Frontiers in Aging Neuroscience最新文献

Objectives: The study aims to investigate the predictive performance of preoperative imaging features combined with tap test for the outcomes of ventriculoperitoneal (VP) shunt in idiopathic normal pressure hydrocephalus (iNPH).

Methods: In this multicenter retrospective study, 166 iNPH patients who underwent VP shunt surgery between August 2019 and November 2023 were included. Preoperative clinical characteristics and imaging features were collected. Preoperative clinical assessment and at least 3 months of postoperative follow-up were performed. Multivariable logistic regression, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were used to evaluate predictive performance.

Results: Out of 166 total patients, 96 were responders and 70 non-responders. The tap test showed significant difference between two group (p < 0.01). Multivariable logistic regression identified that a positive disproportionately enlarged subarachnoid space (DESH) sign (OR = 0.09, 95% CI: 0.04-0.22, p < 0.001) and a sharper callosal angle (CA) (OR = 0.97, 95% CI: 0.95-1.00, p = 0.02) were associated with symptom improvement after shunt. The sensitivity, specificity, and AUC of tap test were 0.64, 0.60, and 0.62, respectively. Combining CA and the tap test increased sensitivity to 0.85, while combining DESH, CA, and the tap test improved specificity and AUC to 0.67 and 0.72, respectively.

Conclusion: The findings suggest that the imaging features DESH and CA, when combined with the tap test, enhance the prediction of VP shunt outcomes in iNPH patients. Despite the improved predictive capability, further research focusing on innovative biomarkers for VP shunt is warranted.

Objective: Gait disorder represents a characteristic symptom of Parkinson's disease (PD), and exercise has been established as an effective intervention for gait management in PD. However, the relative efficacy of various exercise types in improving gait among PD patients remains unclear. This study aimed to compare the effectiveness of different movement-based interventions in enhancing gait for individuals with PD through a network meta-analysis.

Methods: A comprehensive search was conducted across multiple databases, including PubMed, Cochrane Library, Embase, Web of Science, and CNKI. The methodological quality of included studies was evaluated using the Cochrane Bias risk tool. Data was extracted from these studies to compare the efficacy of 29 distinct exercise interventions on gait performance in patients with PD.

Results: The analysis encompassed 68 randomized controlled trials (RCTs), involving a total of 3,114 participants. The results of the network meta-analysis showed that DE is higher than CON (SMD, 2.11; 95% CI 1.07 to 3.15), WE (SMD, 2.16; 95% CI 0.90 to 3.43), HE (SMD, 2.19; 95% CI 0.95 to 3.44), OE (SMD, 2.66; 95% CI 1.16 to 4.16), TR (SMD, 2.62; 95% CI 1.45 to 3.79) to better improve Gait velocity in patients with Parkinson's disease. DE is superior to CON (SMD, 2.08; 95% CI 0.04 to 4.13) in improving Step length. FAE is superior to CON (SMD, 1.01; 95% CI 0.04 to 1.98), BDJ (SMD, 1.20; 95% CI 0.15 to 2.25), RAGT (SMD, 1.29; 95% CI 0.07 to 2.52), DE (SMD, 1.57; 95% CI 0.36 to 2.77), TR (SMD, 1.62; 95% CI 0.48 to 2.76), OE (1.76, 95% CI 0.57 to 2.94) in improving Gait velocity. RAGT is superior to CT (MD, 2.02; 95% CI 0.41 to 3.63), TR (MD, 2.51; 95% CI 1.17 to 3.84), AE (MD, 2.66; 95% CI 0.45 to 4.88), BDJ (MD, 2.77; 95% CI 0.93 to 4.61), CON (MD, 2.83; 95% CI 1.30 to 4.36), DTT (MD, 12.84; 95% CI 10.05 to 15.63) in improving 6MWT.

Conclusion: Our study found that DE improved gait speed and step length in patients with Parkinson's disease better than other forms of exercise. FAE and RAGT were more effective than other exercises in improving step length and 6MWT in patients with Parkinson's disease.

Background: The exact mechanisms of PD are unclear, but Parkin-mediated mitophagy dysfunction is believed to play a key role. We investigated whether blood levels of Parkin and other biomarkers are linked to the risk of developing PD.

