Decline In Cognitive Function Research Articles

An IoT Approach Enhanced with AI Capabilities for Predictive Neurology in Smart Homes

<p dir="ltr"><span>The integration of Artificial Intelligence (AI) and Internet of Things (IoT) offers remarkable chances for improving healthcare in smart home environments. In order to anticipate and observe neurological disorders, the study explores the use of IoT devices along with AI analytics. The goal is to identify early signs of any decline in cognitive functions or neurodegenerative conditions such as Alzheimer’s or Parkinson’s. The research emphasises on examining a framework for predictive neurology while it faces challenges associated with real-time data processing and prediction precision. The outcomes should result in a smart home ecosystem development that focuses on healthcare interventions and enhances life quality. This paper explores a multi-layered architecture, including an exploratory phase to analyse user needs, a developmental phase to design and integrate IoT devices, Machine Learning algorithms, and cloud architectures, as well as a validation phase to undergo rigorous testing in simulated environments to evaluate performance metrics.</span></p><div><span><br /></span></div>

C/EBPβ in Alzheimer's Disease: An Integrative Regulator of Pathological Mechanisms.

Alzheimer's disease (AD) stands as one of the most prevalent neurodegenerative disorders, characterized by a progressive decline in cognitive function, neuroinflammation, amyloid-beta (Aβ) plaques, and neurofibrillary tangles (NFTs). With the global aging population, the incidence of AD continues to rise, yet current therapeutic strategies remain limited in their ability to significantly alleviate cognitive impairments. Therefore, a deeper understanding of the molecular mechanisms underlying AD is imperative for the development of more effective treatments. In recent years, the transcription factor C/EBPβ has emerged as a pivotal regulator in several pathological processes of AD, including neuroinflammation, lipid metabolism, Aβ processing, and tau phosphorylation. Through intricate post-translational modifications, C/EBPβ modulates these processes and may influence the progression of AD on multiple fronts. This review systematically explores the multifaceted roles of C/EBPβ in the pathogenesis of AD, delving into its crucial involvement in neuroinflammation, Aβ production, tau pathology, and lipid metabolism dysregulation. Furthermore, we critically assess therapeutic strategies targeting C/EBPβ, examining the challenges and opportunities in regulating this factor. By synthesizing the latest research findings, we offer a more comprehensive understanding of the role of C/EBPβ in AD and discuss its potential as a therapeutic intervention target.

Oral Frailty Indicators and Cardio- and Cerebrovascular Diseases in Older Age:A Systematic Review

Oral health indicators may contribute to the oral frailty phenotype, an age-related gradual loss of oral function together with a decline in cognitive and physical functions. The present systematic review synthetized current knowledge on the associations of oral frailty indicators and major cardio- and cerebrovascular diseases in older age, including coronary heart disease (CHD), arteriosclerosis, arrhythmias, hypertension, cardiovascular diseases not otherwise specified (NOS), and stroke. The study is registered on PROSPERO-(CRD42023397932). From database inception to March 31, 2024, six different electronic databases were consulted assessing the eligibility of 50,005 records against the inclusion criteria and 20 studies on 226,025 older adults were included. Five different indicators of oral frailty (number of teeth, periodontal disease, general oral health, dry mouth, and bite force) were related to cardio- and cerebrovascular diseases. The number of teeth was associated with all the outcomes except hypertension, followed by periodontal disease associated with CHD, arteriosclerosis, hypertension, and stroke. General oral health and dry mouth were associated with CHD/arrhythmias and CHD/stroke, respectively. Finally, bite force was associated only with cardiovascular diseases NOS. The present findings could help to assess the contribution of each oral frailty indicator to the development of cardio- and cerebrovascular diseases in older age.

Effect of Social Restriction Due to the COVID-19 Pandemic on Activity of Daily Living and Disease Severity of Patients With Alzheimer Disease: Sub-analysis of a Double-blinded Noninferiority Study of Donepezil Patches and Donepezil Tablets.

