In the past, research suggested a connection between cerebral small-vessel disease, a common condition, and the risk of dementia. However, a new study now presents conclusive evidence of a causal relationship, identifying it as a significant vascular factor.
Research conducted in part by The University of Texas Health Science Center at San Antonio (UT Health San Antonio) reveals that the most prevalent feature of cerebral small-vessel disease observed in brain magnetic resonance imaging is a primary vascular factor linked to the risk of dementia.
The outcomes of this major international study highlight the importance of this feature, known as white matter hyperintensity (WMH) burden, in strategies aimed at preventing dementia.
“Our findings offer substantial evidence that WMH is a key vascular factor associated with dementia risk,” stated Muralidharan Sargurupremraj, PhD, an assistant professor at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio. “They also support the use of WMH as a marker for clinical trials aimed at preventing dementia by managing vascular risks.”
Sargurupremraj served as the primary and co-corresponding author for the research paper titled “Genetic Complexities of Cerebral Small Vessel Disease, Blood Pressure, and Dementia,” published on May 22 in JAMA Network Open, a monthly open-access medical journal by the American Medical Association.
The study underscores that as life expectancy rises, dementia is projected to affect 75 million individuals globally by 2030, making the development of strategies to prevent or delay its onset a critical public health concern. It is widely recognized in the scientific community that most dementia cases, including Alzheimer’s disease, stem from a combination of vascular and neurodegenerative issues.
Cerebral small-vessel disease is believed to be the primary underlying factor contributing to cognitive decline and dementia, with nearly half of dementia cases demonstrating characteristics of both Alzheimer’s and cerebral small-vessel disease pathologies, as noted in the study.
While previous observational studies indicated a link between increased risk of stroke and dementia with a higher burden of white matter hyperintensities, causal evidence was scarce. White matter hyperintensities are areas in the brain that appear brighter in T2-weighted magnetic resonance imaging scans.
In the new study, researchers were able to establish a causal relationship between vascular traits and Alzheimer’s disease by utilizing genetic instrument variable analyses known as Mendelian randomization. This method utilizes the natural randomization of genetic alleles to examine how genetic variation in modifiable exposures impacts disease risk.
Through a two-year analysis up to July 24, 2022, and incorporating Alzheimer’s disease genome-wide association studies involving up to 75,000 European dementia cases, they discovered evidence of a causal connection between a higher WMH burden and an elevated risk of the disease, while adjusting for the effects of pulse pressure.
The study also stressed the significance of combining various epidemiological approaches and data types, as well as considering the limitations of instrumental variable analyses when investigating the impact of vascular traits on late-onset illnesses like dementia.
“Given that vascular disease is a modifiable factor contributing to dementia risk, our findings hold broad implications for strategies to prevent Alzheimer’s and dementia,” concluded Sargurupremraj.
The researchers suggest that future studies should explore whether their findings can be applied to non-European populations.
Among the other institutions and entities involved in the study are the University of Bordeaux (France); University of Washington; University of Michigan; University of Tartu (Estonia); Erasmus MC University Medical Center, Rotterdam (Netherlands); Boston University and the National Heart, Lung, and Blood Institute Framingham Heart Study; Icelandic Heart Association (Iceland); Washington University, St. Louis; University of Oxford (United Kingdom); Department of Public Health, Bordeaux (France); University of Pittsburgh; University of Lille (France); Radboud University, Nijmegen (Netherlands); Universidad Adolfo Ibañez, Santiago (Chile); University of Iceland (Iceland); Oslo University Hospital, Oslo (Norway); Norwegian University of Science and Technology; Imperial College London (United Kingdom); National Institute on Aging; and Bordeaux University Hospital (France).
UT Health San Antonio plays a key role in San Antonio’s $44.1 billion health care and biosciences sector and stands as the largest academic research institution in South Texas with an annual research portfolio of $413 million.
