Frontiers in Aging Neuroscience最新文献

Background: Previous observational research has indicated a correlation between Parkinson's disease (PD) and multiple cancers; but the causality remains unclear. Thus, we utilized Mendelian randomization (MR) analysis to explore the potential causal link between PD and various cancers.

Methods: We conducted a bidirectional two-sample Mendelian randomization (TSMR) of genetic variants associated with PD and 14 types of cancers. Summary statistics on PD and 14 types of cancers were obtained from the International Parkinson's Disease Genomics Consortium and the study by Sakaue et al. The primary method employed was inverse variance weighted (IVW), complemented by multiple sensitivity analyses to evaluate heterogeneity and pleiotropy. The false discovery rate (FDR) was employed to control the false positive rate of multiple hypothesis testing.

Results: Following rigorous sensitivity analyses and corrections, our findings revealed suggestive associations between PD and certain cancers. We observed that PD decreases the risk of gastric cancer and colorectal cancer (OR = 0.936, 95% CI = 0.881-0.995, p = 0.034, P FDR = 0.239; OR = 0.955, 95% CI = 0.912-0.999, p = 0.046, P FDR = 0.215), while increasing the risk of breast cancer (OR = 1.043, 95% CI = 1.004-1.084, p = 0.029, P FDR = 0.402). Notably, we found no evidence supporting a reverse causal relationship. Additionally, in the reverse pathway, skin cancer demonstrated a suggestive causal relationship with PD (OR = 0.913, 95% CI = 0.857-0.973, p = 0.005, P FDR = 0.066).

Conclusion: Our MR analysis provides evidence supporting unidirectional suggestive causal relationships between PD and certain cancers. These findings enrich our comprehension of the intricate interplay between PD and cancer, warranting further investigation into the underlying biological mechanisms.

Introduction: This study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD).

Materials and methods: Utilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores.

Results: A significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered.

Discussion: The findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients.

Background: Mild cognitive impairment (MCI) is generally considered to have a high risk of progression to Alzheimer's disease. Our study aimed to investigate the abnormal functional connectivity (FC) in prefrontal cortex (PFC) in patients with MCI and explore the relationship between the observed changes and cognitive function.

Methods: Sixty-seven patients with MCI and 71 healthy individuals were recruited for this study. All participants underwent the Montreal Cognitive Assessment (MoCA) and functional near-infrared spectroscopy (fNIRS) examinations.

Results: Compared with healthy controls (HC), the patients with MCI exhibited significantly lower MoCA scores (p < 0.001). Through FC analysis, an enhanced subnetwork was observed in the right prefrontal cortex of the MCI group, covering four pairs of channel connections: CH12-CH15, CH12-CH16, CH13-CH15, and CH13-CH16. Moreover, the FC values of these four channel pairs and the education duration were significantly correlated with MoCA scores. Subsequently, a multiple linear regression model was performed to observe the independent factors of cognition decline, serving the education duration and the average FC values of subnetwork as independent variables and the MoCA scores as the dependent variable. The regression model showed a total of 25.7% explanation power (adjusted R² = 0.257, F = 24.723, p < 0.001).

Conclusion: Our study suggested that the enhanced subnetwork within the right PFC may be involved in the pathophysiology of MCI and serve as a potential target for the treatment of MCI.

[This corrects the article DOI: 10.3389/fnagi.2022.1077738.].

Introduction: Gait disturbances significantly impact the mobility and quality of life of individuals with Parkinson's disease (PD). This study aims to delve into the cortical mechanisms underlying gait disorders in PD, specifically focusing on the prefrontal cortex (PFC), premotor cortex (PMC), and primary somatosensory cortex (PSC).

Objective: To compare the functional connectivity of the PFC, PMC, and PSC regions during walking between individuals with PD and healthy controls.

Methods: The study included 30 individuals with PD (mean age 62.40 ± 7.16 years) and 22 healthy older adults (mean age 60.95 ± 6.34 years). All participants were requested to walk back and forth at a comfortable pace for 30 s over a 10-meter course three times. A mobile functional near-infrared spectroscopy (fNIRS) system was employed to evaluate the oxyhemoglobin concentration change (∆HbO2). To assess the interactions between the PFC, PMC, and PSC, the connectivity strength between different fNIRS channels was computed.

Results: Individuals with PD in the off-state exhibited significantly decreased walking speed and shorter stride length compared to the healthy controls. For six brain regions including the left (L) and right (R) PFC, PMC, and PSC, no significant differences in functional connectivity within each region were found between the PD and control groups. However, when it comes to the functional connectivity between every two regions, the PD group exhibited stronger functional connectivity than the control group in the LPFC-LPMC, LPFC-RPMC, LPFC-LPSC, RPFC-LPMC, RPFC-LPSC, LPMC-LPSC, LPMC-RPSC, and RPMC-RPSC. Positive correlations were found between gait performance (speed and stride length) and functional connectivity within the RPMC as well as between the RPMC and the RPSC.

Conclusion: Individuals with PD exhibit notable gait disturbances and increased functional connectivity in brain regions responsible for sensorimotor integration and motor function in their off-state. Strengthening the functional connectivity within the RPMC and between the RPMC and the RPSC could be a potential target for future treatments of gait impairments in PD.

Introduction: Depressive symptoms are most common non-motor symptoms in Parkinson's disease (PD), which is often overlooked due to absence of rapid and objective diagnostic biomarkers. Electroencephalography (EEG)-based event-related potentials (ERPs) is commonly used to assess emotional processes. The aim of this study was to investigate changes in ERPs in PD patients exhibiting depressive symptoms and to provide a reliable biomarker for assisting in the diagnosis of PD with depressive symptoms.

