Journal of Alzheimer's Disease最新文献

BackgroundCognitive impairment is increasingly prevalent in younger populations. The interplay between environmental exposures like noise and genetic susceptibility in dementia etiology remains unclear. This study investigated the combined effects of work-related cumulative noise exposure (WCNE) and genetic polymorphisms on cognitive performance.ObjectiveTo examine the relationships among WCNE, genetic factors (APOE rs429358/rs7412 and PS-1 rs165932), and lower cognitive performance (LCP), and to analyze the potential interaction.MethodsThis study included 523 workers from a health surveillance cohort in western China. WCNE was assessed for each participant. Genotyping was performed for APOE (rs429358/rs7412) and PS-1 (rs165932) polymorphisms. Cognitive function was evaluated via Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The individual and combined effects of WCNE and genetic factors on LCP were analyzed.ResultsAPOE rs429358/rs7412 were not significantly associated with LCP. The PS-1 rs165932T allele (PS-1T) was associated with LCP (p < 0.05). The adjusted odds ratios (aORs) for LCP (evaluated by MMSE and MoCA) in the PS-1T group were 2.443 (95% CI: 1.149-5.195) and 2.065 (95% CI: 1.091-3.906), respectively. Age and WCNE had an interaction effect on the LCP for both MMSE and MoCA (p < 0.05), while PS-1T had an effect modification on the relationship between WCNE and LCP (p < 0.05).ConclusionsThese findings highlight the urgent need to identify and mitigate noise exposure risks in vulnerable populations. These findings also provide evidence for further mechanistic studies exploring how noise, aging, and genetic susceptibility contribute to cognitive impairment through underlying biological mechanisms.

BackgroundThe retrosplenial cortex (RSC) is a cortical area that functions as a key component of the core network of brain regions involved in cognitive functions such as episodic memory, navigation, and planning. The RSC is capable of theta rhythm generation and, like the hippocampus, could be compromised in neurological diseases such as Alzheimer's disease (AD). Importantly, detecting early changes in RSC of transgenic animals could be translated into non-invasive biomarkers that can detect preclinical stages of AD and related dementias.ObjectiveOur aim in the present study was to evaluate molecular and functional alterations in the RSC of very young 3xTg-AD mice (1-month-old).MethodsImmunohistochemistry, anterograde viral tracer using an adeno-associated virus, western blotting, and electrophysiology were all carried out.ResultsOur results show significant accumulation of intracellular amyloid-β (Aβ) and hyperphosphorylated tau (pTau) in principal neurons from 1-month-old 3xTg-AD mice, which correlates with GSK3β activation and tau phosphorylation at serine 396. Coincidentally, oscillatory activity from the RSC is altered in the young 3xTg-AD mice. Specifically, we found that theta frequency is significantly higher in the transgenic animals.ConclusionsIn summary, our results suggest that the early accumulation of intracellular Aβ may affect the excitability of the RSC network, possibly due to changes in pTau resulting from GSK3β activation.

BackgroundEmotion recognition ability is essential for social cognition, enabling humans to interpret and respond to emotion-related cues. However, so far, it is not known how underlying cognitive deficits, face processing and emotional intelligence are associated with emotion recognition, particularly in patients with mild cognitive impairment (MCI).ObjectiveTo examine emotion recognition performance in patients with MCI and the associations between emotion recognition, face processing, emotional interference, and emotional intelligence.Methods60 participants (patients with MCI = 30, healthy controls (HC) = 30), aged 50-86 years (M = 66.8, SD = 8.66), completed the Emotion Composite Task (ECT), Facial Composite Task (FCT), and Emotion Stroop Task. Emotional intelligence (EI) was assessed using the Trait Emotional Intelligence Questionnaire (TEIQUE).ResultsOverall, patients with MCI performed worse on the ECT than healthy controls (β = -0.36, p = 0.207, FDR p = 0.311), although this difference did not reach significance. Emotion-specific analysis showed that anger recognition was particularly impaired in patients with MCI (β = -0.86, p < 0.001). Better face processing ability was associated with better anger recognition (β = 0.28, p < 0.05), and higher EI with better overall emotion recognition (β = 0.62, p < 0.05).ConclusionsAlthough overall emotion recognition performance did not significantly differ between groups, patients with MCI showed selective impairments in recognizing anger. Face processing and emotional intelligence were associated with better emotion recognition, suggesting that patients with MCI who have stronger perceptual and socio-emotional skills preserve their emotion recognition abilities more effectively.

