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Dopamine and frontostriatal networks in cognitive aging.

ABSTRACT: Recent studies have linked dopamine to differences in behavior and brain activity in normal individuals. We explored these relationships in older and younger adults by investigating how functional connectivity between the striatum and prefrontal cortex is related to caudate dopamine and verbal working memory task performance. We studied 12 young and 18 older participants with functional magnetic resonance imaging (fMRI) during this task, and used positron emission tomography with the tracer 6-[(18)F]-fluoro-L-m-tyrosine (FMT) to assess dopamine synthesis capacity. Younger adults had a greater extent of frontal caudate functional connectivity during the load-dependent delay period of the working memory task than the older participants. Across all subjects, the extent of this functional connectivity was negatively correlated with dopamine synthesis capacity, such that participants with the greatest connectivity had the lowest caudate 6-[(18)F]-fluoro-L-m-tyrosine (FMT) signal. Additionally, the extent of functional connectivity was positively correlated with working memory performance. Overall these data suggest interdependencies exist between frontostriatal functional connectivity, dopamine, and working memory performance and that this system is functioning suboptimally in normal aging.

SUBMITTER: Klostermann EC

PROVIDER: S-EPMC3245323 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Dopamine and frontostriatal networks in cognitive aging.

Klostermann Ellen C EC Braskie Meredith N MN Landau Susan M SM O'Neil James P JP Jagust William J WJ

Neurobiology of aging 20110420 3

Recent studies have linked dopamine to differences in behavior and brain activity in normal individuals. We explored these relationships in older and younger adults by investigating how functional connectivity between the striatum and prefrontal cortex is related to caudate dopamine and verbal working memory task performance. We studied 12 young and 18 older participants with functional magnetic resonance imaging (fMRI) during this task, and used positron emission tomography with the tracer 6-[( ...[more]

PMID: 21511369

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Project description:BACKGROUND:Across networks, connectivity within the frontoparietal network (FPN) and cingulo-opercular network (CON) exhibits reductions earliest during healthy aging, contributing to cognitive impairment. Individuals with psychotic disorders demonstrate evidence of accelerated aging across multiple biological systems. By leveraging a large sample of patients with psychosis from early to chronic illness stages, this study sought to determine whether the CON and FPN exhibit evidence of accelerated aging in psychotic disorders, confirm associations between network efficiency and cognition, and determine whether reduced network efficiency is observed in early-stage psychosis. METHODS:Resting-state functional magnetic resonance imaging and cognitive data were obtained on 240 patients with psychotic disorder and 178 healthy control participants (HCs). Global efficiency, a measure of functional integration, was calculated for the CON, FPN, subcortical network, and visual network. Associations with age and cognition were assessed and compared between groups. RESULTS:Consistent with accelerated aging, significant group by age interactions reflected significantly stronger relationships between efficiency and age in patients with psychosis than in HCs for both the CON (psychosis: r = -.37; HC: r = -.16) and FPN (psychosis: r = -.31; HC: r = -.05). Accelerated aging was not observed in either the subcortical or visual network, suggesting specificity for cognitive networks that decline earliest in healthy aging. Replicating prior findings, efficiency of both the CON and FPN correlated with cognitive function across all participants (rs > .11, ps < .031). Furthermore, patients with chronic psychosis (p = .004), but not patients with early psychosis (p = .553), exhibited significantly lower FPN efficiency compared with HCs. CONCLUSIONS:Functional integration of higher-order cognitive networks is intact in early psychosis but exhibits evidence of accelerated aging, suggesting the potential for intervention targeting cognition within the early psychosis period.

Project description:In accordance with the physiological networks that underlie it, human cognition is characterized by both the segregation and interdependence of a number of cognitive domains. Cognition itself, therefore, can be conceptualized as a network of functions. A network approach to cognition has previously revealed topological differences in cognitive profiles between healthy and disease populations. The present study, therefore, used graph theory to determine variation in cognitive profiles across healthy aging and cognitive impairment. A comprehensive neuropsychological test battery was administered to 415 participants. This included three groups of healthy adults aged 18-39 (n = 75), 40-64 (n = 75), and 65 and over (n = 70) and three patient groups with either amnestic (n = 75) or non-amnestic (n = 60) mild cognitive impairment or Alzheimer's type dementia (n = 60). For each group, cognitive networks were created reflective of test-to-test covariance, in which nodes represented cognitive tests and edges reflected statistical inter-nodal significance (p < 0.05). Network metrics were derived using the Brain Connectivity Toolbox. Network-wide clustering, local efficiency and global efficiency of nodes showed linear differences across the stages of aging, being significantly higher among older adults when compared with younger groups. Among patients, these metrics were significantly higher again when compared with healthy older controls. Conversely, average betweenness centralities were highest in middle-aged participants and lower among older adults and patients. In particular, compared with controls, patients demonstrated a distinct lack of centrality in the domains of semantic processing and abstract reasoning. Network composition in the amnestic mild cognitive impairment group was similar to the network of Alzheimer's dementia patients. Using graph theoretical methods, this study demonstrates that the composition of cognitive networks may be measurably altered by the aging process and differentially impacted by pathological cognitive impairment. Network alterations characteristic of Alzheimer's disease in particular may occur early and be distinct from alterations associated with differing types of cognitive impairment. A shift in centrality between domains may be particularly relevant in identifying cognitive profiles indicative of underlying disease. Such techniques may contribute to the future development of more sophisticated diagnostic tools for neurodegenerative disease.

Dataset Information

Dopamine and frontostriatal networks in cognitive aging.

Publications

Dopamine and frontostriatal networks in cognitive aging.

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