Combining genetic risk with cardiovascular disease risk factors — such as high LDL cholesterol, obesity, and hypertension — may predict who is more likely to develop dementia, according to a new study led by UC San Francisco.
This expanded view is more hopeful for those worried about dementia. While genes account for about half the risk of developing dementia and cannot be changed, the other half is determined by factors like social isolation, uncorrected hearing loss, and physical inactivity, which can be addressed.
“With Alzheimer’s disease, you may have several vascular diseases involved, like hypertension and diabetes,” said corresponding author Shea Andrews, PhD. “If you make lifestyle changes and improve control of illnesses like these, you could reduce the amount of overall damage to the brain, potentially delaying or even preventing symptoms.”
The study, which was funded by the National Alzheimer’s Coordinating Center’s (NACC) New Investigator Award, used data from about 3,500 adults who had contributed to the NACC and the Alzheimer’s Disease Neuroimaging Initiative.
The average age of the people in the cohort was 75. None had dementia at the start of the six-year study but approximately 1 in 4 had mild cognitive impairment (MCI), which usually precedes it. By the study’s end, 1 in 7 had died and 1 in 4 of the surviving participants with normal cognition or MCI had progressed to dementia.
The researchers found that risk was impacted by four factors:
- Having a parent or sibling with dementia
- Inheriting at least one copy of a gene variant called APOE4 that is strongly associated with Alzheimer’s
- Having a high polygenic risk score that reflects many smaller genetic effects
- Having a high cardiovascular risk score
The researchers also looked for rare mutations associated with early-onset Alzheimer’s but none of the participants had them.
The more risk factors a person had, the more likely they were to develop dementia. One factor increased the risk by 27%; two increased it by 83%; three by 100%; and four increased the risk fivefold.
“We haven’t had a precision medicine approach to help patients reduce their modifiable risks before, because Alzheimer’s couldn’t be diagnosed or treated,” Andrews said. “But now we have treatments that may slow disease progression, particularly in its earliest stage, which can be identified with a blood test or a specialized type of brain imaging called a PET scan.”
He added that genetic data relating to dementia is expected to be more readily available in a few years.
“An optimal scenario for using this data might involve a patient sharing their concerns about dementia with their family doctor following a parent’s diagnosis,” he said. “The physician would then discuss the genetic data and collaborate with them on ways to lower modifiable risks.”
A heightened awareness of the role of non-genetic factors could help those who are at increased risk of developing dementia.
“I think focusing on what patients can control gives them agency and ownership,” said Kristine Yaffe, MD, who has been at the forefront of investigating the role of modifiable risk factors in dementia and is the paper’s senior author. “This allows them to take proactive steps, rather than wait for symptoms to emerge.”
Other Authors: Paulina Tolosa-Tort, PhD, Caroline Jonson, PhD, Jennifer S. Yokoyama, PhD, from UCSF; Brian Fulton-Howard, PhD, and Alan Renton, PhD, from Icahn School of Medicine at Mount Sinai.
Funding: National Alzheimer’s Coordinating Center New Investigator Award (5U24AG072122), National Institutes of Health (R35AG071916 and U19AG069701). For further funding sources and disclosure, please see the study
Read the study
Journal: The Journal of the Alzheimer’s Association: The role of genomic-informed risk assessments in predicting dementia outcomes
About UCSF Psychiatry and Behavioral Sciences
The UCSF Department of Psychiatry and Behavioral Sciences and the Langley Porter Psychiatric Institute are among the nation's foremost resources in the fields of child, adolescent, adult, and geriatric mental health. Together they constitute one of the largest departments in the UCSF School of Medicine and the UCSF Weill Institute for Neurosciences, with a focus on providing unparalleled patient care, conducting impactful research, training the next generation of behavioral health leaders, and advancing diversity, health equity, and community across the field.
UCSF Psychiatry and Behavioral Sciences conducts its clinical, educational, and research efforts at a variety of locations in Northern California, including the UCSF Nancy Friend Pritzker Psychiatry Building; UCSF Langley Porter Psychiatric Hospital; UCSF Health medical centers and community hospitals across San Francisco; UCSF Benioff Children’s Hospitals in San Francisco and Oakland; Zuckerberg San Francisco General Hospital and Trauma Center; the San Francisco VA Health Care System; UCSF Fresno; and numerous community-based sites around the San Francisco Bay Area.
About the UCSF Weill Institute for Neurosciences
The UCSF Weill Institute for Neurosciences, established by the extraordinary generosity of Joan and Sanford I. "Sandy" Weill, brings together world-class researchers with top-ranked physicians to solve some of the most complex challenges in the human brain.
The UCSF Weill Institute leverages UCSF’s unrivaled bench-to-bedside excellence in the neurosciences. It unites three UCSF departments—Psychiatry and Behavioral Sciences, Neurology, and Neurological Surgery—that are highly esteemed for both patient care and research, as well as the Neuroscience Graduate Program, a cross-disciplinary alliance of nearly 100 UCSF faculty members from 15 basic-science departments, as well as the UCSF Institute for Neurodegenerative Diseases, a multidisciplinary research center focused on finding effective treatments for Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, and other neurodegenerative disorders.
About UCSF
The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.
