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Population Studies and Precision Medicine Research

Because of the accelerated pace of research in recent years, we now know that Alzheimer’s and related dementias are complex conditions that stem from the interplay of genetic, lifestyle, and environmental factors. NIH-supported researchers continue to explore the reasons why some people develop these conditions while others do not, and which genes, lifestyle choices, and other factors seem to be associated with the disease. By studying large, diverse groups of people, investigators can identify which behaviors and lifestyle choices are associated with the development of certain diseases.

NIH’s investments in population studies have already revealed that factors such as sedentary behavior, low socioeconomic status, low level of education, and poor neighborhood may increase the risk of developing dementia. These discoveries, paired with knowledge of genetic and other factors, can be used to design clinical trials to test whether these factors truly confer risk or offer protection. Results from carefully controlled trials could then advance the development of methods for precision diagnosis, prevention, and individualized treatment for Alzheimer’s and related dementias, as has been achieved already for certain cancers. In the future, it is hoped that results from population studies may be used to help researchers develop precise interventions that can address the underlying disease process by tailoring treatment to an individual’s unique disease profile and symptoms.

Some of the recent findings from population studies include:

  • In 2019, an international team of NIH-supported researchers pooled data from more than 3,400 people from multiple observational studies in the U.S., Europe, Canada, and Australia to explore how genetics and family history relate to the age when frontotemporal dementia symptoms develop. In the pooled data, the researchers noted that symptoms developed in people as early as their teen years or as late as their 90s, but the average age varied between 50 and 61, depending on the presence of one of three genetic mutations. Understanding the causes of variation in age of onset could provide important clues about the causes of frontotemporal dementia.
  • A population study of 10,000 British civil servants showed that regularly seeing friends and family during midlife was associated with a lower likelihood of dementia diagnosis in later life. Analysis of the same data source showed that people with better heart health at age 50 may be less likely than those with poor heart health to develop dementia later in life. A third analysis, however, did not find an association between a healthier diet in midlife and a lower risk of dementia 25 years later. A separate analysis of multiple genetic and lifestyle risk factors conducted with UK Biobank Database records from nearly 200,000 participants suggested that choosing healthy lifestyle habits is associated with a lower risk of dementia in cognitively healthy older adults at varying levels of genetic risk.
  • After examining Medicare records for more than 82,000 people who had participated decades earlier in a nationwide high school test that measured personality traits, scholastic aptitude, and interests, researchers discovered that certain personality traits as a teenager may predict dementia risk more than 50 years later.
  • A team of international scientists analyzed data from six comprehensive, community-based observational health studies conducted in the U.S., France, Iceland, and the Netherlands to show that treating high blood pressure is associated with a reduced risk of Alzheimer’s and related dementias.
  • Researchers analyzed 101 older adults, enrolled in the Berkeley Aging Cohort Study, for Alzheimer’s disease-related beta-amyloid and tau protein levels in the brain. They noticed that cognitively healthy adults whose sleep quality declined in middle age were more likely in late life to accumulate amyloid and tau proteins in the brain than those whose sleep quality improved or did not change.
  • A long-term study of 270,000 individuals in Utah suggested that having extended family members with Alzheimer’s, such as having only several third-degree relatives with the disease, increased a person’s risk of developing the disease.
  • The Healthy Cognitive Aging Project, the widest ranging and most representative cohort study on a random subsample of U.S. adults at greatest risk for dementia, released detailed cognitive data for other researchers to use in their work.

Tackling Challenging Health Disparities Through Research

Developing a better understanding of how and why many diseases affect diverse communities in different ways is paramount in our search for treatments and prevention for Alzheimer’s and related dementias. NIH-supported studies in health disparities already have found that the development of Alzheimer’s and related dementias may be influenced by many factors, including race, ethnicity, sex, level of education, geography, and socioeconomic status. For example, research has suggested that:

  • Those who do not graduate from high school are at higher risk.
  • The risk of dementia is highest among African Americans and American Indian or Alaska Natives; intermediate for Latinos, Pacific Islanders, and non-Latino whites; and lowest for Asian Americans.
  • Women are at higher risk of dementia than men.

NIH is committed to supporting studies on risk factors related to health disparities and, through NOT-AG-18-047, is funding more than 60 research projects at universities across the country. Collectively, projects will compare differences in risks for these conditions for men versus women, different racial and ethnic groups, rural communities, socioeconomically disadvantaged neighborhoods, and other societal and individual factors.

Another example of health disparities research is the recent launch of the Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on Recovery (DISCOVERY) study. The goal of this six- year NIH-supported prospective clinical research study is to determine the specific subsets of stroke-related events that cause cognitive impairment and dementia in people who have had a stroke, especially within racial and ethnic minorities who are at higher risk of stroke, cognitive impairment, and dementia.

Recruiting research participants who are representative of the diverse American population is crucial to addressing health disparities, and NIH is investing in a wide range of activities to help investigators reach underrepresented communities. Many of the challenges and opportunities for enhancing recruitment efforts, including the national recruitment strategy and the use of Together We Make the Difference: National Strategy for Recruitment and Participation in Alzheimer’s and Related Dementias Clinical Research, are described in the Prevention and Treatment Research section.

For a more in-depth look at the research implementation milestones in this area, including progress and accomplishments, visit

Find a list of references for this section in the PDF version.

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