For cardiologist Annabelle Volgman, MD, combating stroke and the cognitive decline that all too often follows is a deeply personal matter. When her mother, now 87, suffered a stroke in her mid-60s, her life began an irreversible slide and gave Volgman, medical director of the Rush Heart Center for Women in Chicago, a firsthand look at the devastation that cerebrovascular and neurodegenerative diseases can unleash on whole families.
“My mother was an incredibly energetic and amazing woman, but after her stroke she began to lose her balance, personality, memory and her wonderful spirit,” Volgman recounts. “It completely changed her and the dynamics of our family, and as a cardiologist of 30 years, I now work as hard as I can to prevent that from happening to other families.”
As part of that mission, Volgman, who also is a professor of medicine and senior attending physician at Rush University Medical Center, is a member of a team of cardiologists, neurologists and psychologists exploring the connections between heart disease and dementia. What they’ve uncovered in their studies is that women, who comprise two-thirds of all people clinically diagnosed with Alzheimer’s disease, tend to have different kinds of coronary disease than men, namely more small vessel or microvascular disease in the heart arteries and possibly in the brain, which may contribute to their disproportionate rate of dementia (J Am Heart Assoc 2019;8:e013154).
Volgman and colleagues also have developed some practical approaches to addressing the complex issue of heart and brain health. For example, when Volgman noticed a number of years ago that some of her patients were complaining of memory loss (and blaming it on the medications she was prescribing), she brought in a dementia neurologist colleague to work alongside her at the Rush Heart Center for Women so that certain patients could be expertly and conveniently screened by both specialists during the same visit.
In the future, she points out, a team approach will be critical for the field of cardiology. “We can’t do it with just one doctor—we need a neurologist, an endocrinologist and a nutritionist working together to properly care for these patients, especially the ones with comorbidities,” she says.
The intersection of cardiovascular disease and dementia is hardly new turf. More than 100 years ago, Alzheimer’s was described by scientists as a disease of the blood vessels of the brain, and accumulating evidence since then has pointed to the overlap of vascular risk factors—including high blood pressure, diabetes, elevated cholesterol, obesity and smoking—and cognitive decline. Midlife hypertension alone is estimated to be responsible for 425,000 additional cases of Alzheimer’s disease in the U.S. annually (JAMA Neurol 2017;74:1246-54).
Yet the linkage between coronary disease and cognitive dysfunction remains inconclusive, with the scientific and medical communities historically divided into separate camps. Advanced technologies and determined investigators, however, are starting to unravel the century-old mystery and open the door to urgently needed new therapeutic approaches to both diseases.
One of those investigators is Valentin Fuster, MD, PhD, chief of cardiology and director of the Zena and Michael A. Wiener Cardiovascular Institute at Mount Sinai in New York City. With the help of MRI and PET imaging, Fuster and his research team have raised the possibility that one contributor to Alzheimer’s disease could be the result of blood clots occluding the tiny arteries of the brain, leading to microinfarcts and cognitive dysfunction, including memory loss. “For many years, people thought that Alzheimer’s was a disease just of the cells of the brain,” he explains. “But we’re now able to see for the first time the correlation between the risk factors that affect the large arteries that supply blood to the heart and perhaps thrombosis and the tiny vessels of the brain.”
Another study powered by MRI and led by researchers in the Netherlands found that stiffening of the aorta—perhaps not coincidentally the vessel that acts as a coupling device between heart and brain perfusion—may lead to small vessel disease and heart failure, which in turn can contribute to early cognitive decline and vascular dementia (Circulation 2017;135:2178-95). This study further reported that treatment of heart failure may actually reverse cognitive decline as shown in patients who underwent cardiac transplantation, ventricular resynchronization therapy or physical training to improve heart function.
COMMON RISK FACTORS
Cardiovascular disease and dementia also may have a demographic component. Vascular risk factors that manifest in mid-life appear to be most strongly associated with later-life cognitive decline, according to a study of nearly 16,000 people ages 44 to 66 from four U.S. communities who were examined over decades (JAMA Neurol 2017;74:1246-54). The strongest risk factor was diabetes, linked to a 77 percent greater risk of having dementia over the next 25 years, followed by hypertension, prehypertension and smoking, all at 40 percent, notes Rebecca Gottesman, MD, PhD, professor of neurology and epidemiology at Johns Hopkins University, and lead author of the study.
Gottesman’s work has further shown that people with coronary risk factors like high cholesterol, high blood pressure, diabetes, obesity and smoking are more likely to accumulate beta amyloid, a telltale marker of Alzheimer’s disease, in the brain. The more risk factors present, the greater the likelihood this pernicious protein will appear. “All these factors emphasize the need for people to act before they become a health threat,” she maintains. “Middle age is a critical window for people to recognize risk factors and, even more importantly, take steps to reduce the chances of cognitive dysfunction later on through steps like physical activity, proper diet and smoking cessation.”
To be truly successful, Gottesman hastens to add, that effort also will require the active participation and even a new mindset by physicians. “There hasn’t been much collaboration between cardiologists and neurologists,” she points out. “I’m a stroke neurologist and it’s only been in the last few years the field of dementia has really recognized the importance of vascular risk factors and that they are a potential path to prevention.” More important than ever, in her view, will be collaboration among cardiologists, primary care doctors and physicians who specialize in diagnosing and treating dementia. “We need to approach this disease from multiple angles going forward,” she declares.
