly be driven by primary care physicians and by the neurologists who are advising them or teaching them."In most clinical settings today, neurologists don't see patients soon enough to address these issues, Cohen pointed out. "You really do need to make these changes in the 40s, and neurologists generally don't see patients when they're 40, but when they're 75 and forgetting to turn the gas off at the house. The reality now is that, if somebody comes into your office with migraine headache when 35, we focus on treating the migraine rather than the lifestyle [complications]. If the neurologist does get involved [in cardiovascular risk factors], it's going to tick off the internist, who's going to say, 'That's my domain.'"Knopman recalled the period right after World War II up to the 1980s, when the incidence of stroke declined dramatically, presumably because of improved treatment of hypertension. "It wasn't the neurologists who did it; it was primary care docs who were treating people for hypertension," he said.Traditionally, treatment of midlife cardiovascular disease has not been what neurologists do. However, every physician who sees a patient should be more aware and more vocal, said neurologist John Castaldo, MD, of Lehigh Valley Hospital in Allentown, Pa. "Patients come into the hospital and are seen by a cardiologist, neurologist, and often when they leave it is with elevated blood pressure and cholesterols or [they're] not even checked, and nothing is said to them about discontinuing smoking, because every doctor says it's not my job, it's the job of primary care. But then the primary care physician sees a patient and thinks, 'Gee, if the cardiologist and the neurologist didn't think it was important, maybe it's not so important.' We're sending mixed messages," Castaldo said. "If you don't jump in and address cholesterol when someone has a stroke, then you're not reducing stroke and you're not part of the team. This is really a part of every doctor's domain. The family doctor has to say it. The cardiologist has to say it. The neurologist has to say it. And the exercise physiologist working with them ought to say-how are you doing with your cholesterol? Have you stopped smoking?"Internist Eric G. Tangalos, MD, who is professor of medicine and chair of the Division of Community Internal Medicine at the Mayo Clinic in Rochester, agreed. "I don't see it as a turf battle at all. I think everybody wants to do the best by their patients. We want to do the right thing. That is our job. If it takes a team effort, that's OK, because these [risk factors] have to be addressed."In fact, that's exactly what's happening at the Mayo Clinic, as it is at many other medical centers. Tangalos, for example, has frequent interactions with Knopman with regard to patients, and they function as a team. "We work together in a collaborative process and we share an electronic record and we share a research agenda," explained Tangalos. "I am very much in favor of a team approach to get these [risk factors] taken care of. Where the neurologist's talents end, then mine might begin or where mine might end, the neurologist's may begin. You've got to put the package together on the care of the patient overall."For those neurologists who may still have some reluctance in getting involved with a patient's blood pressure or other vascular risk factors, communication is key, these physicians agreed. The undeniable take-home message of the heart-brain disease connection presents an opportunity for neurologists to advise primary care physicians about the additional need to treat patients for these risk factors and to converse with and advise their own patients, Johnston said. "Neurologists end up being conduits for information to primary care docs in the area of neurosciences, so it's very likely that a lot of primary care docs are going to hear about this kind of thing from neurologists at their hospital," he said.Ultimately, the findings point to a broader, more fundamental change in neurology. "This link between cardiovascular disease and brain disease will have a more pervasive impact on neurologic practice in years to come, because it suggests the pendulum is swinging from the pure degenerative, nonvascular approach to Alzheimer's disease and dementia, back toward the recognition that vascular diseases do play a role in dementing illness," Knopman said."You can't pigeonhole the disease any longer," expounded Tangalos. "Alzheimer's is not pure. Vascular disease is not pure. The evidence is mounting that there's a lot of overlap," meaning many patients suffer from mixed dementia-a combination of the pure nerve degenerative process that is Alzheimer's disease and vascular dementia. "That's probably much more common than currently established," added Cohen.While the dementia profile/diagnosis is revealing itself to be more complex than initially believed, when it comes to treatment, Tangalos suggested, "it makes it easier, because you're going to treat all conditions. No physician can be fearful of saying 'I'm not sure it's Alzheimer's or vascular.' If there's any evidence [dementia] is there, don't shy away from treating blood pressure, and don't shy away from treating diabetes."Added Castaldo, "I believe the answer is going to be in addressing atherosclerosis not as a specialty problem, but a generic problem. It affects the heart, the brain, and the legs. It affects primary care, internal medicine, renal medicine, cardiology, and neurology. It affects all of us and we all have to jump in and do our part in educating the patients about managing those risk factors aggressively.""The heart of this story," said Cohen, "is that we need to get involved in primary prevention early."A Question Of HowThe first signs that the pendulum has swung are already here. "When people are seen for memory loss or cognitive complaints, a lot of doctors now are starting to appreciate how much vascular risk factors may be contributing to that and how more aggressive