Explore the vast range of titles available.

Background Increasing evidence suggests an association between pro-inflammatory diets and cognitive function. However, only a few studies based on small sample sizes have explored the association between pro-inflammatory diets and dementia using the dietary inflammatory index (DII). Additionally, the relationship between DII and different subtypes of dementia, such as Alzheimer's dementia and vascular dementia, remains largely unexplored. Given the changes in brain structure already observed in patients with dementia, we also investigated the association between DII and magnetic resonance imaging (MRI) measures of brain structure to provide some hints to elucidate the potential mechanisms between pro-inflammatory diet and cognitive decline. Methods A total of 166,377 UK Biobank participants without dementia at baseline were analyzed. DII calculations were based on the information collected by the 24-h recall questionnaire. Brain structural anatomy and tissue-specific volumes were measured using brain MRI. Cox proportional hazards models, competing risk models, and restricted cubic spline were applied to assess the longitudinal associations. The generalized linear model was used to assess the association between DII and MRI measurements. Results During a median follow-up time of 9.46 years, a total of 1372 participants developed dementia. The incidence of all-cause dementia increased by 4.6% for each additional unit of DII [hazard ratio (HR): 1.046]. Besides, DII displayed a “J-shaped” non-linear association with Alzheimer’s dementia ( P nonlinear  = 0.003). When DII was above 1.30, an increase in DII was significantly associated with an increased risk of Alzheimer’s dementia (HR: 1.391, 95%CI: 1.085–1.784, P  = 0.009). For brain MRI, the total volume of white matter hyperintensities increased with an increase in DII, whereas the volume of gray matter in the hippocampus decreased. Conclusions In this cohort study, higher DII was associated with a higher risk of all-cause dementia and Alzheimer’s dementia. However, our findings suggested that the association with DII and vascular and frontotemporal dementia was not significant.

Background Nuclear acetyl-CoA pools govern histone acetylation that controls synaptic plasticity and contributes to cognitive deterioration in patients with Alzheimer’s disease (AD). Nuclear acetyl-CoA pools are generated partially from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). However, the underlying mechanism of histone acetylation dysregulation in AD remains poorly understood. Methods We detected ACSS2 expression and histone acetylation levels in the brains of AD patients and 5 × FAD mice. When we altered ACSS2 expression by injecting adeno-associated virus into the dorsal hippocampus of 5 × FAD mice and replenished ACSS2 substrate (acetate), we observed changes in cognitive function by Morris water maze. We next performed RNA-seq, ChIP-qPCR, and electrophysiology to study molecular mechanism underlying ACSS2-mediated spatial learning and memory in 5 × FAD mice. Results We reported that ACSS2 expression and histone acetylation (H3K9, H4K12) were reduced in the hippocampus and prefrontal cortex of 5 × FAD mice. Reduced ACSS2 levels were also observed in the temporal cortex of AD patients. 5 × FAD mice exhibited a low enrichment of acetylated histones on the promoters of NMDARs and AMPARs, together with impaired basal and activity-dependent synaptic plasticity, all of which were rescued by ACSS2 upregulation. Moreover, acetate replenishment enhanced ac-H3K9 and ac-H4K12 in 5 × FAD mice, leading to an increase of NMDARs and AMPARs and a restoration of synaptic plasticity and cognitive function in an ACSS2-dependent manner. Conclusion ACSS2 is a key molecular switch of cognitive impairment and that targeting ACSS2 or acetate administration may serve as a novel therapeutic strategy for the treatment of intermediate or advanced AD. Graphical Abstract Nuclear acetyl-CoA pools are generated partly from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). Model depicts that ACSS2 expression is downregulated in the brains of 5×FAD model mice and AD patients. Of note, ACSS2 downregulation mediates a reduction in ionotropic glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD. These deficits can be rescued by ACSS2 upregulation or acetate supplementation (GTA, an FDA-approved food additive), which may serve as a promising therapeutic strategy for AD treatment.

Population-based studies reveal that apolipoprotein E (APOE) ε4 gene allele is closely associated with late-life depression (LLD). However, its exact role and underlying mechanism remain obscure. The current study found that aged apoE4-targeted replacement (TR) mice displayed obvious depression-like behavior when compared with age-matched apoE3-TR mice. Furthermore, apoE4 increased stress-induced depression-like behaviors, accompanied by declines in the hippocampal 5-HT (1A) radioligand [18F] MPPF uptake evidenced by positron emission tomography (PET). In [18F]-fluorodeoxyglucose PET ([18F]-FDG PET) analyses, the FDG uptake in the prefrontal cortex, temporal cortex and hippocampus of apoE4-TR mice significantly declined when compared with that of apoE3-TR mice after acute stress. Further biochemical analysis revealed that ATP levels in the prefrontal cortex of apoE4-TR mice decreased during aging or stress process and ATP supplementation effectively rescued the depression-like behaviors of elderly apoE4-TR mice. In primary cultured astrocytes from the cortex of apoE-TR mice, apoE4, when compared with apoE3, obviously decreased the mitochondrial membrane potential, mitochondrial respiration, and glycolysis in a culture time-dependent manner. Our findings highlight that apoE4 is a potential risk factor of depression in elderly population by impairing the glucose metabolism, reducing ATP level, and damaging mitochondrial functions in astrocytes, which indicates that in clinical settings ATP supplementation may be effective for elderly depression patients with apoE4 carrier.

