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Failure to modulate attentional control in advanced aging linked to white matter pathology.

ABSTRACT: Advanced aging is associated with reduced attentional control and less flexible information processing. Here, the origins of these cognitive effects were explored using a functional magnetic resonance imaging task that systematically varied demands to shift attention and inhibit irrelevant information across task blocks. Prefrontal and parietal regions previously implicated in attentional control were recruited by the task and most so for the most demanding task configurations. A subset of older individuals did not modulate activity in frontal and parietal regions in response to changing task requirements. Older adults who did not dynamically modulate activity underperformed their peers and scored more poorly on neuropsychological measures of executive function and speed of processing. Examining 2 markers of preclinical pathology in older adults revealed that white matter hyperintensities (WMHs), but not high amyloid burden, were associated with failure to modulate activity in response to changing task demands. In contrast, high amyloid burden was associated with alterations in default network activity. These results suggest failure to modulate frontal and parietal activity reflects a disruptive process in advanced aging associated with specific neuropathologic processes.

SUBMITTER: Hedden T

PROVIDER: S-EPMC3328340 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Failure to modulate attentional control in advanced aging linked to white matter pathology.

Hedden Trey T Van Dijk Koene R A KR Shire Emily H EH Sperling Reisa A RA Johnson Keith A KA Buckner Randy L RL

Cerebral cortex (New York, N.Y. : 1991) 20110717 5

Advanced aging is associated with reduced attentional control and less flexible information processing. Here, the origins of these cognitive effects were explored using a functional magnetic resonance imaging task that systematically varied demands to shift attention and inhibit irrelevant information across task blocks. Prefrontal and parietal regions previously implicated in attentional control were recruited by the task and most so for the most demanding task configurations. A subset of older ...[more]

PMID: 21765181

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Project description:ImportanceProgressive parkinsonism is common in older adults without a diagnosis of Parkinson disease and is associated with adverse health outcomes, but its pathologic basis is controversial.ObjectiveTo examine if the burden of cerebral white matter hyperintensity (WMH), a common manifestation of cerebrovascular disease pathologies, is associated with the rate of progressive parkinsonism.Design, setting, and participantsThis community-based cohort study included participants recruited in 3 ongoing cohorts that began enrollment in 1994, 1997, and 2004. Prior to death, participants were observed for a mean of 7.5 years, with annual clinical assessments. From 4427 participants enrolled in the 3 cohorts, 2134 died. Postmortem autopsy was performed in 1725 decedents, and 598 also had ex vivo brain magnetic resonance imaging. Participants were excluded if they were missing any of the 9 postmortem pathology indices (n = 22) or repeated parkinsonism assessment (n = 41) or had received a clinical diagnosis of Parkinson disease at any point before or during the study (n = 19). Data were analyzed from April 2020 to August 2021.ExposuresWMH burden was assessed using a modified Fazekas rating scale.Main outcomes and measuresParkinsonism was assessed annually using 26 items of a modified motor portion of the Unified Parkinson's Disease Rating Scale. A summary score was developed from the item scores, with higher scores indicating more severe parkinsonism.ResultsOf 516 included decedents, 364 (70.5%) were female, and the mean (SD) age at death was 90.2 (6.4) years. Higher WMH was associated with faster progressive parkinsonism (estimate, 0.024; SE, 0.008; P = .002). The attenuation of this association was greater when controlling for indices of cerebrovascular disease pathologies than when controlling for neurodegenerative pathologies (cerebrovascular disease: estimate, 0.019; SE, 0.008; P = .02; neurodegenerative: estimate, 0.022; SE, 0.008; P = .003), but both remained significant.Conclusions and relevanceIn this cohort study, higher levels of both WMH and indices of cerebrovascular disease pathologies in aging brains were associated with more rapid progressive parkinsonism. Further studies are needed to determine if in vivo brain imaging of older adults for evidence of WMH and aggressive medical treatment of vascular risk factors and diseases can reduce the occurrence or severity of late-life parkinsonism.

Dataset Information

Failure to modulate attentional control in advanced aging linked to white matter pathology.

Publications

Failure to modulate attentional control in advanced aging linked to white matter pathology.

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