Notes

Useful appearance of equilibrative along with concentrative nucleoside transporters within alveolar epithelial tissue.
Amnestic mild cognitive impairment (aMCI), a prodromal phase of Alzheimer's disease (AD), is characterized by episodic memory dysfunction, but inhibitory deficits have also been commonly reported. Time of day (TOD) effects have been confirmed in 1) healthy aging on cognitive processes such as inhibitory control, and 2) on behavior in AD (termed the sundowning effect), but no such research has addressed aMCI.

The present study examined the impact of TOD on the behavioral and electrophysiological correlates of inhibition in 54 individuals with aMCI and 52 healthy controls (HCs), all of morning chronotype.

Participants were randomly assigned to complete two inhibition tasks (Go-NoGo and Flanker) during their optimal (morning) or non-optimal (evening) TOD, while electroencephalography was recorded.

Both tasks elicited changes in N2 and P3 event-related potential (ERP) components, which commonly index inhibitory functioning. Analyses showed that the Go-NoGo difference in P3 amplitude was reduced in individuals with aMCI relative to HCs. Compared to HCs, the Flanker difference in P3 amplitude was also reduced and coincided with more errors in the aMCI group. Notably, these behavioral and ERP differences were exaggerated in the non-optimal TOD relative to the optimal TOD.

Findings confirm the presence of inhibition deficits in aMCI and provide novel evidence of sundowning effects on inhibitory control in aMCI. Results reinforce the need to consider the influences of TOD in clinical assessments involving individuals with aMCI.
Findings confirm the presence of inhibition deficits in aMCI and provide novel evidence of sundowning effects on inhibitory control in aMCI. Results reinforce the need to consider the influences of TOD in clinical assessments involving individuals with aMCI.
Tau oligomers are one of the most toxic species, displaying prion-like strains which have different conformations resulting in different tauopathies. Passive immunotherapy targeting different tau species is a promising therapeutic approach. Age is one of the greatest risk factors; however, most immunotherapy studies are done in young to middle-aged mice tauopathy models, which is not representative of the many clinical trials done with older humans with established tauopathies.

We utilized two different clones of tau oligomer monoclonal antibodies (TOMAs) in aged Htau and JNPL3 mouse models to investigate the potential of passive immunotherapy.

Aged mice received a single intravenous injection of 120 μg/animal of either TOMA1, TOMA3 clones or a non-specific IgG. Their cognitive functions were assessed one-week post-injection using Y-maze and novel object recognition tests. Brain tissues were analyzed using biochemical and immunological assays.

TOMA 1 and 3 rescues cognitive phenotypes in aged animals of great importance to further characterize these strains.
Modifiable risk factors exert crucial impact on dementia.

We sought to answer the question do two modifiable risk factors, schooling level and physical activity (PA), affect cognitive function similarly in each sex?

This cross-sectional study was conducted in 2019 and 2021, and the survey was applied to the residents of the metropolitan area of Santos, a seashore of Sao Paulo State. Four hundred and twenty-two participants (women = 254 and men = 168) were eligible. Baecke questionnaire for the elderly was applied for the classification as physically inactive (PI) or active (PA). Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR). Participants were also stratified by schooling status for both sexes.

Higher education had a sex-independent positive influence on MMSE and CDR (p < 0.001). PA influences positively MMSE in older women (PI 25±5 and PA 27±3, p < 0.03), but has no effect in older men (26±5 and 25±5, p > 0.05). Concordantly, older women who were PA (1.7 and 0 %) showed a lower prevalence of dementia compared with PI (6.2 and 2.1%), for mild and moderate respectively. Active older women had higher odds of improving the MMSE score (OR 1.093; 95% CI 1.008-1.186) than men (OR 0.97 (95% CI 0.896-1.051).

Education affects cognitive function equally in Brazilian elderly whereas older women are more responsive to the beneficial effects of PA for dementia than men.
Education affects cognitive function equally in Brazilian elderly whereas older women are more responsive to the beneficial effects of PA for dementia than men.
Recent innovative non-pharmacological interventions and neurostimulation devices have shown potential for application in the treatment of Alzheimer's disease (AD). These include photobiomodulation (PBM) therapy.

This pilot study assesses the safety, compliance with, and efficacy of a brain-gut PBM therapy for mild-to-moderate AD patients.

This double-blind, randomized, monocentric sham-controlled study started in 2018 and ended prematurely in 2020 due to the COVID-19 pandemic. Fifty-three mild-to-moderate AD patients were randomized, 27 in the PBM group and 26 in the sham group. All patients had 40 treatment sessions lasting 25 min each over 8 weeks and were followed for 4 weeks afterwards. Compliance with the treatment was recorded. Safety was assessed by recording adverse events (AEs), and efficacy was evaluated using neuropsychological tests.

The PBM therapy proved to be safe in regard to the number of recorded AEs (44% of the patients), which were balanced between the PBM and sham groups. AEs were mainly mild, and no serious AEs were reported. The majority of the patients (92.5%) were highly compliant, which confirms the feasibility of the PBM treatment. Compared to the sham patients, the PBM patients showed lower ADAS-Cog comprehension subscores, higher forward verbal spans, and lower TMT-B execution times, which suggests an improvement in cognitive functions.