Methods: Baseline blood measures of Parkin and other biomarkers, including Homocysteine, carcinoembryonic antigen, Urea, total proteins, total cholesterol, creatine kinase, and albumin, were collected from 197 clinically diagnosed Parkinson's disease participants and 107 age-matched healthy controls in Wenzhou Parkinson's Biomarkers and Living Characteristics study. We conducted bioinformatics analysis using three datasets from the GEO database: GSE90514 (Cohort 1: PD = 4, HC = 4), GSE7621 (Cohort 2: PD = 16, HC = 9), and GSE205450 (Cohort 3: PD = 69, HC = 81).

Results: Using a bioinformatic approach, we identified dysregulated biological processes in PD patients with PRKN mutations. Compared to controls, significant abnormalities were observed in blood levels of Parkin, Hcy, total proteins, urea, albumin, and CEA in PD patients. A model incorporating Parkin, Hcy, total proteins, and urea effectively distinguished PD from healthy controls, achieving a higher accuracy (AUC 0.841) than other biomarker combinations. Gene set enrichment analysis suggested that pathways such as PINK1-Parkin-mediated mitophagy, urea cycle, cysteine degradation, and riboflavin metabolism may be involved in PRKN mutation. Additionally, the link between Parkin and PD was partially mediated by CEA and albumin, not by Hcy, total proteins, or urea.

Conclusion: Our findings indicate that blood Parkin levels may be a minimally invasive biomarker for PD diagnosis. The model, which included Parkin, Hcy, total proteins, and urea, effectively distinguished PD from HC with greater accuracy.

Background: The atherogenic index of plasma (AIP) has been proposed as a novel biomarker predictor for dyslipidemia and has been linked to various diseases. In this study, we explored the relationship between AIP levels and cognitive impairment in a middle-aged and older population.

Methods: This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS) for 7,918 individuals aged 45 and older. The AIP was calculated as the logarithmic ratio of triglycerides to high-density lipoprotein cholesterol. To assess the relationship between the AIP and cognitive impairment, logistic regression models were employed, while restricted cubic spline analysis was conducted to explore potential non-linear associations between AIP levels and cognitive impairment.

Results: The study participants had a mean age of 58.4 ± 8.8 years, and 49.1% were female. From 2011 to 2018, 2,911 participants (36.8%) developed cognitive impairment. After adjusting for potential confounders, the AIP was found to be significantly associated with cognitive impairment. In particular, participants in the higher AIP quartiles (Q2: odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.24-1.69, P < 0.001, Q3: OR: 1.63, 95% CI: 1.40-1.91, P < 0.001, and Q4: OR: 1.68, 95% CI: 1.43-1.98, P < 0.001) showed an increased risk of cognitive impairment compared to those in the lowest quartile (Q1). Additionally, a non-linear relationship was observed between AIP levels and cognitive impairment risk (P for nonlinear < 0.001).

Conclusion: The study finds that elevated AIP levels are linked to an increased risk of cognitive impairment in middle-aged and older adults, suggesting that managing dyslipidemia could help reduce this risk.

Background: Cognitive decline is a chronic condition which is characterized by a loss of the ability to remember, learn, and pay attention to complex tasks. Many older people are now suffering from cognitive decline, which decreases life quality and leads to disability. This study aimed to identify the risk and protective factors for cognitive decline of the older people from daily life and establish a predictive model using logistic regression.

Methods: We investigated 3,790 older people with health examination and questionnaires which included information associated with physical condition, lifestyle factors, and cognitive status. Single-factor comparison, principal component analysis with a Manova-Wilk test, multiple linear regression, and logistic regression were performed to filter the risk and protective factors regarding cognitive decline of older individuals. Then a predictive model using logistic regression was established based on the most significant protective and risk factors.

Results: We found a significant separation along the coordinate axis between people with normal and declined cognition by principal component analysis, as confirmed by the Manover-Wilk test. Single-factor comparison, multiple linear regression and logistic regression implied that gender, age, hypertension level, height, dietary habit, physical-exercise duration, physical-exercise history, and smoking history could be closely linked with cognitive decline. We also observed significant differences in height, physical exercise duration, physical-exercise years, and smoking years between the male and female of the participants. ROCs of the predictive model by logistic regression were plotted, with AUC values of 0.683 and 0.682, respectively, for the training and testing sets. Although an effective predictive model is thought to have AUC over 0.7, we still believe that the present model is acceptable because the value is close to the threshold.

