The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate from their typical trajectories. MRI-derived brain age (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or that lack neuroanatomic interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training on the MRIs of 4,681 cognitively normal (CN) participants and testing on 1,170 CN participants from an independent sample. BA estimation errors are notably lower than those of previous studies. At both individual and cohort levels, the CNN provides detailed anatomic maps of brain aging patterns that reveal sex dimorphisms and neurocognitive trajectories in adults with mild cognitive impairment (MCI, N = 351) and Alzheimer’s disease (AD, N = 359). In individuals with MCI (54% of whom were diagnosed with dementia within 10.9 y from MRI acquisition), BA is significantly better than CA in capturing dementia symptom severity, functional disability, and executive function. Profiles of sex dimorphism and lateralization in brain aging also map onto patterns of neuroanatomic change that reflect cognitive decline. Significant associations between BA and neurocognitive measures suggest that the proposed framework can map, systematically, the relationship between aging-related neuroanatomy changes in CN individuals and in participants with MCI or AD. Early identification of such neuroanatomy changes can help to screen individuals according to their AD risk.
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Diet modulates brain network stability, a biomarker for brain aging, in young adults
Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale ( n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester ( d -β-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degeneration occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.
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- NSF-PAR ID:
- 10186963
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 117
- Issue:
- 11
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- 6170 to 6177
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Background Cognitive training may partially reverse cognitive deficits in people with HIV (PWH). Previous functional MRI (fMRI) studies demonstrate that working memory training (WMT) alters brain activity during working memory tasks, but its effects on resting brain network organization remain unknown.
Purpose To test whether WMT affects PWH brain functional connectivity in resting‐state fMRI (rsfMRI).
Study Type Prospective.
Population A total of 53 PWH (ages 50.7 ± 1.5 years, two women) and 53
HIV ‐seronegative controls (SN , ages 49.5 ± 1.6 years, six women).Field Strength/Sequence Axial single‐shot gradient‐echo echo‐planar imaging at 3.0 T was performed at baseline (TL1), at 1‐month (TL2), and at 6‐months (TL3), after WMT.
Assessment All participants had rsfMRI and clinical assessments (including neuropsychological tests) at TL1 before randomization to Cogmed WMT (adaptive training,
n = 58: 28 PWH, 30 SN; nonadaptive training,n = 48: 25 PWH, 23 SN), 25 sessions over 5–8 weeks. All assessments were repeated at TL2 and at TL3. The functional connectivity estimated by independent component analysis (ICA) or graph theory (GT) metrics (eigenvector centrality, etc.) for different link densities (LDs) were compared between PWH and SN groups at TL1 and TL2.Statistical Tests Two‐way analyses of variance (ANOVA) on GT metrics and two‐sample
t ‐tests on FC or GT metrics were performed. Cognitive (eg memory) measures were correlated with eigenvector centrality (eCent) using Pearson's correlations. The significance level was set atP < 0.05 after false discovery rate correction.Results The ventral default mode network (vDMN) eCent differed between PWH and SN groups at TL1 but not at TL2 (
P = 0.28). In PWH, vDMN eCent changes significantly correlated with changes in the memory ability in PWH (r = −0.62 at LD = 50%) and vDMN eCent before training significantly correlated with memory performance changes (r = 0.53 at LD = 50%).Data Conclusion ICA and GT analyses showed that adaptive WMT normalized graph properties of the vDMN in PWH.
Evidence Level 1
Technical Efficacy 1
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Abstract Cognitive decline is amongst one of the most commonly reported complaints during normal aging. Despite evidence that age and cognition are linked with similar neural correlates, no previous studies have directly ascertained how these two constructs overlap in the brain in terms of neuroimaging‐based prediction. Based on a long lifespan healthy cohort (CamCAN, aged 19–89 years,
n = 567), it is shown that both cognitive function (domains spanning executive function, emotion processing, motor function, and memory) and human age can be reliably predicted from unique patterns of functional connectivity, with models generalizable in two external datasets (n = 533 andn = 453). Results show that cognitive decline and normal aging both manifest decrease within‐network connections (especially default mode and ventral attention networks) and increase between‐network connections (somatomotor network). Whereas dorsal attention network is an exception, which is highly predictive on cognitive ability but is weakly correlated with aging. Further, the positively weighted connections in predicting fluid intelligence significantly mediate its association with age. Together, these findings offer insights into why normal aging is often associated with cognitive decline in terms of brain network organization, indicating a process of neural dedifferentiation and compensational theory. -
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Abstract Human brains experience whole-brain anatomic and functional changes throughout the lifespan. Age-related whole-brain network changes have been studied with functional magnetic resonance imaging (fMRI) to determine their low-frequency spatial and temporal characteristics. However, little is known about age-related changes in whole-brain fast dynamics at the scale of neuronal events. The present study investigated age-related whole-brain dynamics in resting-state electroencephalography (EEG) signals from 73 healthy participants from 6 to 65 years old via characterizing transient neuronal coactivations at a resolution of tens of milliseconds. These uncovered transient patterns suggest fluctuating brain states at different energy levels of global activations. Our results indicate that with increasing age, shorter lifetimes and more occurrences were observed in the brain states that show the global high activations and more consecutive visits to the global highest-activation brain state. There were also reduced transitional steps during consecutive visits to the global lowest-activation brain state. These age-related effects suggest reduced stability and increased fluctuations when visiting high-energy brain states and with a bias toward staying low-energy brain states. These age-related whole-brain dynamics changes are further supported by changes observed in classic alpha and beta power, suggesting its promising applications in examining the effect of normal healthy brain aging, brain development, and brain disease.
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1073/pnas.1913042117
