Effect of BDNF Val66Met polymorphism on regional white matter hyperintensities and cognitive function in elderly
Chu-Chung Huang1, Mu-En Liu2, Kun-Hsien Chou3
1Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Brain Connectivity Lab, Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
Abstract:
White matter lesions, also termed White Matter Hyperintensities (WMH), on T2-weighted MR images, are common in the elderly population. Of note, their presence is often accompanied with cognitive decline and the risk of dementia. Even though previous brain ischemia and WM lesion studies have been conducted and indicated that brain-derived neurotrophic factor (BDNF) might protect against neuronal cell death, the interaction between regional WMH volume and the BDNF Val66Met polymorphism on the cognitive performance of healthy elderly population remains unclear. To investigate the genetic effect of BDNF on cognitive function and regional WMH in the healthy elderly population, 90 elderly men, without dementia, with a mean age of 80.6 ± 5.6 y/o were recruited to undergo cognitive tests, structural magnetic resonance imaging (MRI) scans, and genotyping of BDNF alleles. Compared with Met homozygotes, Val homozygotes showed significantly inferior short-term memory (STM) performance (P = .001). A tendency toward dose-dependent effects of the Val allele on WMH volume was found, and Val homozygotes showed larger WMH volume in the temporal (P = .035), the occipital (P = .006), and the global WMH volume (P = .025) than others. Significant interaction effects of BDNF genotypes with temporal WMH volume on STM performance was observed (F1,89 = 4.306, P = .041). Val homozygotes presented steeper negative correlation compared to Met carriers. Mediation analysis also demonstrated that WMH in temporal, limbic, and subcortical regions might mediate the relationship between BDNF's genetic effect and STM performance. Our findings supported the hypothesis that the BDNF Val66Met polymorphism may affect susceptibility to regional WMH volume and such genotype-by-WMH interaction effect is correlated with cognitive decline in non-demented elderly males, in which the Met allele plays a protective role.
Insights
The brain-derived neurotrophic factor (BDNF) Val66Met gene variant influences white matter lesion (WMH) volume and short-term memory in elderly men. The Met allele may offer protection against cognitive decline associated with WMH.
Area of Science:
- Neuroscience
- Genetics
- Gerontology
Background:
- White matter lesions (WMH) are common in the elderly and linked to cognitive decline and dementia risk.
- Brain-derived neurotrophic factor (BDNF) may protect neurons, but its interaction with WMH and cognition in healthy elderly is unclear.
Purpose of the Study:
- To investigate the genetic effects of BDNF Val66Met polymorphism on cognitive function and regional WMH in healthy elderly men.
- To explore the interaction between WMH volume and BDNF genotype on cognitive performance.
Main Methods:
- Recruited 90 non-demented elderly men (mean age 80.6 years).
- Conducted cognitive tests, structural MRI scans, and BDNF Val66Met genotyping.
- Analyzed regional WMH volume and its correlation with cognitive performance and genetic factors.
Main Results:
- Val homozygotes showed significantly poorer short-term memory (STM) compared to Met homozygotes (P = .001).
- Val homozygotes had larger global, temporal, and occipital WMH volumes.
- Significant interaction between BDNF genotype and temporal WMH volume affected STM; WMH mediated the BDNF-STM relationship.
Conclusions:
- The BDNF Val66Met polymorphism affects susceptibility to regional WMH volume in elderly men.
- Genotype-by-WMH interactions correlate with cognitive decline, with the Met allele showing a protective role.