BackgroundCognitive decline represents a major challenge in aging populations. Probiotics have been proposed to influence cognitive function through gut-brain interactions, but clinical findings remain inconsistent.ObjectiveThis study evaluated the effects of probiotic supplementation on cognitive function as the primary outcome, and on BDNF levels, inflammatory markers, and oxidative stress biomarkers as secondary outcomes in adults aged 50 years and older.MethodsA systematic search of PubMed, EBSCO, ProQuest, and Google Scholar was conducted through 1 May 2024 using predefined search terms related to probiotics, cognitive function, BDNF, inflammation, and antioxidant activity. Study quality was assessed using the RoB 2 tool. Meta-analyses were performed using random-effects models, and publication bias was explored using Egger's test where study counts permitted.ResultsSixteen studies demonstrated significant improvement in cognitive function among participants receiving probiotics compared to placebo. Cognitive function, measured using the Mini-Mental State Examination (MMSE), yielded a standardized mean difference (SMD) of 0.747 (95% CI 0.307-1.186) which corresponds to moderate-to-large effects. In comparison, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) showed significant results with an SMD of 0.340 (95% CI 0.032-1.366) which corresponds to small-to-moderate effects. Probiotics also led to significant changes in several biochemical parameters, including BDNF, TNF-α, 8-OHdG, IL-6, IL-10, MDA, TAC, and GSH. Multi-strain probiotics showed better results compared to single-strain.ConclusionsProbiotic supplementation may offer modest cognitive benefits in aging populations, particularly in studies enrolling cognitively impaired individuals, but substantial heterogeneity and limited biomarker evidence restrict the certainty of these findings. Larger, longer-duration, and standardized trials are needed to clarify the clinical relevance and potential biological pathways underlying probiotic effects on cognition.

BackgroundPlasma sphingomyelin (SM), an established biomarker of white matter hyperintensity (WMH), has recently been implicated in Alzheimer's disease (AD) risk, but its role in cognitive decline remains unclear.ObjectiveTo examine whether plasma SM (d18:1/24:0) is associated with incident AD risk and to clarify its relationships with AD pathology, neuroimaging, and cognition in non-demented adults.MethodsWe included 476 non-demented participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Kaplan-Meier analysis assessed AD progression, with group comparisons by log-rank test. Cox proportional hazards models estimated hazard ratios and 95% confidence intervals. Multiple linear regression and mixed-effects models evaluated associations of SM with cerebrospinal fluid biomarkers, neuroimaging measures, and cognition. A causal mediation analysis was performed using 10,000 bootstrapped iterations to evaluate the intermediary role of AD pathology in cognitive function.ResultsParticipants with higher levels of SM (d18:1/24:0) exhibited decreased AD risk. Plasma SM (d18:1/24:0) presented positive associations with Rey Auditory Verbal Learning Test (RAVLT-immediate), amyloid-β pathology, ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism and brain volume, and negative associations with tau pathology, WMH-V, and ventricular volume. The association between SM (d18:1/24:0) and verbal memory was partially mediated by amyloid and tau pathology, FDG-PET, and hippocampal-V.ConclusionsThis study suggests that lower plasma SM (d18:1/24:0) levels are associated with an increased risk of AD. Plasma SM (d18:1/24:0) is closely related to cognitive performance, neuroimaging markers, and AD pathology, and its association with verbal memory may be partially mediated by AD pathology.

BackgroundAmyloid accumulation and degeneration of the cholinergic white matter pathways are key factors in early Alzheimer's disease pathogenesis and progression. However, the relationship between them remains unclear.ObjectiveTo investigate the association between amyloid accumulation, the integrity of cholinergic white matter pathways, and cognitive performance.MethodsThis cross-sectional study recruited 109 individuals, including 37 controls with normal cognition and 72 patients with early Alzheimer's disease. All participants underwent neuropsychological testing: the Mini-Mental Status Examination (MMSE), Clinical Dementia Rating scale with sum of box (CDR-SB), and verbal fluency tests. Cholinergic white matter integrity and amyloid burden were assessed through diffusion tensor imaging study (DTI) and amyloid positron emission tomography (PET). Stepwise linear regression analyses were performed. Partial correlations between amyloid burden and cholinergic integrity were also evaluated according to apolipoprotein E4 (APOE4) carrier status.ResultsAcross all participants, amyloid burden and cholinergic integrity were independently associated with all cognitive performances. In subgroup analysis, amyloid burden was associated with MMSE only in the early Alzheimer's disease group (p = 0.012). Cholinergic integrity was significantly associated with all cognitive performances in the early Alzheimer's disease group (p < 0.05) but not in the control group. Amyloid burden remained significantly correlated with cholinergic integrity only in APOE4 noncarriers (p < 0.05) but not in APOE4 carriers.ConclusionsCholinergic white matter integrity, the severity of which is associated with amyloid burden, may be a specific imaging marker in early-stage Alzheimer's disease. In this study, this phenomenon was more pronounced in APOE4 noncarriers.

