BDNF polymorphisms are linked to poorer working memory performance, reduced cerebellar and hippocampal volumes and differences in prefrontal cortex in a Swedish elderly population.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) links learning, memory and cognitive decline in elderly, but evidence linking BDNF allele variation, cognition and brain structural differences is lacking.


METHODS
367 elderly Swedish men (n = 181) and women (n = 186) from Prospective Investigation of the Vasculature in Uppsala seniors (PIVUS) were genotyped and the BDNF functional rs6265 SNP was further examined in subjects who completed the Trail Making Task (TMT), verbal fluency task, and had a magnetic resonance imaging (MRI) scan. Voxel-based morphometry (VBM) examined brain structure, cognition and links with BDNF.


RESULTS
The functional BDNF SNP (rs6265,) predicted better working memory performance on the TMT with positive association of the Met rs6265, and was linked with greater cerebellar, precuneus, left superior frontal gyrus and bilateral hippocampal volume, and reduced brainstem and bilateral posterior cingulate volumes.


CONCLUSIONS
The functional BDNF polymorphism influences brain volume in regions associated with memory and regulation of sensorimotor control, with the Met rs6265 allele potentially being more beneficial to these functions in the elderly.
Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden ; Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South Africa.
Samantha J
SJ
Brooks
Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.
Emil K
EK
Nilsson
Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.
Josefin A
JA
Jacobsson
Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South Africa.
Dan J
DJ
Stein
Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.
Robert
R
Fredriksson
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Lars
L
Lind
Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden.
Helgi B
HB
Schiöth
D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002531:Cerebellum / Q000033:anatomy & histology* / Q000502:physiology; D056344:Executive Function; D005260:Female; D059907:Functional Neuroimaging; D015870:Gene Expression; D056726:Genetic Association Studies; D006624:Hippocampus / Q000033:anatomy & histology* / Q000502:physiology; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008570:Memory, Short-Term; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000033:anatomy & histology* / Q000502:physiology; D011446:Prospective Studies
D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human