ARTICLE IN BRIEF
A longitudinal study is underway to address the underrepresentation of American Indians in research involving cardiovascular and cerebrovascular disease as well as Alzheimer's disease. The principal study authors discuss the logistical, geographic, and cultural challenges involved in conducting the research.
Underserved populations such as American Indians and Alaska Natives are overlooked in a wide array of research studies ranging from observational studies to clinical trials. And that underrepresentation is particularly evident in research on cognitive impairment, Alzheimer's disease, and cerebrovascular disease.
For instance, there are virtually no data on American Indians and Alaska Natives in the National Alzheimer's Coordinating Centers extensive database from about 30 Alzheimer's disease centers scattered throughout the country. The database includes 36,327 people, of whom only 225 (0.6 percent) are American Indian or Alaska Native.
A unique partnership between Washington State University's Partnership for Native Health and the University of Washington Alzheimer's Disease Research Center hopes to change that. Through a funding grant by the National Institute on Aging, American Indians are participating in an ongoing longitudinal study to examine the incidence and long-term effects, risk factors, and links between cardiovascular disease, vascular brain injury, Alzheimer's disease, and cognitive decline.
The long-term goal is to develop tailored interventions for Alzheimer's disease that account for factors such as aging, environment, and medical and family history for Native populations, said study project leader Astrid Suchy-Dicey, PhD, assistant research professor at the Elson S. Floyd College of Medicine at Washington State University in Seattle.
“Cognitive impairment and Alzheimer's disease are not well studied in American Indians and our study is the first large-scale effort to examine Alzheimer's disease in this overlooked community,” said Dr. Suchy-Dicey. “American Indians suffer disproportionately from conditions related to cardiovascular disease and vascular brain injury, but we lack even basic information about prevalence of related outcomes such as Alzheimer's disease or dementia in this population.”
The current gap in information is due to a host of factors. Among them are a lack of validated normative standards upon which to base cognitive test assessments in this group; differences in culture, health perspectives, language, and education; and disparities in access to health care for diagnosis and treatment.
“With better information and answers to some of these questions, we hope to be able to treat or reverse some of the consequences, ultimately supporting longer, healthier lives for all people,” Dr. Suchy-Dicey said.
The study builds on nearly three decades of research in American Indian communities. In 1988, the National Heart, Lung, and Blood Institute launched the Strong Heart Study, the largest and longest epidemiologic research study ever undertaken in American Indians to examine heart disease and risk factors among 4,549 tribal members in parts of Arizona, Oklahoma, North Dakota, and South Dakota. The research team has built strong partnerships with the community members, tribal leaders, partner institutions, hospitals, and the Indian Health Service. Surviving members from the study have participated in several additional research studies, including the Cerebrovascular Disease and its Consequences in American Indians study.
“The community is invested in this research project as evidenced by the tremendous participation, even after more than 30 years,” said principal investigator Dedra Buchwald, MD, professor at the Elson S. Floyd College of Medicine at Washington State University and founding director of the Partnerships for Native Health. “They are involved and devoted to the study partly because the participants receive their own results from the examinations.”
There is a long history of support among the tribes to be active partners in the study, said Everett Rhoades, MD, a member of the Kiowa tribe of Oklahoma and the first Native American director of the Indian Health Service. “I have a number of relatives who have been with the Strong Heart Study since the beginning, as well as many joining later, and they exhibit considerable pride in the fact that they are part of this ongoing study.”
From 2011 to 2013, the landmark study collected data from 1,033 Americans Indians aged 60 and older from 11 communities. Researchers published results in 2017 in the journal Hypertension showing that higher left ventricular mass in middle age was associated with slightly lower general cognitive performance later in life, based on brain magnetic resonance imaging (MRI) assessments and the modified Mini-Mental Status Exam.
Researchers are currently gathering data from a second-round of examinations that, when complete, will include about 450 participants. “We projected that by this point, many of the original participants would be advanced in age, but the cohort is generally healthier than projected, which may allow us to expand our study size,” said Dr. Buchwald. She added that the team is seeking more funding to recruit an additional 240 participants who are still living but not enrolled in the follow-up study. By 2019, the examinations are expected to be completed.