BackgroundElevated blood pressure (BP) is considered a risk factor for cognitive disorders. This study examined the continuous relationship between 2-year mean systolic BP (SBP) and incident cognitive disorders in a large, real-world primary care cohort.ObjectiveTo evaluate the associations of 2-year mean SBP with incident cognitive impairment in a 'real-world' clinical observational dataset.MethodsWe conducted a longitudinal analysis of electronic health records (EHR) from primary care patients aged 50 or older. Patients were included if they had ≥2 SBP measurements and no cognitive disorder diagnosis prior to or within 3 years of their first included SBP measurement. Exposure was the average SBP in the two years following the first measurement. We estimated associations between (continuous) average SBP and incident cognitive impairment using a Cox model. Records from 160,052 patients were included in the analysis.ResultsIn our study, SBP ≥ 140 mmHg is not associated with a statistically significant difference in cognitive disorder risk compared to lower SBP (<120 and 120-140 mmHg). In the ages 60-69 group, SBP 135 mmHg is the lowest SBP at which a significantly decreased risk for cognitive disorders was observed (HR, 0.84; 95% CI, 0.82-0.89; p < 0.05). Among unmedicated individuals, 136 mmHg SBP was the lowest SBP at which a statistically significant association with decreased cognitive disorder risk was observed (HR, 0.92; 95% CI, 0.87-1.00; p < 0.05).ConclusionsThe association between SBP and cognitive disorder risk varies by age and BP medication use. This highlights the need for individualized BP targets to mitigate cognitive impairment.

BackgroundMild cognitive impairment (MCI), as an early manifestation of Alzheimer's disease and dementia, not only diminishes quality of life for the elderly but also imposes a substantial disease burden on society.ObjectiveThis study aims to investigate the epidemiological characteristics and influencing factors of MCI among rural elderly, and to utilize life expectancy (LE) and healthy life expectancy (HLE) as metrics to assess quality of life.MethodsThis study involved 14,549 participants aged 60 years and older from the Henan Rural Cohort Study. Cognitive function was assessed using the Mini-Mental State Examination. LE and HLE were calculated using the Sullivan method. A meta-analysis, which included 16 published studies, was conducted to validate the findings from the cross-sectional survey.ResultsThe crude and age-standardized prevalence of MCI were 32.96% and 34.14%, respectively. The prevalence of MCI was increased with age and was significantly higher among women than men. The results of the meta-analysis support the cross-sectional findings. Older age, being women, living alone, low income, low-level physical activity, insufficient fruit and vegetable intake, night sleep duration ≥8 h, hypertension, dyslipidemia, T2DM, cardiovascular diseases, depression, anxiety, and underweight are associated with an increased risk of MCI. The HLE/LE ratio declined with increasing age, and the HLE/LE ratio of women in each age group is lower than men.ConclusionsMCI is highly prevalent with multiple influencing factors. The HLE/LE ratio of elderly could increase from the reduction of MCI. Future research should focus on targeted screening and intervention approaches for MCI.

BackgroundWith the aging population, the number of Alzheimer's disease (AD) patients has been increasing annually, creating an urgent need for AD therapeutic drugs. Donepezil combined with nimodipine (DN) has demonstrated therapeutic potential in the treatment of AD, but its mechanism of action remains unclear.ObjectiveTo reveal the mechanism of DN in the treatment of AD rats.MethodsThe AD rat model was established and evaluated by behavioral experiments and pathology. The therapeutic mechanism of DN in AD treatment was investigated through lipidomics and hippocampal metabolomics analyses based on ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF/MS).ResultsThe learning and memory ability of AD rats can be improved after DN treatment. Significant changes were observed in 40 serum lipid metabolites and 19 hippocampal metabolites. These metabolites are mainly involved in glycerophospholipid metabolism, sphingolipid metabolism, amino acid metabolism, unsaturated fatty acid metabolism and other processes in AD rats.ConclusionsDN could improve cognitive function and nerve damage in AD rats. It may plays a therapeutic role in AD rats by regulating cholinergic damage, Ca²⁺ overload, oxidative stress, neuroinflammation, and energy deficiency caused by metabolic disorders, which has practical significance for further research and clinical application of DN.

BackgroundWith recent advances in disease-modifying therapies for Alzheimer's disease (AD), demand for confirmatory biomarker testing such as via cerebrospinal fluid (CSF) analysis or amyloid positron emission tomography (PET) will increase considerably for diagnosis.ObjectiveTo assess the current capacity and estimating the anticipated future need of AD confirmatory testing in the United States (US).MethodsA population-based decision tree model was employed to simulate the AD diagnostic pathway for patients presenting with symptoms of mild cognitive impairment or mild dementia in primary and secondary care in the US. All patients were assumed to be enrolled in Medicare. The study was conducted from the US payer's perspective over a 5-year period. Four scenarios assessed the impact of different utilization patterns: (1) reference scenario (current use in AD diagnostic pathway: < 1% amyloid-PET; 3.5% CSF analysis); (2) increased CSF analysis utilization scenario (50% utilization); (3) amyloid-PET only; and (4) CSF analysis only.ResultsScenario 1 fails to meet the growing demand for AD confirmatory testing (assumed annual care-seeking rate of 50%), with approximately 0.3% of all amyloid-β-positive patients receiving a timely and accurate diagnosis with amyloid-PET, and 1.7% with CSF analysis. Scenarios 2 and 4 resulted in the highest proportion of accurate and timely diagnoses for amyloid-β-positive patients (24.8% and 44.6%, respectively) versus 15.1% of patients in scenario 3.ConclusionsIt is imperative to address capacity issues for AD confirmatory testing to facilitate timely diagnosis and initiation of amyloid-targeting therapies. Increasing CSF analysis utilization has the capacity to meet this growing demand.