treatment of those risk factors would have the potential to prevent a worsening of cognitive impairment over time," Elkins said. "A neurologist wouldn't necessarily think that, for patients with early signs of Alzheimer's disease, [they] should be that concerned about what their blood pressure is, but they actually do need to pay much more attention to that."Although neurologists and other physicians still don't know how aggressively these cardiovascular risk factors should be treated, most neurologists aren't thinking about aggressive approaches in relation to maintaining high cognitive function, researchers agreed. "When patients are seen now for early signs of mild cognitive impairment, neurologists may think about prescribing medication like Aricept, but they don't necessarily think as aggressively as they should about controlling things like blood pressure or diabetes. There actually are some studies that show that lowering blood pressure in the old can slow cognitive decline,7,8 so there are some data out there that support being more aggressive about these things," added Johnston.Gary Small, MD, spokesman for the Alzheimer's Foundation, and director of the Center on Aging at the University of California, Los Angeles, added the other major factor: "It's not just medication, but lifestyle that's critically important," he said. "It is common sense, but I think where people realize that cardiovascular risk factors are bad for the heart, they're not there yet with the fact that these risk factors are also bad for the brain," he said. What neurologists can easily do is reinforce the message. "We can inform our patients and encourage them to live a healthy lifestyle," said Small.That's where the going gets tough. After all, pulling these risk factors into check almost always requires significant change in behavior. "You cannot just tell a patient, 'take this medicine and come back in a couple of months and we'll check your blood pressure.' It just doesn't work," said Castaldo. "It's not the patient's fault and it's not the doctor's fault, it is the complexity of the disease and the multiple people treating it."Castaldo has come up with a model that has been up and running and returning remarkable results for 9 years. After conducting a survey in his area, he found that while physicians "paid lip service" to preventive care, they found it too complex to do in the setting of a doctor's office. So, he secured a $5 million grant and teamed with the doctors and nurses in his hospital and created a workable model of a freestanding facility "designed to show the effectiveness of prevention intervention" with patients who had a stroke, heart attack, or claudification event. Of 500 total patients, 250 chose to enroll in the aggressive intervention and attend a 12-week education and training program where they learned everything from the importance of blood pressure control and cholesterol to how to exercise, shop for healthy foods, and cook a tasty, low-fat meal. Each patient was followed for 3 years. Unpublished data from the study to date, said Castaldo, showed that the aggressive intervention group had 50% fewer deaths and 50% fewer ischemic events and that their quality of life "soared."Small said that a movement-"a memory fitness movement," as he described it-is afoot within the public at large. "People are beginning to realize they have more control than they think in terms of staving off Alzheimer's disease and vascular dementia," he said. Small promotes a 2-week program that combines healthy diet with physical conditioning, memory training, and stress reduction techniques.IN THE PIPELINE AND BEYONDMeanwhile, research continues. Johnston, Elkins, and colleagues are studying the effectiveness of incorporating brief cognitive tests into routine physical examinations. Such tests are used for Alzheimer diagnoses, "but not for a regular cardiac checkup, yet they do seem to pick up some of the pathology of cognitive decline," Elkins pointed out. "What we're suggesting in this paper is that these cognitive tests are cheap, fairly easy to administer, can be done fairly quickly, and they seem to add a lot of prognostic information, so they may be able to be incorporated into checkups."The same group is also in the midst of the follow-up to their 2004 study, the Cardiovascular Health Study, in which they are investigating stroke risk factors and loss of high cognitive function.2 "With [the study], we have decent follow-up, but the all people start out over the age of 65, and we were curious about behaviors that begin in midlife," Johnston explained. "So in a study that is kind of parallel to what Rachel [Whitmer] has done, we're gathering additional data to look at midlife predictors of high cognitive function. We want to better characterize cognitive function in older people, and we're also looking at genetic factors."The goal in regard to the genetics component is to understand which factors are involved in protecting the brain from vascular injury and which are associated with allowing the brain to recover more effectively once injury occurs, Elkins elaborated. "There seems to be a lot of differences in people in terms of how susceptible they are to things like high blood pressure and diabetes. If we can quantify that better, then we can use that information to identify protective factors-either genetic or behavioral-and then that could suggest new avenues for prevention," he said.Whitmer and colleagues, meanwhile, have reexamined the Kaiser Permanente multiphasic data on the cardiovascular treatments that patients were given and how these treatments influenced outcome.In addition, she said, "we are seeking funding to look at subtypes of dementia."Neurologists and patients alike are excited about this research, not only because treatments for cardiovascular risk factors are now at hand but also because the research offers such hopeful prospects for late life. "Consider that it's just been in the last 20 years that we have begun