Unlocking the enigma: unraveling multiple cognitive dysfunction linked to glymphatic impairment in early Alzheimer’s disease

BackgroundAlzheimer’s disease (AD) is one of the world’s well-known neurodegenerative diseases, which is related to the balance mechanism of production and clearance of two proteins (amyloid-β and tau) regulated by the glymphatic system. Latest studies have found that AD patients exhibit impairments to their glymphatic system. However, the alterations in the AD disease continuum, especially in the early stages, remain unclear. Moreover, the relationship between the glymphatic system and cognitive dysfunction is still worth exploring.MethodsA novel diffusion tensor image analysis method was applied to evaluate the activity of the glymphatic system by an index for diffusivity along the perivascular space (ALPS-index). Based on this method, the activity of the glymphatic system was noninvasively evaluated in 300 subjects, including 111 normal controls (NC), 120 subjects with mild cognitive impairment (MCI), and 69 subjects with AD. Partial correlation analysis was applied to explore the association between glymphatic system and cognitive impairment based on three domain-general scales and several domain-specific cognitive scales. Receiver operating characteristic curve analysis was used to evaluate the classification performance of ALPS-index along the AD continuum.ResultsALPS-index was significantly different among NC, MCI and AD groups, and ALPS-index decreased with cognitive decline. In addition, ALPS-index was significantly correlated with the scores of the clinical scales (p<0.05, FDR corrected), especially in left hemisphere. Furthermore, combination of ALPS and fractional anisotropy (FA) values achieved better classification results (NC vs. MCI: AUC = 0.6610, NC vs. AD: AUC = 0.8214).ConclusionHere, we show that the glymphatic system is closely associated with multiple cognitive dysfunctions, and ALPS-index can be used as a biomarker for alterations along the AD continuum. This may provide new targets and strategies for the treatment of AD, and has the potential to assist clinical diagnosis

Berberine Ameliorates High Glucose-Induced Cardiomyocyte Injury via AMPK Signaling Activation to Stimulate Mitochondrial Biogenesis and Restore Autophagic Flux

Background: Type II diabetes (T2D)-induced cardiomyocyte hypertrophy is closely linked to the impairment of mitochondrial function. Berberine has been shown to be a promising effect for hypoglycemia in T2D models. High glucose-induced cardiomyocyte hypertrophy in vitro has been reported. The present study investigated the protective effect and the underlying mechanism of berberine on high glucose-induced H9C2 cell line.Methods: High glucose-induced H9C2 cell line was used to mimic the hyperglycemia resulting in cardiomyocyte hypertrophy. Berberine was used to rescue in this model and explore the mechanism in it. Confocal microscopy, immunofluorescence, RT-PCR, and western blot analysis were performed to evaluate the protective effects of berberine in high glucose-induced H9C2 cell line.Results: Berberine dramatically alleviated hypertrophy of H9C2 cell line and significantly ameliorated mitochondrial function by rectifying the imbalance of fusion and fission in mitochondrial dynamics. Furthermore, berberine further promoted mitogenesis and cleared the damaged mitochondria via mitophagy. In addition, berberine also restored autophagic flux in high glucose-induced cardiomyocyte injury via AMPK signaling pathway activation.Conclusion: Berberine ameliorates high glucose-induced cardiomyocyte injury via AMPK signaling pathway activation to stimulate mitochondrial biogenesis and restore autophagicflux in H9C2 cell line

Integration of Consonant and Pitch Processing as Revealed by the Absence of Additivity in Mismatch Negativity

Consonants, unlike vowels, are thought to be speech specific and therefore no interactions would be expected between consonants and pitch, a basic element for musical tones. The present study used an electrophysiological approach to investigate whether, contrary to this view, there is integrative processing of consonants and pitch by measuring additivity of changes in the mismatch negativity (MMN) of evoked potentials. The MMN is elicited by discriminable variations occurring in a sequence of repetitive, homogeneous sounds. In the experiment, event-related potentials (ERPs) were recorded while participants heard frequently sung consonant-vowel syllables and rare stimuli deviating in either consonant identity only, pitch only, or in both dimensions. Every type of deviation elicited a reliable MMN. As expected, the two single-deviant MMNs had similar amplitudes, but that of the double-deviant MMN was also not significantly different from them. This absence of additivity in the double-deviant MMN suggests that consonant and pitch variations are processed, at least at a pre-attentive level, in an integrated rather than independent way. Domain-specificity of consonants may depend on higher-level processes in the hierarchy of speech perception

Multimodal Functional Network Connectivity: An EEG-fMRI Fusion in Network Space

EEG and fMRI recordings measure the functional activity of multiple coherent networks distributed in the cerebral cortex. Identifying network interaction from the complementary neuroelectric and hemodynamic signals may help to explain the complex relationships between different brain regions. In this paper, multimodal functional network connectivity (mFNC) is proposed for the fusion of EEG and fMRI in network space. First, functional networks (FNs) are extracted using spatial independent component analysis (ICA) in each modality separately. Then the interactions among FNs in each modality are explored by Granger causality analysis (GCA). Finally, fMRI FNs are matched to EEG FNs in the spatial domain using network-based source imaging (NESOI). Investigations of both synthetic and real data demonstrate that mFNC has the potential to reveal the underlying neural networks of each modality separately and in their combination. With mFNC, comprehensive relationships among FNs might be unveiled for the deep exploration of neural activities and metabolic responses in a specific task or neurological state