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Summary: As people age, the brain networks associated with cognition become less efficient at information transfer and more vulnerable to disturbance.
Source: Duke-NUS Medical School
Functional regions within the brain become less distinct and inter-connected in the elderly over time, especially in those networks related to attention span and cognition. The finding, published by researchers at Duke-NUS Medical School in the Journal of Neuroscience, adds to the current understanding of longitudinal decline in brain network integrity associated with aging.
“We currently live in a rapidly aging society,” said the study’s corresponding author, Associate Professor Juan Helen Zhou, a neuroscientist from the faculty of Duke-NUS’ Neuroscience and Behavioural Disorders program. “Compared to cross-sectional studies, it is vital to understand brain changes over time that underlie both healthy and pathologic aging, in order to inform efforts to slow down cognitive aging.”
The human brain contains functionally segregated neuronal networks with dense internal connections and sparse inter-connectivity. Aging is thought to be associated with reduced functional specialization and segregation of these brain networks.
Joint senior authors Assoc Prof Zhou and Prof Michael Chee, Director of Duke-NUS’ Centre for Cognitive Neuroscience, led the research team, collecting data from neuropsychological assessments and functional magnetic resonance imaging (fMRI) brain scans from a cohort of 57 healthy young adults and 72 healthy elderly Singaporeans. Each elderly participant was scanned two to three times during a period of up to four years. The neuropsychological assessments tested participants’ ability to process information quickly, focus their attention, remember verbal and visuospatial information, and plan and execute tasks. The fMRI scans measured how brain regions are functionally connected based on low-frequency blood oxygenation level fluctuations over time. Participants were asked to relax with their eyes open and remain still as these were performed.
Dr. Joanna Chong, first author of the paper and a Ph.D. graduate from Assoc Prof Zhou’s lab at Duke-NUS, developed approaches to convert the fMRI images into graphic representations that depict the inter- and intra-network connectedness of each individual’s brain. She then compared differences in brain functional networks between the young and elderly participants, and in the elderly over time.
The team tracked changes in brain functional networks that affected specific cognitive abilities, such as goal-oriented thought and action, and choosing where to focus attention. As one ages, these networks associated with cognition are less efficient in information transfer, more vulnerable to disturbance, and less distinctive.
“Overall, our research advances understanding of brain network changes over time, underlying cognitive decline in healthy aging,” said Assoc Prof Zhou.
“This can facilitate future work to identify elderly individuals at risk of aging-related disorders or to identify strategies that can preserve cognitive function.”
Commenting on the study, Prof Patrick Casey, Senior Vice Dean for Research at Duke-NUS, stated, “Ageing is a significant risk factor for a variety of chronic diseases in people, including neurodegenerative and cerebrovascular diseases. Governments worldwide are concerned about the public health implications of increasingly aging populations. Basic research such as this plays a vital role in informing efforts to help us stay healthy longer as we live longer lives.”
The researchers aim to next examine how various factors, such as genetic and cardiovascular risks, might influence aging-related changes in brain networks. By studying a larger group of healthy young, middle-aged and older adults, they hope to develop better ways to predict cognitive decline.
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Source: Duke-NUS Medical School Media Contacts: Federico Graciano – Duke-NUS Medical School Image Source: The image is in the public domain.
Original Research: Closed access “Longitudinal Changes in the Cerebral Cortex Functional Organization of Healthy Elderly”. Joanna Su Xian Chong, Kwun Kei Ng, Jesisca Tandi, Chenhao Wang, Jia-Hou Poh, June C. Lo, Michael W.L. Chee and Juan Helen Zhou. Journal of Neuroscience. doi:10.1523/JNEUROSCI.1451-18.2019
Longitudinal Changes in the Cerebral Cortex Functional Organization of Healthy Elderly
Healthy aging is accompanied by disruptions in the functional modular organization of the human brain. Cross-sectional studies have shown age-related reductions in the functional segregation and distinctiveness of brain networks. However, less is known about the longitudinal changes in brain functional modular organization and their associations with aging-related cognitive decline. We examined age- and aging-related changes in functional architecture of the cerebral cortex using a dataset comprising a cross-sectional healthy young cohort of 57 individuals (mean ± SD age, 23.71 ± 3.61 years, 22 males) and a longitudinal healthy elderly cohort of 72 individuals (mean ± baseline age, 68.22 ± 5.80 years, 39 males) with 2–3 time points (18–24 months apart) of task-free fMRI data. We found both cross-sectional (elderly vs young) and longitudinal (in elderly) global decreases in network segregation (decreased local efficiency), integration (decreased global efficiency), and module distinctiveness (increased participation coefficient and decreased system segregation). At the modular level, whereas cross-sectional analyses revealed higher participation coefficient across all modules in the elderly compared with young participants, longitudinal analyses revealed focal longitudinal participation coefficient increases in three higher-order cognitive modules: control network, default mode network, and salience/ventral attention network. Cross-sectionally, elderly participants also showed worse attention performance with lower local efficiency and higher mean participation coefficient, and worse global cognitive performance with higher participation coefficient in the dorsal attention/control network. These findings suggest that healthy aging is associated with whole-brain connectome-wide changes in the functional modular organization of the brain, accompanied by loss of functional segregation, particularly in higher-order cognitive networks.
SIGNIFICANCE STATEMENT Cross-sectional studies have demonstrated age-related reductions in the functional segregation and distinctiveness of brain networks. However, longitudinal aging-related changes in brain functional modular architecture and their links to cognitive decline remain relatively understudied. Using graph theoretical and community detection approaches to study task-free functional network changes in a cross-sectional young and longitudinal healthy elderly cohort, we showed that aging was associated with global declines in network segregation, integration, and module distinctiveness, and specific declines in distinctiveness of higher-order cognitive networks. Further, such functional network deterioration was associated with poorer cognitive performance cross-sectionally. Our findings suggest that healthy aging is associated with system-level changes in brain functional modular organization, accompanied by functional segregation loss particularly in higher-order networks specialized for cognition.
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