Methods: We conducted a case-control study involving 30 PD patients with (dPD group) or without depressive symptoms (nPD group) and 13 age matched healthy controls (HC). We recorded EEG of the patients during the emotional picture stimulation task and analyzed the difference in the early ERPs potentials (P1, N170, early posterior negativity) and their correlation with the severity of symptoms in PD patients.

Results: Our results found that P1 amplitude in the occipital region of the dPD group in response to emotional faces was significantly higher than that of nPD and HC group, and it was positively correlated with severity of depressive symptoms in PD patients.

Conclusion: Our study shows that facial expression-induced enhancement of P1 amplitude can be utilized as a rapid and objective indicator to screen for depressive symptoms in PD.

Purpose: This study aimed to investigate the characteristics of individuals with amyloid levels below the threshold. To achieve this, we differentiated between two groups: those with global amyloid negativity but focal deposition [G(-)F(+)] and those without focal deposition [G(-)F(-)].

Materials and methods: A total of 2,677 participants were diagnosed with cognitive unimpairment (CU) or mild cognitive impairment (MCI). MRI-based regional centiloid (CL) values were used to establish threshold values for each brain region. After applying a cutoff of 20 rdcCL to identify amyloid positivity, participants who were globally amyloid-negative were grouped into three categories: those who showed focal amyloid uptake [G(-)F(+)], individuals without focal amyloid deposition but with relatively high CL(HC) levels comparable to those in the focal uptake group [G(-)F(-) HC)], and those with relatively low CL(LC) levels [G(-)F(-) LC]. We compared the neuropsychological test results and brain structural changes between these groups using ANCOVA.

Results: The G(-)F(+) group demonstrated a lower cortical thickness (P < 0.001) than the G(-)F(-) HC group. In neuropsychological tests, the G(-)F(+) group exhibited lower the Seoul Verbal Learning Test delayed recall (SVLT-DR) and Mini Mental State Examination (MMSE), and showed progressed clinical status in the clinical dementia rating-sum of boxes (CDR-SOB) compared to the G(-)F(-) HC group (P < 0.001). The subsequent sensitivity analyses confirmed the persistence of these findings.

Conclusions: Individuals with focal amyloid deposition [G(-)F(+)] exhibited higher rates of cognitive impairment compared to patients with similar levels of amyloid, underscoring the importance of monitoring the progression of focal uptake, even when it remains below the amyloid threshold.

Objective: The diagnosis and treatment of biomarkers in Alzheimer's disease has emerged as a prominent topic within Alzheimer's disease research. In this paper, we conducted a bibliometric analysis of data from a wide range of literature in this field to enhance the in-depth understanding of this area.

Method: The core collection of the Science Citation Index database (web of science) was used to search for relevant literature in the above fields from 1 January 2006 to 14 November 2022 and Citespace software was used to visualize and analyze the literature data.

Results: A total of 1,138 papers were included, of which the United States ranked first with 607 papers and China ranked 6th in the world with 84 papers. The value of mediational centrality is 0.49 in the United States and 0.05 in China. In terms of the number of articles published by the research authors, the Swedish scholar Blennow Kaj ranks first with 82 articles published, and the scholars who rank second and third are Zetterberg Henrik (78 articles) and Morris John C (64 articles), respectively; in terms of the mediational centrality, the American scholar Trojanowski John Q ranked first in the world with 0.1, and the second and third ranked scholars were Blennow Kaj (0.09) and Zetterberg Henrik (0.06) respectively. Scholar JACK CR ranked first with 377 citation frequency. The journal NEUROLOGY is ranked first with 943 citations.

Conclusion: In recent years, global research in the field of biomarkers related to Alzheimer's disease has shown signs of softening, and the momentum of research has slightly diminished. However, this trend does not imply a decline in the quality of research. It is essential to enhance collaboration among countries, major research institutions, and scholars, with a particular emphasis on fostering international partnerships in the future.

Objective: Cerebrospinal fluid biomarkers are challenging to use for diagnosing mild cognitive impairment (MCI) in large populations, and there is an urgent need for new blood biomarkers. The aim of this study is to investigate whether astrocyte activation is correlated with hippocampal atrophy, and to assess the potential of glial fibrillary acidic protein (GFAP) as a biomarker for diagnosing MCI among community-dwelling older individuals.

Methods: This cross-sectional study included 107 older adults. The levels of GFAP in serum were measured, and the volumetric assessment of gray matter within hippocampal subregions was conducted using Voxel-Based Morphometry (VBM). The relationship between hippocampal subregion volume and blood biomarkers were analyzed using partial correlation. The effectiveness of blood biomarkers in differentiating MCI was assessed using a receiver operating characteristic (ROC) curve.

Results: We found that serum GFAP levels were significantly elevated in the MCI group compared to the cognitively normal (CN) group. Additionally, individuals with MCI exhibited a reduction gray matter volume in specific hippocampal subregions. Notably, the right dentate gyrus (DG) and right cornu ammonis (CA) subregions were found to be effective for distinguishing MCI patients from CN individuals. Serum levels of GFAP demonstrate a sensitivity of 65.9% and a specificity of 75.6% in differentiating patients with MCI from CN individuals.

Conclusion: Specific atrophy within hippocampal subregions has been observed in the brains of community-dwelling elderly individuals. Elevated levels of circulating GFAP may serve as a sensitive peripheral biomarker indicative of hippocampal-specific cognitive alterations in patients with MCI.