We previously reported that social restrictions due to the COVID-19 pandemic led to a decline in cognitive function in patients with Alzheimer disease (AD). Here, we assessed the effects of COVID-19 restrictions on the activities of daily living (ADL) and disease severity in patients by comparing them to a control group. We examined the impact on ADL, evaluated using disability assessment for dementia (DAD), and disease severity, evaluated using the ABC dementia scale, in patients with mild-to-moderate AD. We conducted a post hoc subgroup analysis of a double-blinded, noninferiority study of donepezil 27.5mg patches and donepezil hydrochloride 5mg tablets (JapicCTI-194582). After showing the noninferiority of both treatments, we combined the data from both groups for analysis. The subpopulation of the per-protocol set grouped by completing the double-blinded evaluation before and on/after the mild lockdown was balanced (n=136 and n=120). Patient demographics were similar between the subgroups. The decline in the DAD and ABC dementia scale scores [least-squares mean (SE)] was ameliorated by social restriction [-3.810 (0.743) and -1.871 (0.697) and -1.147 (0.285) and -0.419 (0.267), respectively (not significant)]. Normalcy and expectation biases can affect the evaluation of ADL and disease severity by caregivers under high stress and deterioration of mental conditions.

Longitudinal associations between late-life depression, cerebrovascular disease and cognition.

Depression and vascular disease can both be risk factors for cognitive decline. This study assessed whether indicators of vascular disease are associated with depression over time, and whether depression is associated with cognition independent of vascular disease. Participants were 1032 community-dwelling, older adults from the Sydney Memory and Ageing Study. Depressive symptoms were measured on the 15-item Geriatric Depression Scale, and depression trajectories were classified using latent class growth modelling. Global cognition and individual cognitive domains were assessed. Indicators of vascular disease were history of stroke or transient ischaemic attack (TIA) and total white matter hyperintensities (TWMH). Generalised linear mixed modelling assessed whether vascular markers were associated with change in depressive symptoms over time. Linear mixed modelling examined relationships between depression, vascular disease indicators, and cognition. History of stroke/TIA or TWMH did not predict depression over time (p = 0.11 and p = 0.70). Baseline stroke/TIA history was associated with a decline in attention over time (b = -0.05, p = 0.04). Significant differences between latent depression trajectories classes in cognitive decline were observed, with participants who became depressed over time experiencing decline in global cognition (b = -0.04, p < 0.001), attention (b = -0.05, p < 0.001) and executive function (b = -0.05, p < 0.001), compared to the non-depressed group. Our findings suggest that depression in later life may not precede cognitive decline. Instead, depressive symptoms and cognitive decline, particularly in attention and executive function, may evolve in tandem over time. This reinforces the importance of early identification and treatment of depression in older adults to potentially mitigate cognitive deterioration.

Unlocking the full potential of resistance training: a comparative analysis of low- and high-intensity effects on neurotrophic growth factors and homocysteine

ObjectiveResistance training has been demonstrated an effective approach for preventing the cognitive function decline through physiological mechanisms; however, the effect of acute resistance training at different intensities on growth factor and homocysteine levels remains unclear. This study aimed to compare the impact of resistance training at varying intensities on peripheral neurobiological factors and homocysteine levels in young adults.MethodsTwelve young male adults, predominantly engaged in various sports activities but without prior strength training experience, were recruited to participate in a randomized controlled cross-over trial. They implemented two different resistance training protocols: high intensity (HIRT, 12 repetitions at 80% 1RM) and low intensity (LIRT, 24 repetitions at 40% 1RM). Blood samples were collected at three time points: pre-training, post training, and after 30 min of rest to measure changes in serum lactate, serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), irisin, and plasma homocysteine (Hcy) levels.ResultsBoth resistance training protocols significantly increased blood lactate and perceived exertion compared to pre-training (HIRT, p < 0.01; LIRT, p < 0.01), with higher levels observed in HIRT. Acute HIRT significantly elevated serum BDNF, IGF-1, and VEGF levels post training compared to LIRT (p < 0.05), while no difference was observed in irisin levels between the two protocols at any time point. Both training protocols significantly reduced plasma Hcy levels post training (p < 0.01) and maintained lower levels than pre-training and after 30 min of rest (p < 0.05), with no significant differences between the two protocols.ConclusionsThis study demonstrates that high intensity training appears to have a greater impact on specific neurobiological factors; however, regardless of intensity, resistance training can significantly decrease plasma homocysteine.Trial registration ClinicalTrials.gov ID: NCT06114550. Date of registration 01/30/2024. https://clinicaltrials.gov/study/NCT06114550.

Melatonin Overexpression in the Management of Alzheimer's Disease: Therapeutic Exploration.

Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is characterized by the accumulation of neurofibrillary tangles and β-amyloid plaques, leading to a decline in cognitive function. AD is characterized by tau protein hyperphosphorylation and extracellular β-amyloid accumulation. Even after much research, there are still no proven cures for AD. The neuroprotective, anti-inflammatory, and antioxidant qualities of melatonin, a hormone mostly produced by the pineal gland, have drawn interest as a possible treatment option for AD. This study looks at new evidence that suggests melatonin overexpression to be a promising therapy option for AD. Melatonin levels naturally decline with age and decrease more significantly in individuals with AD, worsening neurodegenerative processes. Melatonin has therapeutic potential as it inhibits Aβ formation, prevents amyloid fibril extension through structure-dependent interactions, and protects neurons from Aβ-induced toxicity. Melatonin promotes neurogenesis, which is decreased in AD, suggesting it may treat the disease's many pathologies. The review emphasizes the importance of melatonin's mechanisms of action, including its capacity to reduce neuroinflammation, regulate mitochondrial function, scavenge free radicals, and influence apoptotic pathways. As research into AD continues, this article provides a forward-looking perspective on how future studies could leverage melatonin's multifaceted neuroprotective properties to develop more effective treatments for AD.

Research Progress in the Molecular Mechanism of NLRP3 Inflammasome in Alzheimer's Disease and Regulation by Natural Plant Products.

Alzheimer's disease (AD) is a prominent neurodegenerative disorder affecting the central nervous system in the elderly. Current understanding of AD primarily centers on the gradual decline in cognitive and memory functions, believed to be influenced by factors including mitochondrial dysfunction, β-amyloid aggregation, and neuroinflammation. Emerging research indicates that neuroinflammation plays a significant role in the development of AD, with the inflammasome potentially mediating inflammatory responses that contribute to neurodegeneration. Recent studies in AD pathology have identified a novel form of inflammasome referred to as NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Pathological alterations closely associated with NLRP3 inflammasome activation have been observed in the brain tissues of AD patients, transgenic mice, and in vitro neurocyte models. Numerous studies have demonstrated the potent neuroprotective properties of natural plant products (NPPs) against NLRP3 inflammasome-mediated AD pathology. This review provides a comprehensive examination of the NLRP3 inflammasome, its involvement in AD pathology, and the mechanisms underlying the therapeutic effects of NPP targeting the NLRP3 inflammasome.

Preliminary evidence of immune infiltration and neutrophil degranulation in peripheral blood of non-obese OSA patients related to cognitive decline

Obstructive sleep apnea (OSA) patients have varying degrees of cognitive impairment, but the specific pathogenic mechanism is still unclear. Meanwhile, poor compliance with continuous positive airway pressure (CPAP) in OSA prompts better solutions. This study aimed to identify differentially expressed genes between the non-obese OSA patients and healthy controls, and to explore potential biomarkers associated with cognitive impairment. Cohorts of healthy control (n = 20) and non-obese, treatment-naïve OSA patients (n = 20) were recruited. We collected their peripheral blood mononuclear cells and neutrophils, and their cognitive performances were evaluated by the Montreal Cognitive Assessment (MoCA). The differentially expressed genes were identified by bioinformatic analysis and confirmed by PCR. Imbalanced immune cell proportions were assessed by Cibersort. Biomarkers related to enriched cellular pathways were measured by ELISA. OSA patients showed a significant decline in overall cognitive function and were associated with higher daytime sleepiness scores. Multiple signaling pathways were enriched in the non-obese OSA cohort, including upregulation of neutrophil-degranulation. Increased monocyte proportion and decreased NK cell proportion were figured out. The relevant genes, including upregulated defensin alpha 4 (DEFA4), haptoglobin (HP), survivin (BIRC5), and suppressed interferon gamma (IFNG) expression were detected. The relative expression of DEFA4 was significantly correlated with the MoCA score and sleep parameters. Biomarkers such as myeloperoxidase (MPO), H2O2, and lipocalin-2, as representatives of neutrophils’ activation, elevated significantly in the OSA group. The data demonstrated a positive correlation between MPO and oxygen desaturation index (ODI) and a negative correlation between MPO and lowest oxygen saturation (LSaO2). The level of Lipocalin-2 was positively correlated with apnea-hypopnea index (AHI) and ODI and negatively correlated with LSaO2 and MoCA score. We also observed a negative correlation between H2O2 and mean oxygen saturation (MSaO2). Degranulation of neutrophils was activated in non-obese OSA patients without other complications. The process is related to OSA severity and cognitive impairment, implying its role in pathogenesis.

Evaluation of Cognitive Functions in People Living with HIV Before and After COVID-19 Infection.

