Current Alzheimer research最新文献

Thioredoxin1 (Trx1) is a ubiquitous antioxidant protein that regulates the cell's redox status. Trx1's thiol redox activity protects neurons from various physiological processes that cause neuronal damage and neurodegeneration, including oxidative stress, apoptosis, and inflammation. Several studies have found that direct or indirect Trx1 regulation has neuroprotective effects in the brain, protecting against, preventing, or delaying neurodegenerative processes or brain traumas. This review focuses on the term neuroprotection, Trx1 localization, and expression in the brain, as well as its modulation concerning its neuroprotective effect in both animal and clinical models of ischemia, hypoxia, hemorrhage, traumatic brain injury, epilepsy, Alzheimer's disease, and Parkinson's disease.

Introduction: Sensory impairments (SIs, including visual, hearing, olfactory, and taste impairments) have been individually associated with age-related cognitive function. Little is known regarding their combined associations with cognitive function.

Methods: We included 2,931 participants (mean age of 69.1 years) from the National Health and Nutrition Examination Survey (NHANES, 2011-2014) and 10,785 participants (mean age of 70.2 years) from the National Health Interview Survey (NHIS, 2021). Status of visual, hearing, olfactory, and taste functions were self-reported in structured questionnaires. In NHANES, cognitive function was objectively measured by a battery of tests, including memory, verbal fluency, and processing speed. NHIS participants answered a single question about subjective cognitive complaints (SCC). We used regression models to assess the relation of the total number and the individual sensory impairments to z-scores of cognitive domains (linear regression) in NHANES and to SCC (logistic regression) in NHIS.

Results: A larger number of SI was related to poorer domain-specific cognitive function (all Ptrend <0.05), including memory (beta _{each additional SI} = -0.12, 95% confidence interval: -0.17 to -0.08), verbal fluency (-0.05, -0.10 to -0.01), and processing speed (-0.13, -0.16 to -0.09). In NHIS, each additional SI was related to 96% higher odds of SCC. We also observed independent associations of sensory impairments (except olfactory impairment) with specific cognitive domains. In addition, each individual SI was associated with higher odds of SCC (the odds ratios ranged from 1.30 to 1.78).

Conclusion: A larger number of SI was related to worse cognitive function and higher odds of SCC.

Background: Alterations in functional connectivity have been demonstrated in Alzheimer's disease (AD), an age-progressive neurodegenerative disorder that affects cognitive function; however, directional information flow has never been analyzed.

Objective: This study aimed to determine changes in resting-state directional functional connectivity measured using a novel approach, granger causality density (GCD), in patients with AD, and mild cognitive impairment (MCI) and explore novel neuroimaging biomarkers for cognitive decline detection.

Methods: In this study, structural MRI, resting-state functional magnetic resonance imaging, and neuropsychological data of 48 Alzheimer's Disease Neuroimaging Initiative participants were analyzed, comprising 16 patients with AD, 16 with MCI, and 16 normal controls. Volume-based morphometry (VBM) and GCD were used to calculate the voxel-based gray matter (GM) volumes and directed functional connectivity of the brain. We made full use of voxel-based between-group comparisons of VBM and GCD values to identify specific regions with significant alterations. In addition, Pearson's correlation analysis was conducted between directed functional connectivity and several clinical variables. Furthermore, receiver operating characteristic (ROC) analysis related to classification was performed in combination with VBM and GCD.

Results: In patients with cognitive decline, abnormal VBM and GCD (involving inflow and outflow of GCD) were noted in default mode network (DMN)-related areas and the cerebellum. GCD in the DMN midline core system, hippocampus, and cerebellum was closely correlated with the Mini- Mental State Examination and Functional Activities Questionnaire scores. In the ROC analysis combining VBM with GCD, the neuroimaging biomarker in the cerebellum was optimal for the early detection of MCI, whereas the precuneus was the best in predicting cognitive decline progression and AD diagnosis.

