Summary: New research shows that dementia risk is best predicted by combining genetic vulnerability with cardiovascular disease markers, revealing a more precise and actionable way to identify who is most likely to develop the condition. While genes such as APOE4 and family history contribute heavily, equally powerful are modifiable factors like hypertension, obesity, and diabetes.
People with multiple overlapping risks were significantly more likely to progress from normal cognition or mild cognitive impairment to dementia during the six-year study. These results underscore the importance of addressing vascular and lifestyle factors early, offering a pathway toward prevention even for those with elevated genetic risk.
Key Facts:
- Combined Risks Amplify Danger: Each additional genetic or cardiovascular risk factor substantially increases the likelihood of progressing to dementia.
- Modifiable Factors Matter: Hypertension, diabetes, obesity, and lifestyle behaviors can offset or counteract part of an individual’s genetic vulnerability.
- Early Action Is Critical: Interventions during the earliest stages—when cognition is still intact—may delay or prevent symptoms.
Source: UCSF
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.”
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.
Key Questions Answered:
A: They create an additive risk profile in which multiple factors sharply increase the chance of developing dementia.
A: Family history, APOE4 status, polygenic risk score, and cardiovascular risk all significantly contribute.
A: Yes—improving vascular health and addressing modifiable behaviors may delay or even prevent symptoms.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this Alzheimer’s disease, genetics, and CVD research news
Author: Suzanne Leigh
Source: UCSF
Contact: Suzanne Leigh – UCSF
Image: The image is credited to Neuroscience News
Original Research: Open access.
“The role of genomic-informed risk assessments in predicting dementia outcomes” by Paulina Tolosa-Tort et al. Alzheimer’s & Dementia
Abstract
The role of genomic-informed risk assessments in predicting dementia outcomes
INTRODUCTION
By integrating genetic and clinical risk factors into genomic-informed dementia risk reports, healthcare providers can offer patients detailed risk profiles to facilitate understanding of individual risk and support the implementation of personalized strategies for promoting brain health.
METHODS
We constructed an additive score comprising the modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (mCAIDE), family history of dementia, apolipoprotein E (APOE) genotype, and an Alzheimer’s disease (AD) polygenic risk score in National Alzheimer’s Coordinating Center (NACC) and Alzheimer’s Disease Neuroimaging Iniative (ADNI), and assessed its association with progression to all-cause dementia.
RESULTS
A total of 81% of participants had at least one high-risk indicator for dementia, with each additional risk indicator linked to a 34% increase in the hazard of dementia onset.
DISCUSSION
We found that most participants in memory and aging clinics had at least one high-risk indicator for dementia. Furthermore, we observed a dose-response relationship where a greater number of risk indicators was associated with an increased risk of incident dementia.
