Frontiers in Aging Neuroscience

Correction: Distinguishing early from late mild cognitive impairment: a multi-level analysis of regional morphometry and KLS-derived network topology

2026-04-01

Peng Yan, Xinyu Du, Siyu Yang

Mitigating cognitive decline in Alzheimer's disease dementia by enhancing cognitive reserve through neuroplasticity in addition to amyloid-β reduction

2026-03-30

Takayoshi Ubuka, Kazuko Yuyama, Akito Genjima, Mika Nagakura, Keiko Kato, Sayuri Hayashi, Naofumi Makino, Takeshi Yamane, Takeshi Hirose, Yoichi Yamane

Exercise suppresses apoptosis for alleviating Parkinson’s disease: effects on pathophysiological molecular pathways

2026-03-27

Junfei Chen, Xin Liu, Yue Wu, Chunlong Wang, Cong Wang

Parkinson’s disease (PD) is characterized by the progressive degeneration of midbrain dopaminergic neurons, with apoptosis representing the predominant mechanism of neuronal cell death among the various forms of cell death implicated in PD. The lack of effective strategies to inhibit neuronal apoptosis remains a major challenge in PD management, particularly given the limitations associated with current pharmacological interventions. Exercise has gained increasing attention as a potentially effective approach to reduce PD symptoms and may alter disease progression by regulating apoptosis. However, the exact molecular pathways by which exercise provides neuroprotective benefits in PD remain incompletely understood. This narrative review synthesizes current evidence from animal models and human studies on the molecular mechanisms by which exercise alleviates neuronal apoptosis in PD. Following a comprehensive literature search of PubMed, Web of Science, and Scopus databases, we critically evaluate the evidence for exercise-mediated regulation of three key interconnected pathways: mitochondrial function (AMPK/Sirt1/PGC-1α signaling), neuroinflammation (TLR/MyD88/NF-κB signaling), and autophagy (CaMKII/Beclin1/p62 signaling). We discuss the translational limitations of current animal studies, identify gaps in the literature including the predominance of treadmill-based protocols and limited human evidence, and propose an integrative framework linking these pathways to coordinated neuroprotection. Understanding these molecular interactions will inform the development of optimized, personalized exercise interventions for PD management.

Age-group differences between young and middle-aged adults in spatiotemporal EEG dynamics revealed by instantaneous frequency microstate analysis

2026-03-26

Sou Nobukawa, Takashi Ikeda, Mitsuru Kikuchi, Tetsuya Takahashi

IntroductionThe human brain exhibits complex functions that emerge from interactions among spatially distributed neural regions. Electroencephalography (EEG) microstate analysis has been widely adopted to capture transient topographies reflecting large-scale network dynamics; moreover, it has been linked to cognitive functions, intrinsic brain networks, and neuropsychiatric disorders. Building on this framework, we recently proposed a novel approach based on instantaneous frequency (IF), defined as the temporal derivative of the instantaneous phase, which characterizes microstates in a dimension distinct from that of conventional amplitude-based microstates by explicitly capturing the phase leading and lagging. Although IF microstates have shown promise in characterizing the pathology and cognitive decline in Alzheimer's, their relevance to normal aging has not been investigated. This study aimed to identify age-group differences in large-scale EEG-dynamic properties using IF microstates.MethodsWe recorded resting-state EEG with eyes closed from 29 younger and 18 middle-aged healthy adults. IF time series were extracted from sensor-level EEG signals in the theta and alpha bands. The IF microstates were identified using a hidden Markov model to ensure temporal continuity in state segmentation. Subsequently, we evaluated the sensor-level spatial distributions, mean dwell times, occupancy, and transition probabilities of the IF microstates and assessed age-group differences using appropriate statistical tests with false discovery rate correction.ResultsWe identified several IF microstates characterized by frontal IF delay and occipital IF lead, as well as microstates deviating from these patterns. Group comparisons revealed age-group differences in dynamic properties; in the middle-aged group, mean dwell times increased in some states and decreased in others, while occupancy and transition probabilities also exhibited significant changes.DiscussionIF microstate analysis provides a novel and informative perspective on age-group differences in spatiotemporal EEG dynamics. This approach, which is distinct from conventional amplitude-based microstates, may be useful for understanding healthy aging neural mechanisms.