Conclusion: The protective factors of cognitive decline for older people were male gender, height, keeping moderate exercising, and nicotine stimulation, and the risk factors included age, female gender, vegetarianism and hypertension. Except for the genetic factor, differences in lifestyle, such as smoking and exercise habits, may contribute to the observed differences in cognitive function between genders. The significant results could be utilized in the practice for the early intervention of cognitive decline in aged people.

Background: The aging population in China is confronted with considerable challenges, with 14.71% of elderly individuals affected by mild cognitive impairment (MCI). The practice of Tai Chi has been demonstrated to enhance cognitive function, while sensory stimulation has been shown to facilitate neural activity. Nevertheless, the combined impact of Tai Chi and sensory stimulation on cognitive, sensory functions, and brain activation in older adults with MCI remains uncertain. This study aims to ascertain whether the integration of Tai Chi with sensory stimulation can facilitate more efficacious interventions for these outcomes.

Methods and analysis: The TaiChi-MSS (Tai Chi and Multisensory Stimulation for Cognitive Function) study is a multi-center, randomized controlled trial (RCT) conducted in Suzhou and Shanghai, enrolling 88 participants aged 60 years or older with MCI. Participants will be randomly assigned to one of four groups: Tai Chi, multisensory stimulation, Tai Chi combined with multisensory stimulation or control. The intervention will last 6 months, with follow-up assessments at 3, 6, and 9 months. Primary outcomes include cognitive and sensory assessments, assessed using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), domain-specific cognitive tests, Pure Tone Audiometry (PTA), and Sniffin' Sticks Odor Identification Test. Secondary outcomes involve brain activation, measured through functional Magnetic Resonance Imaging (fMRI) scans. fMRI will be used to assess brain structure and connectivity changes, focusing on neuroplasticity. Data will be analyzed using mixed-effects models. The False Discovery Rate (FDR) will be the correction method for multiple comparisons to control for the expected proportion of false positives.

Ethics and dissemination: This study was approved by the ethics committee of Shanghai University of Sport (No. 102772023RT200). The results of this study will be disseminated in peer-reviewed journals and presented at academic conferences.

Alzheimer's disease (AD) is a severe neurodegenerative disease characterized mainly by the formation of amyloid beta (Aβ) plaques and abnormal phosphorylation of tau. In recent years, an imbalance in iron homeostasis has been recognized to play a key role in the pathological process of AD. Abnormal iron accumulation can activate various kinases such as glycogen synthase kinase-3β, cyclin-dependent kinase 5, and mitogen-activated protein kinase, leading to abnormal phosphorylation of tau and amyloid precursor protein, and accelerating the formation of Aβ plaques and neurofibrillary tangles. In addition, iron-mediated oxidative stress not only triggers neuronal damage, but also exacerbates neuronal dysfunction by altering the phosphorylation of N-methyl-D-aspartate receptors and γ-aminobutyric acid type A receptors. Iron accumulation also affects the phosphorylation status of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, interfering with the dopamine signaling pathway. On the other hand, iron affects iron transport and metabolism in the brain by regulating the phosphorylation of transferrin, further disrupting iron homeostasis. Therapeutic strategies targeting iron metabolism show promise by reducing iron accumulation, inhibiting oxidative stress, and reducing abnormal phosphorylation of key proteins. This article reviews the molecular mechanisms of phosphorylation modifications mediated by iron homeostasis imbalance in AD, and discusses the potential of interventions that regulate iron metabolism and related signaling pathways, providing a new theoretical basis for the treatment of AD.

Background: Urinary dysfunction is an early manifestation of autonomic dysfunction in Multiple System Atrophy (MSA) and often precedes orthostatic hypotension. This study investigated the diagnostic efficacy of post-void residual (PVR) urine volume in differentiating possible MSA from early-stage Parkinson's disease (PD) and sought to identify a feasible combination of autonomic nervous system indicators for clinical use. The distribution of α-Synuclein (α-Syn) forms in erythrocyte was preliminary explored.

Methods: This study included 70 patients with MSA-P, 73 with MSA-C, and 71 with PD. All participants underwent assessments including bladder residual urine ultrasound, the supine-to-standing test (STS), external anal sphincter electromyography (EAS-EMG), brain MRI, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Receiver operating characteristic (ROC) curves determined the diagnostic value of PVR urine volume and other autonomic indicators for possible MSA. Immunofluorescence staining of α-Syn forms in red blood cells (RBCs) was also performed.

