Dopamine D1 receptors and age differences in brain activation during working memory

被引:93
作者
Backman, Lars [1 ]
Karlsson, Sari [1 ]
Fischer, Hakan [1 ]
Karlsson, Per [2 ]
Brehmer, Yvonne [1 ]
Rieckmann, Anna [1 ]
MacDonald, Stuart W. S. [1 ,3 ]
Farde, Lars [2 ]
Nyberg, Lars [4 ,5 ]
机构
[1] Karolinska Inst, Aging Res Ctr, SE-11330 Stockholm, Sweden
[2] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, SE-11330 Stockholm, Sweden
[3] Univ Victoria, Dept Psychol, Victoria, BC V8W 2Y2, Canada
[4] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden
[5] Umea Univ, Dept Integrat Med Biol, Umea Ctr Funct Brain Imaging, S-90187 Umea, Sweden
基金
瑞典研究理事会;
关键词
Aging; Dopamine; D-1; receptors; fMRI; Load-dependent BOLD response; Multimodal brain imaging; PET; Spatial working memory; PREFRONTAL CORTEX; D1; RECEPTORS; PET ANALYSIS; SCH; 23390; BINDING; DECLINE; INVOLVEMENT; TRANSPORTER; MODULATION; CAPACITY;
D O I
10.1016/j.neurobiolaging.2009.10.018
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [C-11] SCH23390 to determine dopamine D-1 receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load > lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D-1 BP in caudate and DLPFC. Statistical control of caudate and DLPFC D-1 binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:1849 / 1856
页数:8
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