title: Effect of BDNF Val66Met polymorphism on regional white matter hyperintensities and cognitive function in elderly males without dementia.
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.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Brain Connectivity Lab, Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chu-Chung
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Mu-En
authors.initials: ME
authors.lastname: Liu
authors.affiliation: Brain Connectivity Lab, Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taiwan.
authors.forename: Kun-Hsien
authors.initials: KH
authors.lastname: Chou
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Yang
authors.affiliation: Brain Connectivity Lab, Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chen-Jee
authors.initials: CJ
authors.lastname: Hong
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: tsai610913@gmail.com.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Brain Connectivity Lab, Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taiwan. Electronic address: cplin@ym.edu.tw.
authors.forename: Ching-Po
authors.initials: CP
authors.lastname: Lin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Aged; Brain-derived neurotrophic receptor; Cognition; Polymorphism; White matter hyperintensities