Conclusion: Changes in GM volume and directed functional connectivity may reflect the mechanism of cognitive decline. This discovery could improve our understanding of the pathology of AD and MCI and provide available neuroimaging markers for the early detection, progression, and diagnosis of AD and MCI.

Background: Studies have found synaptic plasticity damage to be an early marker of Alzheimer's disease (AD). RhoA/ROCK pathway is involved in the regulation of synaptic plasticity. Acupuncture can significantly improve the cognitive state of AD.

Objective: We aimed to use modern biological technology to detect the changes in synaptic plasticity and RhoA/ROCK pathway in SAMP8 mice, as well as the intervention effect of acupuncture.

Methods: Morris water maze and electrophysiological techniques were used in vivo to detect the changes in spatial memory and LTP of mice. Golgi Cox staining and CASEVIEWER2.1 software were used to quantitatively analyze the changes in the morphology and number of dendritic spines in the hippocampus of mice. The activity of RhoA and ROCK2 in the hippocampus of mice was detected, respectively, by pull-down technique and ELISA. WB technique was used to detect the protein expression of ROCK2 and phosphorylation level of MLC2, LIMK2, and CRMP2 in the hippocampus of mice.

Results: The neurobehavior and synaptic plasticity of 8-month-old SAMP8 mice were found to be significantly impaired. Acupuncture could improve the spatial learning and memory ability of SAMP8 mice, and partially prevent the reduction in the number of spines on the secondary branches of the apical dendrites in the hippocampus and the attenuation of LTP. The RhoA/ROCK pathway was significantly activated in the hippocampus of 8-month-old SAMP8 mice, and acupuncture had an inhibitory effect on it.

Conclusion: Acupuncture can improve synaptic plasticity by inhibiting the abnormal activation of the RhoA/ROCK pathway, and improve the spatial learning and memory ability of AD, so as to achieve the purpose of treating AD.

Background: The integrity of Locus Coeruleus can be evaluated in vivo using specific Magnetic Resonance Imaging sequences. While this nucleus has been shown to be degenerated both in post-mortem and in vivo studies in Alzheimer's Disease, for other neurodegenerative dementias such as Dementia with Lewy Bodies this has only been shown ex-vivo.

Objective: To evaluate the integrity of the Locus Coeruleus through Magnetic Resonance Imaging in patients suffering from Dementia with Lewy Bodies and explore the possible differences with the Locus Coeruleus alterations occurring in Alzheimer's Dementia.

Methods: Eleven patients with Dementia with Lewy Bodies and 35 with Alzheimer's Dementia were recruited and underwent Locus Coeruleus Magnetic Resonance Imaging, along with 52 cognitively intact, age-matched controls. Images were analyzed applying an already developed template-based approach; Locus Coeruleus signal was expressed through the Locus Coeruleus Contrast Ratio parameter, and a locoregional analysis was performed.

Results: Both groups of patients showed significantly lower values of Locus Coeruleus Contrast Ratio when compared to controls. A different pattern of spatial involvement was found; patients affected by Dementia with Lewy bodies showed global and bilateral involvement of the Locus Coeruleus, whereas the alterations in Alzheimer's Dementia patients were more likely to be localized in the rostral part of the left nucleus.

Conclusions: Magnetic Resonance Imaging successfully detects widespread Locus Coeruleus degeneration in patients suffering from Dementia with Lewy Bodies. Further studies, in larger cohorts and in earlier stages of the disease, are needed to better disclose the potential diagnostic and prognostic role of this neuroradiological tool.

Background: Traditional Chinese medicine (TCM) indicates that Alzheimer's disease (AD) is considered the consequence produced by Kidney Yang Deficiency Syndrome (KDS-Yang), which has similar clinical characteristics to glucocorticoid withdrawal syndrome. Ginsenoside Re (G-Re) has been found to ameliorate the symptoms and pathological impairments of AD. However, it's not clear whether G-Re could protect memory and synapse lesions against kidney deficiency dementia.

