In a groundbreaking study, researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have conducted the largest genome-wide association study on dementia, encompassing various causes. The study revealed a significant overlap in genetic risks associated with neurodegeneration, vascular factors, and cerebral small-vessel disease.
Genome-wide association studies play a crucial role in identifying genes linked to specific diseases or traits by analyzing the entire genome of a large group of individuals. In this study, the researchers analyzed a dataset of 800,597 individuals, including 46,902 cases of all-cause dementia and 8,702 cases of vascular dementia.
“Dementia is a complex disease with contributions from Alzheimer’s disease and vascular dementia pathologies. However, most studies focus solely on Alzheimer’s disease,” explained Bernard Fongang, PhD, from the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio. “Our study on all-cause dementia revealed a significant genetic overlap with vascular dementia.”
Fongang, who is also affiliated with the departments of biochemistry and structural biology, and population health sciences at the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio, served as the corresponding author for the study titled “A genome-wide association meta-analysis of all-cause and vascular dementia,” published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The study was attributed to the Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) consortium, an international collaboration of cohorts focused on the genetics of vascular cognitive impairment and dementia.
Two Distinct Dementias
The study highlighted that Alzheimer’s disease is typically considered the most common form of dementia, followed by vascular dementia. Despite their differences in clinical presentation, recent evidence suggests a significant role for brain vascular damage in cognitive impairment across various dementia subtypes.
The presence of stroke or extensive cerebral vascular disease characterizes the diagnosis of vascular dementia, with atherosclerosis and arteriolosclerosis as underlying pathologies. The study emphasized the importance of brain vascular damage as a key mechanism for cognitive impairment in dementia, acting in conjunction with other neurodegenerative pathologies.
With most genetic studies focusing on Alzheimer’s disease, Fongang’s team conducted a comprehensive analysis of all-cause dementia and explored the genetic overlap with vascular dementia. The diverse dataset included individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the Alzheimer’s Disease Genetics Consortium (ADGC), the European Alzheimer Disease Biobank (EADB), and the UK Biobank (UKBB) with varying ancestries.
Replication of known genetic variants associated with Alzheimer’s disease in all-cause dementia and vascular dementia further confirmed the link between genetic risks and the development of these conditions. Functional analysis revealed a shared genetic risk for all-cause dementia with neurodegeneration, vascular risk factors like hypertension and diabetes, and cerebral small vessel disease.
Essentially, genetic variants known to be associated with Alzheimer’s disease were identified as risk factors for both all-cause dementia and vascular dementia, highlighting the genetic complexity of these conditions.
“Our study expands the current understanding of dementia genetics by exploring genetic variants and pathways associated with all-cause dementia and vascular dementia. We provided additional evidence supporting the involvement of vascular mechanisms in the pathogenesis of dementia,” Fongang stated.
The researchers stressed the importance of validating these findings in diverse populations beyond European ancestries to enhance the generalizability of the results. UT Health San Antonio, as the largest academic research institution in South Texas, continues to drive innovation and research in various fields, including dementia studies, with an annual research portfolio of $413 million.