The study team is collecting brain MRI data, and conducting a battery of cognitive and functional tests covering executive function, memory, processing speed, and verbal fluency. Participants undergo a clinical examination and complete several medical, neurological, and family history questionnaires.
From a clinical standpoint, the research team will focus on characterizing vascular brain injury, Alzheimer's disease, and cognitive function in American Indians. From an educational standpoint, it's important to the team to elevate awareness of Alzheimer's disease and dementia in Native communities by providing relevant educational information to community members and providers.
“Ultimately, we hope to address many longstanding obstacles to care by improving research recruitment in the community, determine how many American Indian and Alaska Native people have Alzheimer's disease, identify whether the causes are similar to other populations, and determine whether there are unique challenges and opportunities in managing these conditions in their communities,” said Dr. Suchy-Dicey.
Because many risk factors for cardiovascular disease and vascular brain injury overlap with those of Alzheimer's disease, the researchers decided to collect data relevant to all of these conditions. Dr. Suchy-Dicey pointed out the multiple intersecting and similar risk factors for these conditions, including advanced age, low socioeconomic status, race and ethnicity, and educational level, as well as smoking, obesity, diabetes, hypertension, and dyslipidemia.
“All of these similarities suggest shared or overlapping pathological processes between vascular brain disease and Alzheimer's disease,” she added, “so it's worth studying them simultaneously in the same population to determine to what extent this may be true.”
A long-time member of the steering committee of the Strong Heart Study, Dr. Rhoades said that the findings from the study have provided important information to the communities and to the clinicians who care for American Indian patients. “The present cognitive studies are at the stage of characterizing both cognitive and motor deficiencies that are likely to correlate with certain changes in the brains of participants and will therefore provide valuable information for all population groups.”
Researchers face numerous logistical, geographic, and cultural challenges in conducting a study with Native Americans. Tribes, which are sovereign nations, communities, and community members must be involved at all stages of the research process. This takes considerable time and can lead to the need for longer timelines and more complicated protocols compared with conventional public health research.
“Consider the effort that would be necessary if you were working with multiple sovereign nations, such as a pan-European study,” said Dr. Suchy-Dicey. “This is the same thing because tribes and Native communities are sovereign entities, and so we have to respect their wishes, interests, and obtain permissions when conducting research in partnership with them.”
Yet, tribal and community involvement is critical to fulfilling legal, ethical, and moral obligations, to developing culturally congruent approaches to public health, and to maintaining successful partnerships. “We consider the principles of community-based participatory research to be an equally important element in our work as the principles of scientific and methodological rigor,” said Dr. Buchwald.
Native people and those from other minority groups often face barriers to accessing local, specialized health care for conditions like dementia since specialty centers are often unavailable in remote areas.
Another unique concern for American Indian, Alaska Native, and other minorities and underserved populations revolves around culture, added Dr. Suchy-Dicey.
ADDRESSING CULTURAL DIFFERENCES
Vascular neurologists at Mayo Clinic in Phoenix have witnessed the differences in culture and values among American Indians firsthand. The team is collaborating with Tuba City Regional Health Care Corporation in Tuba City, AZ, that includes Navajo, Hopi, and Southern Paiute tribes. Under the program, Mayo Clinic's neurology department is providing immediate telestroke services to patients who present to local emergency departments with symptoms and signs of an acute stroke.
The team has worked closely with the clinical and administrative leaders of the hospitals in Tuba City to understand the cultural differences of the community and identify the best way to introduce the program to the tribes, said Bart Demaerschalk, MD, MSc, FRCPC, professor of neurology and chair of the cerebrovascular diseases division at Mayo Clinic in Phoenix.
Dr. Demaerschalk added that the community embraces many notable values, including cooperation, group effort, collective strength, passivity, informal courtesy, religion, non-verbal communication, extended family, holistic values, natural time and harmony of body and soul. “We did recognize some skepticism over stroke research, stroke clinical trials, and experimentation, but that is quite understandable. Overall, the relationship with the community of Tuba City and Mayo Clinic has enriched both organizations,” Dr. Demaerschalk said.