The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies As a Function of Age and Is Associated with Changes in Episodic Memory and Processing Speed
Adam M Staffaroni, Jesse A. Brown, K. Casaletto, F. Elahi, Jersey Deng, J. Neuhaus, Y. Cobigo, Paige S. Mumford, Samantha M. Walters, R. Saloner, A. Karydas, Gianluca Coppola, Howard J. Rosen, B. Miller, William W. Seeley, Joel H. Kramer
Journal of Neuroscience February 13, 2018 DOI: 10.1523/jneurosci.3067-17.2018 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Longitudinal Peer reviewed |
|---|---|
| Sample size | 111 |
| Population | Cognitively normal older human adults (ages 49–87) |
| Duration | Longitudinal (at least three task-free fMRI scans; 353 total scans) |
| Topics | Default mode network |
| Key findings | Default mode network and whole-brain functional connectivity follow a nonlinear trajectory with age, showing early increases and accelerating declines after age 74, and within-DMN connectivity changes are associated with episodic memory performance. |
Abstract
The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In this study, we evaluated longitudinal FC in 111 cognitively normal older human adults (ages 49–87, 46 women/65 men), 92 of whom had at least three task-free fMRI scans (n = 353 total scans). Whole-brain FC and three DMN subnetworks were assessed: (1) within-DMN, (2) between anterior and posterior DMN, and (3) between medial temporal lobe network and posterior DMN. Linear mixed-effects models demonstrated significant baseline age × time interactions, indicating a nonlinear trajectory. There was a trend toward increasing FC between ages 50–66 and significantly accelerating declines after age 74. A similar interaction was observed for whole-brain FC. APOE status did not predict baseline connectivity or change in connectivity. After adjusting for network volume, changes in within-DMN connectivity were specifically associated with changes in episodic memory and processing speed but not working memory or executive functions. The relationship with processing speed was attenuated after covarying for white matter hyperintensities (WMH) and whole-brain FC, whereas within-DMN connectivity remained associated with memory above and beyond WMH and whole-brain FC. Whole-brain and DMN FC exhibit a nonlinear trajectory, with more rapid declines in older age and possibly increases in connectivity early in the aging process. Within-DMN connectivity is a marker of episodic memory performance even among cognitively healthy older adults. SIGNIFICANCE STATEMENT Default mode network and whole-brain connectivity, measured using task-free fMRI, changed nonlinearly as a function of age, with some suggestion of early increases in connectivity. For the first time, longitudinal changes in DMN connectivity were shown to correlate with changes in episodic memory, whereas volume changes in relevant brain regions did not. This relationship was not accounted for by white matter hyperintensities or mean whole-brain connectivity. Functional connectivity may be an early biomarker of changes in aging but should be used with caution given its nonmonotonic nature, which could complicate interpretation. Future studies investigating longitudinal network changes should consider whole-brain changes in connectivity.
Comparable studies
Other observational and cohort studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A default mode of brain function Normal adult human brain | 2001 | Observational study | |
| Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network Healthy subjects | 2008 | Observational cohort | |
| Meditation experience is associated with increased cortical thickness Participants with extensive Insight meditation experience and matched controls | 2005 | Observational cohort | n = 20 |
| Meditation experience is associated with differences in default mode network activity and connectivity Experienced meditators and matched meditation-naive controls | 2011 | Observational cohort | |
| The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis Healthy subjects | 2008 | Observational study |
Citations in the library
Cited by 8
- Neuropsychological effect on long-term Ayahuasca use Counseling And Psychological Services Dissertations (Georgia State University) June 2, 2022
- Functional connectivity of default mode network in non-hospitalized patients with post-COVID cognitive complaints Frontiers in Neuroscience April 10, 2025
- Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation. Neuron December 1, 2023
- Age-related learning difficulty through trial-and-error method associated with decreased default mode network integration in healthy middle-aged adults. Journal of Clinical and Experimental Neuropsychology May 2023
- Longitudinal functional connectivity patterns of the default mode network in healthy older adults Neuroimage June 1, 2022
and 3 more in the library
Cites 2
- Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly Biological Psychiatry October 15, 2009
- Reduced functional segregation between the default mode network and the executive control network in healthy older adults: A longitudinal study Neuroimage March 19, 2016