Results: PVR urine volume, ΔSBP and ΔDBP (at 1 and 3 min), and EAS-EMG parameters were significantly increased in MSA-P and MSA-C patients compared to PD (p < 0.01), with similar differences observed between possible MSA-P/MSA-C and early-stage PD patients. ROC analysis showed that PVR urine volume had diagnostic value in differentiating possible MSA-P (AUC = 0.668, cut-off 24.5 mL) and MSA-C (AUC = 0.759, cut-off 47.5 mL) form early-stage PD patients. ΔSBP at 1 and 3 min also distinguished possible MSA-P (AUC = 0.702, 0.730) and MSA-C (AUC = 0.707, 0.718) from early-stage PD. Combining PVR urine volume and ΔSBP (at 1 and 3 min) further improved diagnostic accuracy, with an AUC of 0.817 (sensitivity 57.1%, specificity 96.8%) for possible MSA-P and an AUC of 0.794 (sensitivity 68.6%, specificity 87.1%) for MSA-C from early-stage PD. On a molecular level, oligo-α-Syn predominantly localized to RBC membrane fractions in MSA patients, while α-Syn pS129 was primarily detected in the RBC cytoplasm of PD patients.

Conclusion: Combining PVR urine volume and ΔSBP (at 1 and 3 min) is an easily accessible and effective method for distinguishing possible MSA from early-stage PD. This combination should be considered for routine assessment in Parkinsonism. Distinct α-Syn forms distribution in erythrocytes could be considered as a useful biomarker for differential diagnosis.

Background: Mild cognitive impairment (MCI) is associated with an increased risk of dementia in older adults. Olfactory impairment may indicate prodromal dementia, yet its underlying mechanisms are not fully understood. This study aimed to investigate the alterations in functional connectivity (FC) of odor-induced olfactory neural circuits in MCI patients.

Methods: The study included 39 MCI patients and 42 normal controls (NCs). All subjects underwent cognitive assessments, olfactory behavior tests, and odor-based functional magnetic resonance imaging (fMRI). Differences in FC within olfactory circuits were analyzed using the generalized psychophysiological interaction (gPPI) method.

Results: Mild cognitive impairment patients showed significant cognitive deficits, including lower scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), alongside impairments in episodic memory, visuospatial memory, executive function, language, attention, olfactory threshold, and total olfactory function. Compared to NCs, MCI patients exhibited reduced activation in the bilateral primary olfactory cortex (bPOC) during olfactory stimulation. Odor-induced bPOC activation correlated with olfactory thresholds across the cohort. During odor stimulation, MCI patients showed increased FC from the bPOC to the right anterior frontal lobe, particularly the middle frontal gyrus (MFG) and superior frontal gyrus (SFG). Conversely, FC from the right anterior frontal lobe to the medial temporal cortex, including the fusiform and parahippocampal gyri, was reduced in MCI patients. Increased FC from the bPOC to the right SFG/MFG negatively correlated with episodic memory, while decreased FC to the right fusiform/parahippocampal gyri positively correlated with attention, language ability, and olfactory identification.

Conclusion: This study indicates that impaired FC within the primary olfactory cortex (POC)-anterior frontal cortex-medial temporal cortex circuit is a sensitive neuroimaging marker for early MCI identification. The primary dysfunction appears in the POC, suggesting that FC alterations from this region may provide novel diagnostic and therapeutic avenues for early intervention.

Although the phenomena underlying cognitive decline and dementia are complex, there is growing evidence suggesting that degraded sensory inputs caused by age-related hearing loss may play a central role in accelerating cognitive decline in older individuals. Further supporting this notion is evidence that hearing augmentation with hearing aids can mitigate hearing loss-related cognitive impairments. Despite this evidence, few studies have attempted to investigate hearing aid efficacy with a focus on cognitive outcome measures. In this preliminary study, we sought to determine if certain demographic and audiological factors are linked to individual differences regarding observed cognitive changes following hearing aid use. We show that several factors can explain large portions of the variance observed in cognitive score changes following short-term hearing aid use in first-time users, suggesting that it might be possible to develop predictive algorithms to determine individualized estimates of the cognitive benefit of hearing aid use. Future studies with larger sample sizes are warranted, in particular, to explore a wider array of cognitive functions, investigate a greater range of potential predictors, and better quantify their relative contribution to outcome measure estimates.