Human aging magnifies genetic effects on executive functioning and working memory

被引：185

作者：

Nagel, Irene E. ^{[1
,2
]}

Chicherio, Christian ^{[1
]}

Li, Shu-Chen ^{[1
,2
]}

von Oertzen, Timo ^{[1
]}

Sander, Thomas ^{[3
]}

Villringer, Arno ^{[2
,4
,5
]}

Heekeren, Hauke R. ^{[1
,2
,4
,5
]}

Backman, Lars ^{[1
,2
,6
]}

Lindenberger, Ulman ^{[1
,2
]}

机构：

[1] Max Planck Inst Human Dev, D-14195 Berlin, Germany

[2] Berlin Neuroimaging Ctr, Berlin, Germany

[3] Max Delbruck Ctr Mol Med, Berlin, Germany

[4] Charite, Dept Neurol, D-13353 Berlin, Germany

[5] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany

[6] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden

来源：

FRONTIERS IN HUMAN NEUROSCIENCE | 2008年 / 2卷

基金：

瑞典研究理事会;

关键词：

genes; dopamine; executive functions; prefrontal cortex; aging;

D O I：

10.3389/neuro.09.001.2008

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We demonstrate that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. We assess two common Val/Met polymorphisms, one affecting the Catechol-O-Methyltransferase (COMT) enzyme, which degrades dopamine (DA) in prefrontal cortex (PFC), and the other influencing the brain-derived neurotrophic factor (BDNF) protein. In two tasks (Wisconsin Card Sorting and spatial working memory), we find that effects of COMT genotype on cognitive performance are magnified in old age and modulated by BDNF genotype. Older COMT Val homozygotes showed particularly low levels of performance if they were also BDNF Met carriers. The age-associated magnification of COMT gene effects provides novel information on the inverted U-shaped relation linking dopaminergic neuromodulation in PFC to cognitive performance. The modulation of COMT effects by BDNF extends recent evidence of close interactions between frontal and medial-temporal circuitries in executive functioning and working memory.

引用

页数：8

共 71 条

[1] PARALLEL ORGANIZATION OF FUNCTIONALLY SEGREGATED CIRCUITS LINKING BASAL GANGLIA AND CORTEX [J].

ALEXANDER, GE ;

DELONG, MR ;

STRICK, PL .

ANNUAL REVIEW OF NEUROSCIENCE, 1986, 9 :357-381

[2] DOPAMINE D2 RECEPTORS IN NORMAL HUMAN BRAIN - EFFECT OF AGE MEASURED BY POSITRON EMISSION TOMOGRAPHY (PET) AND [C-11] RACLOPRIDE [J].

ANTONINI, A ;

LEENDERS, KL .

ALZHEIMERS DISEASE: AMYLOID PRECUSOR PROTEINS, SIGNAL TRANSDUCTION, AND NEURONAL TRANSPLANTATION, 1993, 695 :81-85

[3]

Bäckman L, 2000, AM J PSYCHIAT, V157, P635

[4]

BACKMAN L, 1999, HDB AGING COGNITION, P499

[5] The correlative triad among aging, dopamine, and cognition:: Current status and future prospects [J].

Backman, Lars ;

Nyberg, Lars ;

Lindenberger, Ulman ;

Li, Shu-Chen ;

Farde, Lars .

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 2006, 30 (06) :791-807

[6] Lifespan psychology: Theory and application to intellectual functioning [J].

Baltes, PB ;

Staudinger, UM ;

Lindenberger, U .

ANNUAL REVIEW OF PSYCHOLOGY, 1999, 50 :471-507

[7] Emergence of a powerful connection between sensory and cognitive functions across the adult life span: A new window to the study of cognitive aging? [J].

Baltes, PB ;

Lindenberger, U .

PSYCHOLOGY AND AGING, 1997, 12 (01) :12-21

[8] Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function:: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls [J].

Barnett, J. H. ;

Jones, P. B. ;

Robbins, T. W. ;

Mueller, U. .

MOLECULAR PSYCHIATRY, 2007, 12 (05) :502-509

[9] Prefrontal-hippocampal coupling during memory processing is modulated by COMT Val158met genotype [J].

Bertolino, Alessandro ;

Rubino, Valeria ;

Sarnbataro, Fabio ;

Blasi, Giuseppe ;

Latorre, Valeria ;

Fazio, Leonardo ;

Caforio, Grazia ;

Petruzzella, Vittoria ;

Kolachana, Bhaskar ;

Hariri, Ahmad ;

Meyer-Lindenberg, Andreas ;

Nardini, Marcello ;

Weinberger, Daniel R. ;

Scarabino, Tommaso .

BIOLOGICAL PSYCHIATRY, 2006, 60 (11) :1250-1258

[10] The catechol-O-methyltransferase polymorphism:: Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes [J].

Bilder, RM ;

Volavka, J ;

Lachman, HM ;

Grace, AA .

NEUROPSYCHOPHARMACOLOGY, 2004, 29 (11) :1943-1961

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