PMID- 17973920
OWN - NLM
STAT- MEDLINE
DCOM- 20080625
LR  - 20131121
IS  - 1601-183X (Electronic)
IS  - 1601-183X (Linking)
VI  - 7
IP  - 4
DP  - 2008 Jun
TI  - Brain-derived neurotrophic factor polymorphism Val66Met influences cognitive 
      abilities in the elderly.
PG  - 411-7
AB  - A functional brain-derived neurotrophic factor (BDNF) gene polymorphism 
      (Val66Met) that alters activity-dependent secretion has previously been reported 
      to influence cognitive functioning. A large proportion of these reports suggest 
      that the Met allele, which results in reduced secretion of BDNF, impairs 
      long-term memory as a direct consequence of its influence on hippocampal function 
      but has little influence on working memory. In contrast, other studies have found 
      that the Met allele can also play a protective role in certain neurological 
      conditions and is associated with improved non-verbal reasoning skills in the 
      elderly suggesting effects that appear disease, domain and age specific. We have 
      investigated six haplotype-tagging single nucleotide polymorphisms (SNPs) using a 
      cohort of 722 elderly individuals who have completed cognitive tests that 
      measured the domains of fluid intelligence, processing speed and memory. We found 
      that the presence of the Met allele reduced cognitive performance on all 
      cognitive tests. This reached nominal significance for tests of processing speed 
      (P = 0.001), delayed recall (P = 0.037) and general intelligence (g) (P = 0.008). 
      No association was observed between cognitive tests and any other SNPs once the 
      Val66Met was adjusted for. Our results support initial findings that the Met 
      allele is associated with reduced cognitive functioning. We found no evidence 
      that the Met allele plays a protective role in older non-demented individuals. 
      Magnetic resonance imaging data collected from a subgroup of 61 volunteers showed 
      that the left and right hippocampus were 5.0% and 3.9% smaller, respectively, in 
      those possessing the Met allele, although only a non-significant trend was 
      observed.
FAU - Miyajima, F
AU  - Miyajima F
AD  - Centre for Integrated Genomic Medical Research, University of Manchester, 
      Manchester, United Kingdom.
FAU - Ollier, W
AU  - Ollier W
FAU - Mayes, A
AU  - Mayes A
FAU - Jackson, A
AU  - Jackson A
FAU - Thacker, N
AU  - Thacker N
FAU - Rabbitt, P
AU  - Rabbitt P
FAU - Pendleton, N
AU  - Pendleton N
FAU - Horan, M
AU  - Horan M
FAU - Payton, A
AU  - Payton A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071031
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Amino Acid Substitution/genetics
MH  - Atrophy/genetics/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/chemistry/*genetics
MH  - Cognition Disorders/*genetics/*metabolism/physiopathology
MH  - Cohort Studies
MH  - DNA Mutational Analysis
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genetic Testing
MH  - Genotype
MH  - Hippocampus/*metabolism/pathology/physiopathology
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Memory/physiology
MH  - Memory Disorders/genetics/metabolism
MH  - Methionine/genetics/metabolism
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Neuropsychological Tests
MH  - Polymorphism, Genetic/*genetics
MH  - Valine/genetics/metabolism
EDAT- 2007/11/02 09:00
MHDA- 2008/06/26 09:00
CRDT- 2007/11/02 09:00
PHST- 2007/11/02 09:00 [pubmed]
PHST- 2008/06/26 09:00 [medline]
PHST- 2007/11/02 09:00 [entrez]
AID - GBB363 [pii]
AID - 10.1111/j.1601-183X.2007.00363.x [doi]
PST - ppublish
SO  - Genes Brain Behav. 2008 Jun;7(4):411-7. doi: 10.1111/j.1601-183X.2007.00363.x. 
      Epub 2007 Oct 31.