Causal relationship between multiparameter brain MRI phenotypes and age: evidence from Mendelian randomization

Area of Science:

• Neuroimaging
• Genetics
• Gerontology

Background:

• Aging is associated with various brain structural changes, including cortical atrophy, white matter integrity alterations, white matter hyperintensities, and cerebral microbleeds.
• Understanding the causal relationship between chronological age and these brain health indicators is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the causal effect of age on multiparameter brain imaging features indicative of brain health.
• To explore the relationship between age and cortical volume, white matter integrity, white matter hyperintensities, and cerebral microbleeds.

Main Methods:

• Utilized two-sample Mendelian randomization to assess the causal relationship between age and brain health phenotypes.
• Analyzed genetic data related to age and brain imaging features using the inverse-variance weighted model.
• Validated findings using heterogeneity and horizontal pleiotropy analyses.

Main Results:

• Age is causally linked to increased white matter hyperintensity volumes (β = 0.151).
• White matter integrity is causally deteriorated in specific tracts, including the inferior cerebellar peduncle, cerebral peduncle, superior fronto-occipital fasciculus, and limbic system fibers.
• Decreased cortical thickness was observed in frontal and temporal regions; cerebral microbleeds showed no significant association with aging.

Conclusions:

• Aging poses a significant threat to brain health, driving cortical atrophy, particularly in frontal lobes.
• Age-related white matter degeneration is evident, characterized by increased hyperintensities and compromised white matter integrity, especially around the hippocampus.
• These findings highlight the detrimental impact of aging on brain structure and integrity.