to better understand the impact of the sun on skin aging," Johnston offered by way of analogy. "We know now that skin aging is not just inevitable-some aspects of it are, but we do have some control. We're having a similar revelation about aging. Yes, the brain does get older and it doesn't work as well as we get older, but what all this research suggests is that a lot of the things that make it not work well are things that are within our control," he said.This growing body of evidence indicates that "there are so many things we can change about what we had called 'normal aging,'" said Johnston. "Just thinking that maybe not all aspects of cognitive decline are inevitable-that maybe we can potentially slow the normal decline so that we could maintain very high cognitive functioning until very old age and each live our lives out like George Burns-that for us was the most revealing aspect of all this. If we all had brains as healthy as his was, we could live much fuller lives."REFERENCES1. Whitmer RA, Sidney S, Selby J, et al. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology. 2005;64:277-281.2. Elkins JS, O'Meara ES, Longstreth WT Jr, et al. Stroke risk factors and loss of high cognitive function. Neurology. 2004;63:793-799.3. Kivipelto M, Helkala EL, Laakso MP, et al. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ. 2001;322:1447-1451.4. Knopman D, Boland LL, Mosley T, et al. Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology. 2001;56:42-48.5. Pavlik VN, Hyman DJ, Doody R. Cardiovascular risk factors and cognitive function in adults 30-59 years of age. Neuroepidemiology. 2005;24:42-50.6. The ARIC investigators. The Atherosclerosis Risk in Communities (ARIC) study: design and objectives. Am J Epidemiol. 1989;129:687-702.7. Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003;163:1069-1075.8. Forette F, Seux ML, Staessen JA, et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med. 2002;162:2046-2052.AJS RAYL is a freelance writer in Malibu, Calif.---Sidebar-Unhealthy Food Consumption Not AllowedScience's validation of the link between heart/cardiovascular risk factors and brain/cognitive decline and dementia raises issues and poses challenges at the personal level as well as at the broader social level. With just a little imagination, one can envision a future in which everyone will not be created equal and in which acceptance into insurance plans-even jobs-will be based on one's profile of cardiovascular risk factors as well as on one's genetic "map."That, for now, is when. Right now, however, persons need to become aware of the dangers to their health, and neurologists have a role to play in getting the message out, said Gary Small, MD, spokesman for the Alzheimer's Foundation and director of the Center on Aging at the University of California, Los Angeles. "The more I study it, the more adamant I become," he said. "We should do the studies. We should start the intervention programs, and start to help people now."The prescription will be a tough pill for many patients to swallow. "Clinicians will get frustrated," Small predicted. "Patients come in and they don't want a prescription that says: 'Start walking 20 minutes after dinner every night.' They want a pill. When you're talking about future prevention and long-term effects, it is hard to motivate people. But you can have an impact. You can put messages on television. 'This is your brain on drugs' with the egg frying in the pan, for example, was a very powerful and effective strategy for the 'war on drugs.' And you can legislate it, as California has with prohibiting smoking in enclosed public places. So I think there are things we can do," he said.For others, the good of the many is stomping on-or at least restricting-the freedoms of the individual. That raises ire-and political issues. Legislating "no smoking" ordinances has proved difficult despite the hard evidence that smoking causes cancer. To date, only a handful of states have adopted such ordinances for all public places. Legislating how someone eats, however, would be impossible, contended David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn. "You say, 'eat healthy.' Does that mean you are going to make me eat vegetables and fruits? No way! The question is, how much can authorities demand change in lifestyle and behavior simply because they're paying the bills. I live in Minnesota, a very progressive state, but our state does not require motorcyclists to wear helmets, and when those [cyclists] get into motor vehicle accidents, it costs hundreds of thousands of dollars, so this is a political issue as much as it is a health issue," he said.Others are skeptical that such public education may result in wide-ranging social change because of the individual's inability or lack of desire to change set behaviors. Making lifestyle changes requires commitment from both patient and physician, particularly when such changes apply to food addictions and cigarette smoking."I would love to be able to say that 'Yeah, we're going to make a difference.' The reality is, people don't change," said neurologist Stanley N. Cohen, MD, of Cedars-Sinai Medical Center in Los Angeles. "I did some research a couple of years ago at the Veterans Administration [Medical Center], looking at a stroke population of 100 patients. I went to the records and looked to see how well their risk factors were controlled 3 months before the stroke and then again 12 months after the stroke to see if their risk factors were in better control, and almost nobody had anything in better control than before. Many patients initially have good intentions, and then it's probably a combination of the patient not being motivated [enough to] change [his] ways and the doctors not having enough time to follow up."Inevitably, everyone-practicing physicians and patients alike-has to be motivated. In the end, those who help themselves will reap the rewards, while the others will never be helped, no matter what their neurologist says.