RESUMEN
Tai Chi (TC) practice has been shown to improve both cognitive and physical function in older adults. However, the neural mechanisms underlying the benefits of TC remain unclear. Our primary aims are to explore whether distinct age-related and TC-practice-related relationships can be identified with respect to either temporal or spatial (within/between-network connectivity) differences. This cross-sectional study examined recurrent neural network dynamics, employing an adaptive, data-driven thresholding approach to source-localized resting-state EEG data in order to identify meaningful connections across time-varying graphs, using both temporal and spatial features derived from a hidden Markov model (HMM). Mann-Whitney U tests assessed between-group differences in temporal and spatial features by age and TC practice using either healthy younger adult controls (YACs, n = 15), healthy older adult controls (OACs, n = 15), or Tai Chi older adult practitioners (TCOAs, n = 15). Our results showed that aging is associated with decreased within-network and between-network functional connectivity (FC) across most brain networks. Conversely, TC practice appears to mitigate these age-related declines, showing increased FC within and between networks in older adults who practice TC compared to non-practicing older adults. These findings suggest that TC practice may abate age-related declines in neural network efficiency and stability, highlighting its potential as a non-pharmacological intervention for promoting healthy brain aging. This study furthers the triple-network model, showing that a balancing and reorientation of attention might be engaged not only through higher-order and top-down mechanisms (i.e., FPN/DAN) but also via the coupling of bottom-up, sensory-motor (i.e., SMN/VIN) networks.
RESUMEN
Vascular cognitive impairment and dementia (VaD) is the second most common type of dementia caused by chronic vascular hypoperfusion. Adiponectin, one of the cytokines produced by adipocytes (adipocytokine), plays a role in CNS pathologies, but its specific function in VaD is unknown. Here, transcriptomic analyses on human brain tissues showed downregulation of adipocytokine/PPAR signaling in VaD patients, with prominent upregulation of pro-inflammatory responses. Using the murine asymmetric common carotid artery stenosis (ACAS) model, we discovered that the adiponectin/PPARγ axis is essential in reducing chronic hypoperfusion-induced cognitive deficits via modulation of microglial function. Adiponectin levels in the plasma increased early after VaD induction, but decreased in the cerebrospinal fluid in the late phase of VaD. Adiponectin deficiency worsened hippocampus-dependent cognitive deficits, exacerbated neuroinflammation and microglia/macrophage activation, and amplified neuronal loss, but these behavioral and histological outcomes were rescued by adipoRon, a small molecule agonist of the adiponectin receptors. AdipoRon boosted PPARγ expression and inhibited pro-inflammatory microglial responses in vitro, thereby protecting ischemic neurons in primary microglia-neuron cocultures. Microglia/macrophage-specific knockout of PPARγ abolished the neuroprotective effects of adipoRon. Collectively, these data confirm the importance of adiponectin/PPARγ signaling in maintaining cognitive functions in chronic hypoperfusion-induced dementia, and thus provide novel therapeutic targets for VaD.