Methods: Subcutaneous injection of hydrocortisone for 14 days was used to produce KDS-Yang. On the 15th day, Aβ_25-35 peptide was injected into the intracerebroventricular (icv) of KDS-Yang rats. Spine density was analyzed by Golgi staining and the ultrastructural morphology of the synapse was detected using Transmission Electron Microscopy (TEM). Western blot was used to examine the expression of pS396, pS404, Tau-5, tGSK-3β, pS9GSK-3β, Syt, Syn I, GluA1, GluN2B, PSD93, PSD95, β₂-AR and pS346-b₂-AR.

Results: Hyperphosphorylation of tau in Aβ_25-35-injected rats with KDS-Yang was stronger than in Aβ_25-35-injected rats at the sites of Ser396 and Ser404. G-Re improved spatial memory damage detected by Morris water-maze (MWM), enhanced spines density, the thickness of postsynaptic density (PSD) and increased the expression of Syt, Syn I, GluA1, GluN2B, PSD93 and PSD95. Moreover, GRe decreased the hyperphosphorylation of β₂-AR at serine 346 in Aβ_25-35-injected rats with KDS-Yang.

Conclusion: KDS-Yang might exacerbate AD pathological lesions. Importantly, G-Re is a potential ingredient for protecting against memory and synapse deficits in kidney deficiency dementia.

Background: Intracerebral hemorrhage and cognitive decline are typical clinical presentations of cerebral amyloid angiopathy (CAA).

Objective: To determine whether magnetic resonance imaging (MRI) features differ between CAA with hemorrhagic versus cognitive onset.

Methods: In this retrospective study, sixty-one patients with CAA were classified by onset presentation of the disease: hemorrhage (n = 31) or cognitive decline (n = 30). The two groups were compared for MRI markers of small vessel disease, namely cerebral microbleeds (CMBs), cortical superficial siderosis, white matter hyperintensities (WMHs), enlarged perivascular spaces, cortical microinfarcts, and visual rating scales for cortical atrophy. In the patients with cognitive onset, further exploratory analyses investigated MRI markers according to cerebrospinal fluid (CSF) and neuropsychological profiles.

Results: Patients with cognitive onset showed a higher prevalence of CMBs (p < 0.001), particularly in temporal (p = 0.015) and insular (p = 0.002) lobes, and a higher prevalence of WMHs (p = 0.012). Within the cognitive onset group, 12 out of 16 (75%) patients had an Alzheimer's disease (AD) CSF profile but did not differ in MRI markers from those without AD pathology. Patients with cognitive onset displayed a multidomain profile in 16 out of 23 (70%) cases; patients with this profile showed increased WMHs and CMBs in parietal lobes compared with the amnestic group (p = 0.002) and dysexecutive group (p = 0.032), respectively.

Conclusion: Higher burdens of WMHs and CMBs, especially in temporal and insular lobes, are associated with the cognitive onset of CAA. MRI markers could help to shed light on the clinical heterogeneity of the CAA spectrum and its underlying mechanisms.

Aims: The study aimed to evaluate diagnostic values of circulating neurofilament light chain (NFL) levels in different types of dementia.

Background: Previous studies reported inconsistent change of blood NFL for different types of dementia, including Alzheimer's disease (AD), frontotemporal dementia (FTD), Parkinson's disease dementia (PDD) and Creutzfeldt-Jakob disease (CJD) and Lewy body dementia (LBD).

Objective: Meta-analysis was conducted to summarize the results of studies evaluating diagnostic values of circulating NFL levels in different types of dementia to enhance the strength of evidence.

Methods: Articles evaluating change in blood NFL levels in dementia and published before July 2022 were searched on the following databases (PubMed, Web of Science, EMBASE, Medline and Google Scholar). The computed results were obtained by using STATA 12.0 software.