Cognitive function decline is a problem in aging people living with HIV (PLWHIV). COVID-19 infection is associated with neuropsychiatric manifestations that may persist. The aim of our study was to evaluate cognitive function in PLWHIV before and after COVID-19 infection. This was a prospective observational study conducted at "Laiko" General Hospital from July 2019 to July 2024. The Montreal Cognitive Assessment (MOCA) scale was used to evaluate cognitive functions. 116 virally suppressed PLWHIV participated (mean age: 47.6 years, 91.4% male); 60 underwent repeated evaluation after the pandemic at a median interval of 3.1 years. The median MOCA score was 24 (22-26), with 35.3% scoring within normal limits. A negative correlation was observed between MOCA scores and age (ρ = -0.283, p = 0.002), but not with a CD4 count at diagnosis (ρ = 0.169, p = 0.071) or initial HIV RNA load (ρ = 0.02, p = 0.984). In the subgroup with repeated testing, MOCA was correlated with the CD4 count (ρ = 0.238, p = 0.069 in the first and ρ = 0.319, p = 0.014 second test). An improvement in performance was observed (median score increase from 24 to 25, p = 0.02). MOCA can detect early changes in cognitive function in PLWHIV. Further studies are required to determine the role of COVID-19 over time.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.5 years compared with 46 controls (false discovery rate (FDR) > 0.3). However, cerebrospinal fluid (CSF) markers showed very early signs of neurodegeneration in HDGE with elevated neurofilament light (NfL) protein, an indicator of neuroaxonal damage (FDR = 3.2 × 10-12), and reduced proenkephalin (PENK), a surrogate marker for the state of striatal medium spiny neurons (FDR = 2.6 × 10-3), accompanied by brain atrophy, predominantly in the caudate (FDR = 5.5 × 10-10) and putamen (FDR = 1.2 × 10-9). Longitudinal increase in somatic CAG repeat expansion ratio (SER) in blood was a significant predictor of subsequent caudate (FDR = 0.072) and putamen (FDR = 0.148) atrophy. Atypical loss of interruption HTT repeat structures, known to predict earlier age at clinical motor diagnosis, was associated with substantially faster caudate and putamen atrophy. We provide evidence in living humans that the influence of CAG length on HD neuropathology is mediated by somatic CAG repeat expansion. These critical mechanistic insights into the earliest neurodegenerative changes will inform the design of preventative clinical trials aimed at modulating somatic expansion. ClinicalTrials.gov registration: NCT06391619 .

Cognitive dysfunction, psychiatric distress, and functional decline after liver transplantation

Impaired cognition in liver recipients has been studied in the immediate post-transplant period but is poorly understood long-term, despite its importance to quality of life. In a single-center cohort of liver recipients transplanted 2010-2022 and &gt;1 years post-transplant, we assessed cognitive performance using a telephone-based battery. We compared depression, anxiety, and self-reported function by cognitive performance using descriptive statistics. Among 120 participants (median age 65, median 7.3 y post-transplant), 25% had below-expectation cognition, 53% at-expectation cognition, and 22% above-expectation. Baseline characteristics were similar between groups. Below-expectation performance was most commonly observed in verbal learning (28%) and verbal memory (22%). Overall, 46% had symptoms of depression (38%) and/or anxiety (28%); anxiety was less common among those with above-expectation cognition (0%) versus below-expectation (34%) or at-expectation cognition (38%, P=0.01). Impaired global daily function was reported by 36% of recipients but was not associated with objective cognitive performance. Below-expectation cognition was prevalent among 25% of liver recipients at least 1 year post-transplant and was associated with higher likelihood of reporting psychiatric distress. These findings underscore the need for longitudinal assessment of cognitive and mental health outcomes among liver transplant recipients.

MicroRNAs signatures as potential molecular markers in mild cognitive impairment: a meta-analysis.