Small molecule RNAs (microRNAs) are a kind of endogenous, stable, and noncoding RNA molecule that can regulate the expression of target genes such as DJ-1 at the posttranscriptional level. This study aimed to detect the expression of salivary microRNAs and to discover their value as a salivary potential biomarker for Parkinson's disease (PD). Through a case-control study, RT-qPCR technology was used to detect the expression of miR-874 and miR-145-3p in the saliva of 30 PD patients and 30 healthy volunteers. Then we compared the differences in the expression levels of salivary miR-874 and miR-145-3p between the PD group and the control group and analyzed the correlation between the expression of salivary miR-874 and miR-145-3p in terms of age, gender, disease condition, and disease course. We found that salivary miR-874 and miR-145-3p were both positively expressed in the PD group and control group, and their expression in the PD group was higher than that in the control group. The expression of salivary miRNA-874 and miR-145-3p had no clear correlation to age, gender, total RNA concentrations in saliva, the score of UPDRSII, UPDRSIII, olfactory test scale, MMSE, MoCA, Hohn-Yahr stage and disease course. In conclusion, in the PD group and the control group with positive expression, the expression levels of miR-874 and miR-145-3p in the PD group were higher than those in the control group. The detection of miR-874 and miR-145-3p expression in saliva can be used as an auxiliary biomarker for PD.

Parkinson’s disease (PD) is a common dyskinesia disease, the mitochondrial unfolded protein response (mtUPR) may be directly or indirectly involved in the occurrence and development of PD, although the exact mechanism is unclear. We established a dopaminergic neuronal-like cell model of PD, by overexpression of PGC-1α to detect evaluate the expression of proteases and molecular chaperones of involved in the mtUPR, as well as the expression of PGC-1α and LRPPRC, illustrated the distribution of LRPPRC. Remarkably, the mtUPR activation reached maximal at 24 h after MPP + treatment in SH-SY5Y cells, which the protein and transcription levels of the proteases and molecular chaperones reached maximal. The proteases and molecular chaperones were significantly increased when overexpressed PGC-1α, which indicated that PGC-1α overexpression activated the mtUPR, and PGC-1α had a protective effect on SH-SY5Y cells. The expression levels of PGC-1α and LRPPRC were significantly improved in the PGC-1α overexpression groups. LRPPRC was markedly reduced in the nucleus, suggesting that PGC-1α overexpression may play a protective role to the mitochondria through LRPPRC. Our finding indicates that overexpression of PGC-1α may activate mtUPR, reducing the oxidative stress injury induced by MPP + through LRPPRC signaling, thus maintain mitochondrial homeostasis.

Background Nonmotor symptoms (NMSs) are under-recognized in progressive supranuclear palsy (PSP), despite their considerable impact on quality of life. The full spectrum and impact of NMSs in PSP remain insufficiently understood. This study is aimed to investigate NMSs in patients with PSP and compare the difference of NMSs between patients with PSP and patients with Parkinson’s disease (PD). Methods The study involved 44 patients diagnosed with PSP and 132 patients with PD. NMSs were assessed using a range of evaluation tools. Additionally, the relationship between NMSs and disease severity, as well as the impact on quality of life was analyzed. Results The Non-Motor Symptom Scale (NMSS) and Movement Disorders Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I scores were significantly higher in patients with PSP than in patients with PD (42.52 ± 25.64 vs. 32.06 ± 21.45, p  = 0.007; 11.89 ± 6.24 vs. 9.80 ± 5.61, p  = 0.049). The severity of urinary symptoms was also greater in patients with PSP than in those with PD. Although clinically suspected rapid eye movement sleep behavior disorder (RBD), which was not assessed using polysomnography but rather through RBD Screening Questionnaire, was less common in patients with PSP compared with those with PD, cognitive impairment was more frequent and severe in patients with PSP. Hyposmia, cardiovascular symptoms, constipation, sleep disturbances, emotional symptoms, fatigue, and pain exhibited similar severity and frequency in both patient groups. Only emotional symptoms in patients with PSP were associated with the 39-item Parkinson’s Disease Questionnaire scores, and none of the NMSs were associated with Hoehn & Yahr stage or MDS-UPDRS Part III scores. Conclusion PSP is characterized by a higher burden of NMSs than PD, with some different and common symptom profiles. The impact of emotional symptoms on the quality of life in PSP underscores the importance of addressing these symptoms in clinical care to improve patient outcomes.