Results: AD patients showed increased NFL concentrations in serum and plasma, compared to healthy controls (HC) (standard mean difference (SMD) = 1.09, 95% confidence interval (CI): 0.48, 1.70, I² = 97.4%, p < 0.001). In AD patients, higher NFL concentrations in serum and plasma were associated with reduced cerebrospinal fluid (CSF) Aβ_1-42, increased CSF t-tau, increased CSF p-tau, reduced Mini-Mental State Examination (MMSE) and decreased memory. Additionally, mild cognitive impairment (MCI) showed elevated NFL concentrations in serum and plasma, compared to HC (SMD = 0.53, 95% CI: 0.18, 0.87, I² = 93.8%, p < 0.001). However, in MCI, no significant association was found between NFL concentrations in serum, plasma and memory or visuospatial function. No significant difference was found between preclinical AD and HC (SMD = 0.18, 95% CI: -0.10, 0.47, I² = 0.0%, p = 0.438). FTD patients showed increased NFL concentrations in serum and plasma, compared to HC (SMD = 1.08, 95% CI: 0.72, 1.43, I² = 83.3%, p < 0.001). Higher NFL concentrations in serum and plasma were associated with increased CSF NFL in FTD. Additionally, the pooled parameters calculated were as follows: sensitivity, 0.82 (95% CI: 0.72, 0.90); specificity, 0.91 (95% CI: 0.83, 0.96). CJD patients showed increased NFL concentrations in serum and plasma, compared to HC. No significant difference in NFL level in serum and plasma was shown between AD and FTD (SMD = -0.03, 95% CI: -0.77, 0.72, I² = 83.3%, p = 0.003).

Conclusion: In conclusion, the study suggested abnormal blood NFL level in AD and MCI, but not in preclinical AD. FTD and CJD showed abnormal blood NFL levels.

Neurodegenerative diseases (NDDs) encapsulate conditions in which neural cell populations are perpetually degraded and nervous system function destroyed. Generally linked to increased age, the proportion of patients diagnosed with a NDD is growing as human life expectancies rise. Traditional NDD therapies and surgical interventions have been limited. However, recent breakthroughs in understanding disease pathophysiology, improved drug delivery systems, and targeted pharmacologic agents have allowed innovative treatment approaches to treat NDDs. A common denominator for administering these new treatment options is the requirement for neurosurgical skills. In the present narrative review, we highlight exciting and novel preclinical and clinical discoveries being integrated into NDD care. We also discuss the traditional role of neurosurgery in managing these neurodegenerative conditions and emphasize the critical role of neurosurgery in effectuating these newly developed treatments.

Background: An annual plant, Fenugreek (Trigonellafoenum-graecum L.) has well-known health care benefits in Ayurvedic and Chinese medicine. Its leaves and seeds have alkaloids, amino acids, caumarins, flavonoids, saponins, and other bioactive components. Various pharmacological properties such as antioxidants, hypoglycemic, and hypolipidemic have been attributed to fenugreek. Trigonelline, diosgenin, and 4- hydroxyisoleucine have shown neuroprotection against Alzheimer's disease, and the extract have also been reported to act as an anti-depressant, anti-anxiety, and also regulate cognitive functions. This review highlights various studies carried out on animals as well as on humans for the protective effect against Alzheimer's disease.

Methods: The data presented in this review is taken from popular search engines, viz, Google Scholar, PubMed, and Scopus. This review highlights the studies and clinical trials performed to show the protective effect of Fenugreek on neurodegenerative diseases with special reference to AD from 2005 to 2023.

Results: Fenugreek improves cognitive deficits by Nrf2-mediated antioxidative pathway and provides neuroprotection against amyloid-beta-induced mitochondria dysfunction. It enhances SOD and catalase activities and scavenges reactive oxygen species to protect the cellular organelle from oxidative stress. It normalizes the tubulin protein and improved axonal growth by regulating nerve growth factors. Fenugreek can also influence metabolism.

Discussion: Fenugreek significantly improves the pathological symptoms of neurodegenerative disease, especially AD and can be used as a therapeutic agent to control disease conditions as evidenced by the review of the literature.