Watersmaher8584

Extensive studies put forward the association between Alzheimer's disease (AD) and psychiatric disorders; however, it remains unclear whether these associations are causal.

We aimed to assess the potential causal relationship between major psychiatric disorders and AD.

A bidirectional two-sample Mendelian randomization (MR) was applied to evaluate potential causality between five psychiatric disorders and AD by selecting the single-nucleotide polymorphisms from the genome-wide association studies as instrumental variables. Inverse-variance weighted (IVW) method was used as the main analyzing approach to estimate possible causal effects, alternative methods including MR-Egger, the MR pleiotropy residual sum and outlier, and leave-one-out analysis method were implemented as sensitivity analyzing approaches to ensure the robustness of results.

All forward and reverse MR analyses consistently suggested absent causal relations between psychiatric disorders and AD risk [forward IVW ORADHD, 1.030, 95% CI, 0.908-1.168, p = 0.674; ORanxiety disorders, 0.904, 95% CI, 0.722-1.131, p = 0.377; ORASD, 0.973, 95% CI, 0.746-1.272, p = 0.846; ORBIP, 1.033, 95% CI, 0.925-1.153, p = 0.564; and ORschizophrenia, 1.039, 95% CI, 0.986-1.095, p = 0.156; reverse IVW ORADHD, 0.993, 95% CI, 0.954-1.034, p = 0.746; ORanxiety disorders, 1.000, 95% CI, 0.999-1.000, p = 0.898; ORASD, 1.001, 95% CI, 0.962-1.042, p = 0.949; ORBIP, 0.997, 95% CI, 0.966-1.028, p = 0.831; and ORschizophrenia, 1.013, 95% CI, 0.978-1.051, p = 0.466].

There is no significant evidence supporting the causal association between the five major psychiatric disorders and AD.

There is no significant evidence supporting the causal association between the five major psychiatric disorders and AD.

Alzheimer's disease (AD) is a biologically heterogenous disease. Previous studies have reported the existence of various AD subtypes, and the various clinical features of the subtypes. However, inconsistent results have been obtained.

To clarify the clinical characteristics of the various AD subtypes, by classifying probable AD into subtypes based on magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) findings.

A total of 245 patients with probable AD were classified into the typical AD (TAD) subtype, limbic-predominant (LP) subtype, hippocampal-sparing (HS) subtype, and minimal-change (MC) subtype, based on the presence of medial temporal lobe atrophy on MRI and posterior cerebral hypoperfusion on SPECT. Demographics, including age, sex, body mass index, disease duration, education years, comorbidities, frailty, leisure activity, and neuropsychological findings were compared between the AD subtypes.

he frequency of TAD, LP, HS, and MC subtypes was 49%, 20%, 18%, and 13%, respectively. Patients with the LP subtype were older and characterized by fewer major comorbidities, higher frailty, and slower progression of disease. Patients with the HS subtype were younger and characterized by shorter disease duration, lower frailty, and preserved memory, but had prominent constructional dysfunction. Patients of the MC subtype were characterized by shorter disease duration, lower education level, less leisure activity, less impaired memory and orientation, and slower progression.

Patients with different AD subtypes differed in their demographic and clinical features. The characterization of patients' AD subtypes may provide effective support for the diagnosis, treatment, and care of AD patients.

Patients with different AD subtypes differed in their demographic and clinical features. The characterization of patients' AD subtypes may provide effective support for the diagnosis, treatment, and care of AD patients.

Mechanistic studies in animal models implicate a role for saturated fatty acids in neurodegeneration, but validation of this finding in human studies is still lacking.

We investigated how cerebrospinal levels of sphingomyelins (SM) and phosphatidylcholine (PC)-containing saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids associate with total tau and phosphorylated tau (p-tau).

Cerebrospinal fluid (CSF) lipids were measured in two cohorts, a discovery and a confirmation cohort of older non-demented individuals from the University of Southern California and Huntington Medical Research Institutes cohorts. Lipid analysis was performed using hydrophilic interaction liquid chromatography, and individual PC and SM lipid species were measured using tandem mass spectrometry. In addition, CSF levels of Aβ42, total tau, and p-tau-181 were measured using an MSD multiplex assay.

The discovery cohort (n = 47) consisted of older individuals and more females compared to the confirmation cohort (n = 46). Notwithstanding the age and gender differences, and a higher p-tau, Aβ42, and LDL-cholesterol in the discovery cohort, CSF concentrations of dipalmitoyl-PC (PC32a0) were significantly associated with p-tau in both cohorts. Similarly, total saturated PC but not mono or polyunsaturated PCs correlated with p-tau concentrations in both cohorts.

Saturated PC species in CSF associate with early markers of neurodegeneration and are potential early disease progression biomarkers. We propose mechanisms by which saturated PC may promote tau hyperphosphorylation.

Saturated PC species in CSF associate with early markers of neurodegeneration and are potential early disease progression biomarkers. We propose mechanisms by which saturated PC may promote tau hyperphosphorylation.

Early-life Pb exposure can cause behavioral and cognitive problems and induce symptoms of hyperactivity, impulsivity, and inattention in children. Studies showed that blood lead levels were highly correlated with neuropsychiatric disorders, and effects of neurotoxicity might persist and affect the incidence of neurodegenerative diseases, for example Alzheimer's disease (AD).