That thought is echoed by Volgman, who believes internists in particular should be more actively involved in ferreting out dementia since they routinely deal with older patients. Some even have experience conducting mini-mental exams for detecting potential cognitive issues—simple exams that ask patients to recall three things, for example, or to draw the face of a clock. “It takes a little bit of time,” she acknowledges, “but perhaps we should all be doing these for certain patients, especially those with cognitive concerns.” (See sidebar below.)
Martha Gulati, MD, MS, chief of cardiology at the University of Arizona College of Medicine in Phoenix, would take the early detection strategy a significant step further. She sees in the not-so-distant future the advent of “cardio-brain or cardio-neurology clinics,” much like the cardio-oncology and cardio-obstetrics clinics that now exist. “We need to be thinking about how we can better care for these patients by integrating the various components of that care,” she says. “We as a medical community are not very good at prevention. We’re more about sick care than health care. I wonder, if we were better at reducing risk factors and maintaining the overall health of patients if we would have fewer cases of Alzheimer's and cardiovascular disease.”
That the various clinical disciplines may finally be coalescing is evidenced by the commitment of $43 million last year by the American Heart Association and the Paul G. Allen Frontiers Group to bridge vascular and brain science through innovative research. The alliance is aimed at accelerating new initiatives designed to shed light on how to better detect, treat and prevent age-related cognitive impairment.
THE ROLE OF CARDIOVASCULAR MEDICATIONS
An intriguing question to those in the field is which cardiovascular medications, if any, might have the ability to delay or even prevent the onset of Alzheimer’s and other dementias. While the definitive answer will require a great deal of additional research, some rays of light are visible. A study led by Marta Cortes-Canteli, PhD, of the Spanish National Center for Cardiovascular Research, and Fuster at Mount Sinai, for example, showed in mouse models that anticoagulation with dabigatran, a clinically approved oral direct thrombin inhibitor with a low risk of intracerebral hemorrhage, prevented memory decline and cerebral hypoperfusion in the brain. Long-term treatment with dabigatran also significantly reduced amyloid plaques and toxic fibrin deposition, which is upregulated early on in Alzheimer's disease (J Am Coll Cardiol 2019;74:1910-23).
Patients with atrial fibrillation also may be able to reduce the risk of dementia by taking stroke prevention medications, according to an expert consensus statement developed through an international collaboration of heart rhythm societies (Heart Rhythm 2018;15:e37-60). The document explains that AFib is associated with a more than twofold risk of silent strokes that, over time, may accumulate and contribute to cognitive impairment. Thus, preventing strokes through oral anticoagulation drugs may do double-duty by also reducing the risk of dementia. Interestingly, the guidance cautions physicians to suspect cognitive impairment if their patient’s appearance or behavior changes—if, for example, appointments are missed. In such cases, family members should be consulted and, if suspicions are confirmed, an objective assessment of the patient’s cognitive function should be undertaken.
The story around statins and dementia remains murky. Since 2012, statin labels have warned that some people have reported memory loss or confusion while taking the medications, though there is limited clinical evidence to prove a causal relationship. In fact, Johns Hopkins researchers who reviewed randomized controlled trials and prospective studies following participants for 25 years concluded there is some evidence that long-term statin use may actually protect against dementia by reducing blockages in vessels that carry blood to the brain (Mayo Clin Proc 2013;88:1213-21). More recently, a prospective observational study of elderly Australians found no difference in the rate of memory or cognitive decline of elderly statin-users compared to never-users (J Am Coll Cardiol, online Nov. 18, 2019).
“The data is very unclear when it comes to the effects of statins on dementia,“ acknowledges Volgman, “and I don’t believe there was sufficient evidence for the FDA’s black-box warning that statins may cause dementia. The good news about statins is that they’re anti-inflammatory, and I think if we can get the right patients on these drugs, we’ll see a decline in both strokes and dementia.”
WHEN TO PERFORM PROCEDURES ON DEMENTIA PATIENTS
Underscoring the complexity of issues that frontline physicians routinely confront in the cardio-dementia space is one that’s as much ethical as it is clinical. To wit, whether to perform cardiovascular tests, procedures or surgeries on a patient with dementia, and to what extent the patient’s ability to make informed decisions should factor into the cardiologist's plans for advanced care.
Fuster crystalizes the issue this way: “We might prolong life, but if the brain is not working, what are we achieving?” Still, he notes that he has indicated cardiac surgery on patients with cognitive dysfunction, including those with Down syndrome, and took satisfaction when it contributed to an improved quality of life.
For Gulati, who heads up clinical heart care at the Heart Institute at Banner Health in Phoenix, the decision to proceed with surgery on dementia patients is a gnawing challenge that draws as much on the art as it does the science of medicine. “We want to always do right by the patient,” she says, elaborating that if a patient is unable to participate in decision-making due to a cognition deficit or inability to speak, then the physician must look for guidance in advanced medical directives and/or from family members or associates with power of attorney. Patients who are in earlier stages of cognitive impairment and still functional may pose less of a challenge, she adds, but still raise vexing questions that can only be answered through an insightful reading of the patient sitting in front of the doctor. “Dementia has its own unique scale,” she allows.
The opportune time to confront the critical issues around dementia and vascular disease is not later in life, but earlier on, when something positive can still be done about it, says Fuster. “For me, the real challenge of the next 20 years will be the brain—identifying cognitive dysfunction much earlier in people and getting them to embrace healthier lifestyles,” he asserts. “This is much more important to people than we ever thought before. No one wants to experience cognitive dysfunction in their lifetime.”
See the related article: Evidence mounts for deep learning’s potential to help fight Alzheimer’s