This study demonstrates the tolerability of and patient compliance with a PBM-based treatment for mild-to-moderate AD patients. It highlights encouraging efficacy trends and provides insights for the design of the next phase trial in a larger AD patient sample.
This study demonstrates the tolerability of and patient compliance with a PBM-based treatment for mild-to-moderate AD patients. It highlights encouraging efficacy trends and provides insights for the design of the next phase trial in a larger AD patient sample.
Excessive oxidative stress may contribute to neurodegeneration by leading to protein aggregation and mitochondrial dysfunction. Uric acid (UA) is an important endogenous antioxidant that protects against oxidative stress, yet its exact role in neurodegeneration remains unclear.

To explore the performance of serum UA in neurodegenerative disorders.

A total of 839 controls and 840 patients, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), motor neuron disease (MND), Creutzfeldt-Jakob disease (CJD), and mixed dementia (MixD) were enrolled. Fasting serum UA levels were measured in all participants and compared between patients and controls. Linear regression models were utilized to explore possible relationships of serum UA with cognition, disease duration, age, and age of onset.

Compared to controls (355.48 ± 85.38 μmol/L), serum UA was significantly lower in AD (291.29 ± 83.49 μmol/L, p < 0.001), PD (286.95 ± 81.78 μmol/L, p < 0.001), PSP (313.32 ± 88.19 μmol/L, p < 0.001), FTD (313.89 ± 71.18 μmol/L, p = 0.001), and DLB (279.23 ± 65.51 μmol/L, p < 0.001), adjusting for confounding factors including age, gender, education, etc. In addition, serum UA was positively correlated with cognitive levels in all patients (Mini-Mental State Examination r = 0.136, p = 0.001; and Montreal Cognitive Assessment Scale r = 0.108, p = 0.009).

Decreased levels of serum UA were correlated with AD, PD, PSP, FTD, and DLB, offering significant potential as a promisingly relevant, less-invasive marker of multiple neurodegenerative disorders.
Decreased levels of serum UA were correlated with AD, PD, PSP, FTD, and DLB, offering significant potential as a promisingly relevant, less-invasive marker of multiple neurodegenerative disorders.
Alzheimer's disease (AD) was the main cause of dementia in an aging society; unfortunately, there is no effective treatment for AD now. Meditation has been reported to thicken the cerebral cortex, and gamma wave at a frequency of 40 hertz (Hz) was recorded during the meditation process from the brain. Previous study showed that non-invasive scintillation gamma frequency oscillation increased the space in recognition and memory of auditory cortex hippocampal gyrus in AD mice model. However, the AD-related molecular change by exposure of 40 Hz gamma frequency in brain cells was still unclear.

We investigated the AD-related molecular change by exposure of 40 Hz gamma frequency in SH-SY5Y cells.

We designed the light and sound generators at 40 Hz gamma frequency for this study. SH-SY5Y cells were exposed to sound or light of 40 Hz gamma frequency, respectively. The concentrations of amyloid-β40 (Aβ40) and amyloid-β42 (Aβ42) were quantified by enzyme-linked immunosorbent assay. The protein levels were examined by Western blotting. The aggregation of Aβ42 was examined by thioflavin T assay.

Our results showed that the secretion of Aβ, phosphorylation of AKT, mTOR, and tau, and aggregation of Aβ42 were significantly inhibited by 40 Hz gamma frequency in SH-SY5Y cells. The phosphorylation of 4E-BP1, downstream of mTOR, was induced by 40 Hz gamma frequency in SH-SY5Y cells.

Our study showed 40 Hz gamma frequency involved in the inhibition of secretion and aggregation of Aβ and inhibition of p-Tau protein expression through the mTOR/4E-BP1/Tau signaling pathway.
Our study showed 40 Hz gamma frequency involved in the inhibition of secretion and aggregation of Aβ and inhibition of p-Tau protein expression through the mTOR/4E-BP1/Tau signaling pathway.
Despite tremendous advancements in the field, our understanding of mild cognitive impairment (MCI) and Alzheimer's disease (AD) among Mexican Americans remains limited.

The aim of this study was to characterize MCI and dementia among Mexican Americans and non-Hispanic whites.

Baseline data were analyzed from n = 1,705 (n = 890 Mexican American; n = 815 non-Hispanic white) participants enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD).

Among Mexican Americans, age (OR = 1.07), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.01) were associated with dementia, but none of these factors were associated with MCI. DNA-PK inhibitor Among non-Hispanic whites, male gender (OR = 0.33), neighborhood deprivation (OR = 1.34), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.03) were associated with MCI, while depression (OR = 1.09) and APOEɛ4 genotype (OR = 4.38) were associated with dementia.

Findings from this study revealed that the demographic, clinical, sociocultural and biomarker characteristics of MCI and dementia are different among Mexican Americans as compared to non-Hispanic whites.
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