To explore possible mechanisms of developmental Pb-induced neuropsychiatric dysfunctions.

Children were divided into low blood lead level (BLL) group (0-50.00μg/L) and high BLL group (> 50.00μg/L) and blood samples were collected. learn more miRNA array was used to testify miRNA expression landscape between two groups. Correlation analysis and real-time PCR were applied to find miRNAs that altered in Pb and neuropsychiatric diseases. Animal models and cell experiments were used to confirm the effect of miRNAs in response to Pb, and siRNA and luciferase experiments were conducted to examine their effect on neural functions.

miRNA array data and correlation analysis showed that miR-34b was the most relevant miRNA among Pb neurotoxicity and neuropsychiatric disorders, and synapse-associated membrane protein 2 (VAMP2) was the target gene regulating synapse function. In vivo and in vitro studies showed Pb exposure injured rats' cognitive abilities and induced upregulation of miR-34b and downregulation of VAMP2, resulting in decreases of hippocampal synaptic vesicles. Blockage of miR-34b mitigated Pb's effects on VAMP2 in vitro.

Early-life Pb exposure might exert synapse-toxic effects via inhibiting VAMP2 mediated by upregulation of miR-34b and shed a light on the underlying relationship between Pb neurotoxicity and developmental neuropsychiatric disorders.

Early-life Pb exposure might exert synapse-toxic effects via inhibiting VAMP2 mediated by upregulation of miR-34b and shed a light on the underlying relationship between Pb neurotoxicity and developmental neuropsychiatric disorders.

Visual short-term memory (VSTMT) and visual attention (VAT) exhibit decline in the Alzheimer's disease (AD) continuum; however, network disruption in preclinical stages is scarcely explored.

To advance our knowledge about brain networks in AD and discover connectivity alterations during VSTMT and VAT.

Twelve participants with AD, 23 with mild cognitive impairment (MCI), 17 with subjective cognitive decline (SCD), and 21 healthy controls (HC) were examined using a neuropsychological battery at baseline and follow-up (three years). At baseline, the subjects were examined using high density electroencephalography while performing a VSTMT and VAT. For exploring network organization, we constructed weighted undirected networks and examined clustering coefficient, strength, and betweenness centrality from occipito-parietal regions.

One-way ANOVA and pair-wise t-test comparisons showed statistically significant differences in HC compared to SCD (t (36) = 2.43, p = 0.026), MCI (t (42) = 2.34, p = 0.024), and AD group (t (31) = 3.58, p = 0.001) in Clustering Coefficient. Also with regards to Strength, higher values for HC compared to SCD (t (36) = 2.45, p = 0.019), MCI (t (42) = 2.41, p = 0.020), and AD group (t (31) = 3.58, p = 0.001) were found. Follow-up neuropsychological assessment revealed converge of 65% of the SCD group to MCI. Moreover, SCD who were converted to MCI showed significant lower values in all network metrics compared to the SCD that remained stable.

The present findings reveal that SCD exhibits network disorganization during visual encoding and retrieval with intermediate values between MCI and HC.

The present findings reveal that SCD exhibits network disorganization during visual encoding and retrieval with intermediate values between MCI and HC.

Amyloid-β (Aβ) fibrils induce cognitive impairment and neuronal loss, leading to onset of Alzheimer's disease (AD). The inhibition of Aβ aggregation has been proposed as a therapeutic strategy for AD. Pristine C60 has shown the capacity to interact with the Aβ peptide and interfere with fibril formation but induces significant toxic effects in vitro and in vivo.

To evaluate the potential of a series of C60 multiadducts to inhibit the Aβ fibrillization.

A series of C60 multiadducts with four to six diethyl malonyl and their corresponding disodium-malonyl substituents were synthesized as individual isomers. Their potential on Aβ fibrillization inhibition was evaluated in vitro, in cellulo, and silico. Antioxidant activity, acetylcholinesterase inhibition capacity, and toxicity were assessed in vitro.

The multiadducts modulate Aβ fibrils formation without inducing cell toxicity, and that the number and polarity of the substituents play a significant role in the adducts efficacy to modulate Aβ aggregation. The molecular mechanism of fullerene-Aβ interaction and modulation was identified. Furthermore, the fullerene derivatives exhibited antioxidant capacity and reduction of acetylcholinesterase activity.

Multiadducts of C60 are novel multi-target-directed ligand molecules that could hold considerable promise as the starting point for the development of AD therapies.

Multiadducts of C60 are novel multi-target-directed ligand molecules that could hold considerable promise as the starting point for the development of AD therapies.

Self and informant (proxy or study partner) reports of everyday cognitive functioning have been shown to be associated with incipient neurodegenerative disease. The 20-item Cognitive Change Index (CCI) and the 39-item Measurement of Everyday Cognition (ECog) were each developed to characterize early subjective changes in cognitive function.

We examined the relationship between CCI and ECog self and informant-based evaluations to determine content overlap and provide a co-calibration for converting between these widely used instruments.

950 participants (57.1% female, mean age = 71.2 years) from ADNI and the Indiana ADRC with self-based evaluations and 279 participants (60.9% female, mean age = 71.8 years) with informant-based evaluations (Indiana ADRC) were included. Analyzed variables for the CCI and ECog included domain mean scores, memory domain total scores, and total scores for all items. Spearman correlations, regression analyses, and frequency distributions were used to assess the relationship between CCI and ECog.