Background Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. NOX2, a cytochrome subunit of NOX, transports electrons across the plasma membrane to generate ROS, leading to physiological and pathological processes. Heme oxygenase-1 (HO-1) can be rapidly induced by oxidative stress and other noxious stimuli in the brain or other tissues. Astaxanthin (ATX), a carotenoid with antioxidant properties, is 100–1000 times more effective than vitamin E. The present study investigated the neuroprotective effects of ATX on MPP + -induced oxidative stress in PC12 cells. Results MPP + significantly decreased MTT levels in a concentration-dependent manner. Hemin, SnPPIX and ATX didn’t exhibit any cytotoxic effects on PC12 cells. Pretreatment with ATX (5, 10, 20 μM), caused intracellular ROS production in the MPP + group to decrease by 13.06%, 22.13%, and 27.86%, respectively. MPP + increased NOX2, NRF2 and HO-1 protein expression compared with control (p < 0.05). Co-treatment with hemin or ATX suppressed NOX2 expression (p < 0.01), and greatly increased NRF2 and HO-1 expression (p < 0.01). MPP + treatment up-regulated both NOX2 (p < 0.01) and HO-1 (p < 0.01) mRNA levels. Co-treatment with hemin or ATX significantly increased HO-1 mRNA levels (p < 0.01), and decreased NOX2 mRNA levels (p < 0.01). MPP + increased NOX2 and HO-1 expression with considerable fluorescence extending out from the perinuclear region toward the periphery; this was attenuated by DPI. Co-treatment with hemin or ATX significantly up-regulated HO-1 expression and decreased NOX2 expression with considerable fluorescence intensity (stronger than the control and MPP + groups). Conclusions ATX suppresses MPP + -induced oxidative stress in PC12 cells via the HO-1/NOX2 axis. ATX should be strongly considered as a potential neuroprotectant and adjuvant therapy for patients with Parkinson’s disease.

Abstract Background: In recent years, increasing attention has been paid to cryptogenic stroke (CS) caused by the patent foramen ovale (PFO). Objective: This study aims to evaluate the value of microbubble transcranial Doppler (MB-TCD) combined with contrast transthoracic echocardiography (cTTE) in the diagnosis of cryptogenic stroke patients with PFO. Materials and Method: From January 2014 to January 2019, patients who suffered from CS were recruited and divided into the cTTE group and MB-TCD combined with cTTE group. All patients were further checked by transesophageal echocardiography (TEE). Results: A total of 130 patients accepted cTTE examination, and 109 patients accepted MB-TCD combined with cTTE. In the group, 52 of the 54 positive patients were finally confirmed by TEE with PFO, and 12 of the 76 negative patients were finally confirmed by TEE with PFO. In combined group, 50 patients were negative on both two examination (Negative group), 54 were positive on both two examination (Positive group) and finally confirmed by TEE indeed with patent foramen ovale (PFO), while remaining five (5) patients were positive only on MB-TCD (Suspected group). After checked by TEE, three (3) of five patients with MB-TCD positive were confirmed by TEE indeed with PFO. The sensitivity, specificity, positive likelihood ratio (+LR), and Youden's index of cTEE in diagnostic of cryptogenic stroke patients with PFO were 81.25%, 96.97%, 26.82 and 0.78, respectively, and these for MB-TCD combined with cTTE were 100%, 96.15%, 25.97 and 0.96, respectively. MB-TCD medium can sensitively discover PFO in cryptogenic stroke patients with 100% sensitivity and a missdiagnosis rate of 0. Conclusion: The combination of MB-TCD and cTTE can improve the sensitivity and specificity of PFO diagnosis in cryptogenic stroke patients. MB-TCD medium also had high sensitivity and specificity.

This study aimed to investigate the role of cerebellar magnetic resonance imaging (MRI) features in identifying mild cognitive impairment (MCI). This retrospective multicenter study included patients with MCI, patients with Alzheimer's disease (AD), and healthy controls (HCs) from three tertiary hospitals in China (January 2022-December 2023). Cerebellar and hippocampal radiomics features were extracted from T1-, T2-, and T2-FLAIR-weighted MRI. A sparse representation classifier was developed using 10-fold cross-validation and was validated on independent datasets. Diagnostic performance was assessed through sensitivity, specificity, and ROC-AUC values. A total of 87 patients with MCI, 109 patients with AD, and 55 healthy controls (HCs) matched by gender and age were included for model construction and validation. Additionally, 13 patients with MCI and 26 patients with AD were included for external validation. The 10-fold cross-validation accuracy and ROC AUC for identifying cognitive impairment (CI) in the training set using a combination of cerebellar T1, T2, and T2-FLAIR weighted images were better than those of hippocampal models (91.0% vs. 86.8%, 0.943 vs. 0.931). The accuracy and ROC AUC in the independent test set were similar (89.3% vs. 89.3%, 0.908 vs. 0.906). The 10-fold cross-validation accuracy and ROC AUC for identifying MCI in the training set, using a combination of cerebellar T1, T2, and T2-FLAIR weighted images, were similar to those of hippocampal models (85.2% vs. 83.7%, 0.877 vs. 0.905). Furthermore, the results were consistent with the external validation set (89.7% vs. 93.1%, 0.962 vs. 0.974). Cerebellar MRI radiomics models exhibit diagnostic accuracy comparable to hippocampal models for identifying CI and MCI, supporting the cerebellum's role in detecting early cognitive dysfunction. These findings provide novel insights into cerebellar contributions to AD pathophysiology and offer potential biomarkers for clinical application.