Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues

doi:10.1016/j.neubiorev.2009.12.008

Neuroscience & Biobehavioral Reviews

Volume 34, Issue 5, April 2010, Pages 670-677

https://doi.org/10.1016/j.neubiorev.2009.12.008 Get rights and content

Abstract

Molecular-imaging studies of dopaminergic neurotransmission measure biomarkers of dopamine (DA), such as the DA transporter and D₁ and D₂ receptor densities in the living brain. These studies indicate that individual differences in DA functions are linked to cognitive performance irrespective of age, and serve as powerful mediators of age-related decline in executive functioning, episodic memory, and perceptual speed. This focused review targets several recent findings pertaining to these relationships. Specifically, we discuss novel evidence concerning (a) the role of DA in within-person cognitive variability; (b) age-related differences in DA release during cognitive processing; (c) DA release following cognitive training in younger and older adults; and (d) the relationship between DA and task-induced functional brain activity. Based on these lines of empirical inquiry, we outline a series of avenues for future research on aging, DA, and cognition.

Section snippets

DA and within-person cognitive variability

Empirical evidence indicates that increased within-person performance fluctuations reflect suboptimal neuronal information processing (see MacDonald et al., 2006, for review), in line with propositions derived from computational models (e.g., Servan-Schreiber et al., 1990, Li et al., 2001). Higher levels of within-person behavioral variability in sensorimotor, perceptual, and cognitive tasks are often accompanied by lower mean levels of performance associated with various conditions (see Table 1

Age-related differences in DA release during cognitive processing

Cognitive performance in molecular-imaging studies is typically assessed outside the scanner; thus, the biomarker (e.g., receptor densities) is related to off-line cognitive markers (see Bäckman et al., 2006, Cropley et al., 2006, for reviews). There is, however, emerging evidence for in vivo mapping of actual release of DA, as assessed during cognitive activity. A paradigm used to address this issue involves contrasting DA binding in two conditions varying in cognitive load. DA release is

DA release following cognitive training in younger and older adults

Until relatively recently, adult cognitive intervention research was largely focused on training of strategies to boost episodic memory performance (for reviews, see Hill et al., 2000, Verhaeghen and Marcoen, 1996). A common assumption was that “hardware-based” cognitive functions such as working memory are less amenable to training and practice.

In recent years, however, several studies have demonstrated that extended practice may enhance performance in executively demanding situations such as

The relationship between DA and task-induced functional brain activity

For some time, we have argued for the importance of linking DA activity, blood flow, and behavior, thereby elucidating the chain that progresses from neuromodulation through functional activation to cognitive performance (e.g., Nyberg and Bäckman, 2004). The approach outlined in the preceding subsection on training, striatal BOLD response, and DA binding constitutes one step in that direction.

However, a direct way of addressing this issue is to collect PET-derived DA data and fMRI data on the

Concluding comments

We have reviewed new evidence on aging, DA, and cognition dealing with distinct, albeit interrelated, phenomena. These include the role of DA in processing fluctuations; age-related differences in DA release in response to cognitive activity and training; and the relationship between DA and the BOLD signal during cognitive activity. The novel findings emanating from these research themes solidify the assertion that DA is implicated in cognitive aging as well as in cognitive functioning

Acknowledgments

Preparation of this article was supported by grants from the Swedish Research Council and Swedish Brain Power to Lars Bäckman, who was also supported by an Alexander von Humboldt Research Award. Lars Nyberg was supported by grants from the Swedish Research Council and the Joint Committee for Nordic Research Councils in the Humanities and the Social Sciences. Ulman Lindenberger and Shu-Chen Li were supported by the Max Planck Society as well as the German Federal Ministry of Research and

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ReviewLinking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues

Abstract

Section snippets

DA and within-person cognitive variability

Age-related differences in DA release during cognitive processing

DA release following cognitive training in younger and older adults

The relationship between DA and task-induced functional brain activity

Concluding comments

Acknowledgments

Neurosci. Biobehav. Rev.

Neuroimage

Neurobiol. Aging

Neuroimage

Biol. Psychiatry

Psychiatr. Res. Neuroimag.

Neurosci. Biobehav. Rev.

Neurobiol. Aging

Neuroimage

Acta Psychol.

Trends Cognit. Sci.

Neurosci. Biobehav. Rev.

Neurocomputing

Neuropsychologia

Neuropsychologia

Trends Neurosci.

Brain Res.

Neurosci. Lett.

Cognit. Psychol.

Neuroimage

Neuroimage

Neuroimage

Neuroimage

Brain Res.

Neuroimage

Neurobiol. Aging

Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a PET study using high-affinity dopamine D2 receptor ligand [11C] FLB 457

J. Neurosci.

Prefrontal dopamine D1 receptors and working memory in schizophrenia

J. Neurosci.

Parallel organization of functionally segregated circuits linking basal ganglia and cortex

Annu. Rev. Neurosci.

Sensorimotor and forced expiratory volume as correlates of speed, accuracy, and variability in reaction time performance in late adulthood

Aging Neuropsychol. Cognit.

Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and [11C] raclopride

Arch. Neurol.

The role of dopamine functions in cognitive aging

Age-related cognitive deficits mediated by changes in the striatal dopamine system

Am. J. Psychiatry

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

Neurobiol. Aging

Cognitive deficits in Huntington's disease are predicted by dopaminergic PET markers and brain volumes

Brain

Aging and memory: cognitive and biological perspectives

Age-related and regional differences in dopamine mRNA expression in human midbrain

Neurology

Can training in a real-time strategy video game attenuate cognitive decline in older adults

Psychol. Aging

Memory plasticity across the life span: uncovering children's latent potential

Dev. Psychol.

Intraindividual variability as a marker of neurological dysfunction: a comparison of Alzheimer's disease and Parkinson's disease

J. Clin. Exp. Neuropsychol.

The multi-source interference task: validation study with fMRI in individual subjects

Mol. Psychiatry

Impact of working memory training on memory performance in old–old adults

Psychol. Aging

Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes

Nat. Rev. Neurosci.

Handbook of Aging and Cognition

Plasticity of executive functioning in young and old Adults: immediate training gains, transfer, and long-term maintenance

Psychol. Aging

Transfer of learning after updating training mediated by the striatum

Science

Remembering numbers in old age: mnemonic training versus self-generated strategy training

Aging Neuropsychol. Cognit.

The dopaminergic basis of human behaviors: AS review of molecular imaging studies

Neurosci. Biobehav. Rev.

Noise in the nervous system

Nat. Rev. Neurosci.

Mice lacking dopamine D2 and D3 receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention

Cereb. Cortex

Review
Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues

Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a PET study using high-affinity dopamine D₂ receptor ligand [¹¹C] FLB 457

Prefrontal dopamine D₁ receptors and working memory in schizophrenia

Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and [¹¹C] raclopride

Mice lacking dopamine D₂ and D₃ receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention