TY - JOUR
T1 - Effect of BDNF Val66Met polymorphism on regional white matter hyperintensities and cognitive function in elderly males without dementia
AU - Huang, Chu Chung
AU - Liu, Mu En
AU - Chou, Kun Hsien
AU - Yang, Albert C.
AU - Hung, Chia Chun
AU - Hong, Chen Jee
AU - Tsai, Shih Jen
AU - Lin, Ching Po
N1 - Funding Information:
This study was supported in part by National Science Council of Taiwan ( NSC 100-2628-E-010-002-MY3 ; NSC 101-2314-B-075-040 ; NSC 101-2314-B-075-041-MY3 ; NSC 100-2911-I-008-001) , National Health Research Institute ( NHRI-EX100-9813EC ), Taipei Veterans General Hospital ( VGHUST100-G1-4-1 ), Cheng-Hsin hospital ( 99F167CY02 ), and a grant from Ministry of Education, Aim for the Top University Plan. The authors also acknowledge MR support from the MRI Core Laboratory of National Yang-Ming University, Taiwan.
PY - 2014/1
Y1 - 2014/1
N2 - 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±5.6y/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.
AB - 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±5.6y/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.
KW - Aged
KW - Brain-derived neurotrophic receptor
KW - Cognition
KW - Polymorphism
KW - White matter hyperintensities
UR - http://www.scopus.com/inward/record.url?scp=84888020120&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2013.09.027
DO - 10.1016/j.psyneuen.2013.09.027
M3 - Article
C2 - 24275008
AN - SCOPUS:84888020120
SN - 0306-4530
VL - 39
SP - 94
EP - 103
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 1
ER -
