The role of the striatal dopamine transporter in cognitive aging

Erixon-Lindroth, Nina; Farde, Lars; Wahlin, Tarja-Brita Robins; Sóvágó, Judit; Halldin, Christer; Bäckman, Lars

doi:10.1016/j.pscychresns.2004.09.005

Cited by 219 publications

(165 citation statements)

References 72 publications

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“…As is true with corresponding research on patients with HD (Ba¨ckman et al, 1997;Lawrence et al, 1998), markers of D 1 , D 2 , and DAT binding in both the caudate and the putamen show strong relationships to each other as well as to cognitive performance (Wang et al, 1998;Yang et al, 2003;Volkow et al, 1998b;Ba¨ckman et al, 2000;Mozley et al, 2001;Erixon-Lindroth et al, 2005).…”

Section: Generality Versus Specificitymentioning

confidence: 53%

“…As noted above, agerelated cognitive deficits are especially pronounced in tasks that require active (executive) stimulus processing (Ba¨ck-man et al, 1999(Ba¨ck-man et al, , 2001Kausler, 1991;Salthouse, 1992;Lo¨vde´n and Lindenberger;West, 1996). We also reviewed evidence that DA markers are strongly related to performance on executively demanding tasks (Volkow et al, 1998b;Ba¨ckman et al, 2000;Erixon-Lindroth et al, 2005). Along these lines, a DA account of cognitive aging holds that an important reason for the large agerelated differences observed in executively demanding tasks is that such tasks require excessive DA release to be successfully performed (Mattay et al, 2003).…”

Section: Da Release During Cognitive Task Performancementioning

confidence: 79%

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The correlative triad among aging, dopamine, and cognition: Current status and future prospects

Bäckman

Nyberg

Lindenberger

et al. 2006

Neuroscience & Biobehavioral Reviews

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706

563

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The brain neuronal systems defined by the neurotransmitter dopamine (DA) have since long a recognized role in the regulation of motor functions. More recently, converging evidence from patient studies, animal research, pharmacological intervention, and molecular genetics indicates that DA is critically implicated also in higher-order cognitive functioning. Many cognitive functions and multiple markers of striatal and extrastriatal DA systems decline across adulthood and aging. Research examining the correlative triad among adult age, DA, and cognition has found strong support for the view that age-related DA losses are associated with age-related cognitive deficits. Future research strategies for examining the DA-cognitive aging link include assessing (a) the generality/specificity of the effects; (b) the relationship between neuromodulation and functional brain activation; and (c) the release of DA during actual task performance. r

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Section: Generality Versus Specificitymentioning

confidence: 53%

Section: Da Release During Cognitive Task Performancementioning

confidence: 79%

The correlative triad among aging, dopamine, and cognition: Current status and future prospects

Bäckman

Nyberg

Lindenberger

et al. 2006

Neuroscience & Biobehavioral Reviews

Self Cite

706

563

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“…These studies have documented the association between cognition and measures of presynaptic as well as postsynaptic striatal DA. In general, reduced DA uptake, decreased DA binding, and decreased tonic DA release in the caudate and putamen are associated with worse performance on tasks requiring set shifting, planning, working memory, and sustained attention (ie executive skills) in healthy adults (Erixon-Lindroth et al, 2005;Mehta et al, 2004;Mozley et al, 2001;Verhoeff et al, 2001;Volkow et al, 1998). These findings are corroborated by research examining the effects of structural lesions in the caudate and putamen on executive function (Monchi et al, 2006;Mesulam, 2000;Iversen, 1979).…”

Section: Discussionmentioning

confidence: 99%

Association of Amphetamine-Induced Striatal Dopamine Release and Cortisol Responses to Psychological Stress

Wand

Oswald

McCaul

et al. 2007

Neuropsychopharmacol

148

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Preclinical studies have shown that stress and glucocorticoids increase mesolimbic dopamine (DA) and thereby facilitate psychostimulant self-administration. The relationship between stress-induced cortisol and mesolimbic DA responses to psychostimulants has not been studied in humans. To test the hypotheses that glucocorticoid responses to psychological stress are correlated with DA and subjective responses to psychostimulants in humans, 25 healthy adults (18-29 years) completed the Trier Social Stress Test (TSST) and two positron emission tomography (PET) scans with high-specific [ 11 C]raclopride. The first scan was preceded by intravenous saline and the second by amphetamine (AMPH). Findings showed that stress-induced cortisol levels were positively associated with AMPH-induced DA release in the ventral striatum and other striatal regions. Subjects with higher cortisol responses to stress also reported more positive subjective drug effects with AMPH than subjects with lower responses. The results are consistent with preclinical findings showing an interrelationship between glucocorticoids and mesolimbic DA dynamics, which may influence psychostimulant self-administration in humans.

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“…Specifically, given the evidence for (1) clear aging-related decline in the striatal DA transporter (Erixon-Lindroth et al, 2005;Rinne et al, 1998;Troiano et al, 2010) as well as in D2 receptor binding (Bäckman et al, 2000;Kaasinen et al, 2000); and (2) their involvements in episodic memory (Cervenka et al, 2008;Erixon-Lindroth et al, 2005;Morcom et al, 2010;Takahashi et al, 2007), we focused on the effects of the DA transporter (DAT) gene and the D2 receptor gene on backward serial memory.…”

Section: Introductionmentioning

confidence: 99%

“…Given the role of DA in modulating frontalhippocampal memory processes (Cervenka et al, 2008;Erixon-Lindroth et al, 2005;Morcom et al, 2010;Takahashi et al, 2007), we expected these individuals to perform better in backward serial recall. Further, on the basis of the resourcemodulation hypothesis , these effects should be magnified in old age.…”

Section: Introductionmentioning

confidence: 99%

Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory

Papenberg

Nagel

et al. 2013

Neurobiology of Aging

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Aging compromises dopamine transporter (DAT) and receptor mechanisms in the frontostriatal circuitry. In a sample of 1288 younger and older adults, we investigated (i) whether individual differences in genotypes of the DAT gene (i.e., SLC6A3, the DAT variable number of tandem repeat 9/9, 9/10, and 10/10) and in the D2 receptor (DRD2) gene (i.e., the C957T [rs6277] CC and any T) interactively contribute to phenotype variations in episodic memory performance; and (ii) whether these genetic effects are magnified in older adults, because of considerable declines in the dopamine functions. Our results showed that carrying genotypes associated with higher levels of striatal synaptic dopamine (DAT 9/9) and higher density of extrastriatal D2 receptors (C957T CC) were associated with better backward serial recall, an episodic memory task with high encoding and retrieval demands. Critically, the gene-gene interaction effect was reliably stronger in older than in younger adults. In line with the resource modulation hypothesis, our findings suggest that aging-related decline in brain phenotypes (e.g., dopamine functions) could alter the relations between genotypes and behavioral phenotypes (e.g., episodic memory).

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The role of the striatal dopamine transporter in cognitive aging

Cited by 219 publications

References 72 publications

The correlative triad among aging, dopamine, and cognition: Current status and future prospects

The correlative triad among aging, dopamine, and cognition: Current status and future prospects

Association of Amphetamine-Induced Striatal Dopamine Release and Cortisol Responses to Psychological Stress

Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory

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