Age-related decline in brain resources modulates genetic effects on cognitive functioning

被引：192
作者：
Lindenberger, Ulman [1 ]
Nagel, Irene E. [1 ]
Chicherio, Christian [1 ,2 ]
Li, Shu-Chen [1 ]
Heekeren, Hauke R. [1 ,3 ]
Baeckman, Lars [1 ,4 ]
机构：
[1] Max Planck Inst Human Dev, Berlin, Germany
[2] Univ Geneva, Fac Psychol & Educ Sci, Geneva, Switzerland
[3] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany
[4] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden
来源：
FRONTIERS IN NEUROSCIENCE | 2008年 / 2卷 / 01期
基金：
瑞典研究理事会;
关键词：
genes; aging; resources; cognition; dopamine;
D O I：
10.3389/neuro.01.039.2008
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging. Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008), who reported that the effects of the Catechol-O-Methyltransferase (COMT) gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF) gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed. (150 of 150 words)
引用
收藏
页码：234 / 244
页数：11
相关论文
共 109 条
[1]   The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades [J].
Alexander, D. M. ;
Williams, L. M. ;
Gatt, J. M. ;
Dobson-Stone, C. ;
Kuan, S. A. ;
Todd, E. G. ;
Schofield, P. R. ;
Cooper, N. J. ;
Gordon, E. .
BIOLOGICAL PSYCHOLOGY, 2007, 75 (03) :229-238
[2]   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
[3]   KIBRA genetic polymorphism influences episodic memory in later life, but does not increase the risk of mild cognitive impairment [J].
Almeida, O. P. ;
Schwab, S. G. ;
Lautenschlager, N. T. ;
Morar, B. ;
Greenop, K. R. ;
Flicker, L. ;
Wildenauer, D. .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2008, 12 (5A) :1672-1676
[4]   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
[5]  
Backman L, 1998, PSYCHOL AGING, V13, P267
[6]   Rate of cognitive decline in preclinical Alzheimer's disease:: The role of comorbidity [J].
Bäckman, L ;
Jones, S ;
Small, BJ ;
Agüero-Torres, H ;
Fratiglioni, L .
JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES, 2003, 58 (04) :P228-P236
[7]  
Bäckman L, 2000, AM J PSYCHIAT, V157, P635
[8]  
BACKMAN L, 1999, HDB AGING COGNITION, P499
[9]   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
[10]   Lifespan psychology: Theory and application to intellectual functioning [J].
Baltes, PB ;
Staudinger, UM ;
Lindenberger, U .
ANNUAL REVIEW OF PSYCHOLOGY, 1999, 50 :471-507
12345678910