Mild cognitive impairment (MCI) is characterized by a decline in cognitive functioning without significant interference in daily activities. Its high heterogeneity and elevated conversion rate to dementia pose challenges for accurate diagnosis and monitoring, highlighting the urgent need to identify methodologies focused on the early detection and intervention of MCI. Due to their biological characteristics, microRNAs (miRNAs) are potential candidates as non-invasive molecular markers for the identification and assessment of MCI progression. Therefore, in this study, we conducted a meta-analysis to identify the miRNAs commonly deregulated in MCI, focusing on expression profiles in plasma, serum, and extracellular vesicle samples. Our analysis identified eight upregulated miRNAs, including hsa-miR-149-3p, and four downregulated miRNAs, such as Let-7f-5p. Notably, hsa-miR-149-3p emerged as a central node in interaction networks, suggesting its crucial role in regulating cellular processes relevant to MCI. Additionally, pathway analysis revealed significant enrichment in biological processes associated with transcriptional regulation and neurodegeneration. Our results underscore the potential of circulating miRNAs as non-invasive molecular markers for MCI and open the possibility for new methodologies that enable more accurate diagnosis and monitoring of disease progression. Validating the expression of miRNAs such as hsa-miR-149-3p and Let-7f-5p, along with identifying their functional role in the specific context of MCI, is essential to establish their biological relevance. This work contributes to the understanding of the miRNA profile in mild cognitive impairment using easily accessible samples, which could be useful for the development of various strategies aimed at preventing or delaying MCI in individuals at risk of developing dementia, including Alzheimer's disease.

Phytomedicine Potential of Oroxylum indicum Root and Its Constituents: Targeting Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive function, for which few effective treatments exist. This study investigated the neuroprotective potential of Oroxylum indicum root extract and its key constituents (baicalein, chrysin, oroxylin A) against AD hallmarks. The extract and its constituents exhibited antioxidant activity in the DPPH assay. They inhibited β-amyloid aggregation as measured by the thioflavin T assay and acetylcholinesterase activity using the Ellman method. In cell culture models, O. indicum extract showed an ability to protect neurons from the toxic effects of H2O2. Western blot analysis revealed the extract and its major active component, baicalein, downregulated pro-apoptotic markers (cleaved caspase-3, and BAX) upon H2O2 exposure. Furthermore, they reduced the expression of amyloidogenic proteins (BACE1) and phosphorylated tau. These findings suggest that O. indicum root extract, particularly baicalein, possesses multifaceted neuroprotective properties, targeting various aspects of AD pathogenesis, including oxidative stress, cholinergic dysfunction, β-amyloid formation, aggregation, and apoptosis. O. indicum root thus warrants further investigation as a promising source of therapeutic agents for AD.

Mechanistic insight into neuroprotective effect of standardized ginger chemo varieties from Manipur, India in scopolamine induced learning and memory impaired mice.

Alzheimer's disease is a complex neurodegenerative disease characterized by progressive decline in cognitive function and behaviour. Ginger is the rhizome of the plant Zingiber officinale Roscoe, has been an important ingredient of many Ayurveda formulations to treat neurological disorders. The present study aims to estimate the variation of 6-gingerol content in nine different ginger samples collected from Manipur, India, investigate the neuroprotective potential of the most potent ginger sample against scopolamine-induced cognitively impaired mice, and validate the therapeutic claim by molecular docking analysis. High Performance Thin Layer Chromatography (HPTLC) analysis suggested that the sample GV6 had the highest 6-gingerol content with potent in vitro acetylcholnesterase (AChE) (IC50 = 336.10µg/mL) and butyrylcholinesterase (BChE) (IC50 = 411.73µg/mL) enzyme inhibitory activity. The neuroprotective potential of GV6 was tested in scopolamine-induced cognitively impaired mice (200 and 400mg/kg). The behavioral analysis showed that GV6 alleviated the spatial recognition, and short-term and long-term memory in the experimental mice model. GV6 significantly improved brain AChE and BChE activity, acetylcholine (ACh) level, markedly alleviated the antioxidant parameters, and reversed the neuroinflammation. Brain histopathological observations confirmed the presence of organized nerve fibers, improvement of neuronal cell density, and reverse the nucleus shrinkage. Further molecular docking analysis showed that 6-gingerol and galantamine exhibited stable interaction with AChE (-7.5 and - 7.3 kcaL/moL) and BChE (-7.3 and - 8.5 kcaL/moL). The present study emphasizes the quality-related therapeutic importance of ginger samples from Northeast India and demonstrates that administration of GV6 may improve brain cognitive functions by restoring neurotransmitter levels and inflammatory and antioxidant parameters in scopolamine-induced cognitively impaired mice.

Determining Clinical Disease Progression in Symptomatic Patients With CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent small artery brain disease caused by pathogenic variants of the NOTCH3 gene. During the disease, we still do not know how the various deficits progress and develop with each other at different stages of the disease. We aim to model disease progression and identify possible progressive subgroups and the effects of different covariates on clinical worsening. Data were obtained from patients followed in the French CADASIL referral center, who were aged 25-80 years and had completed at least 2 visits and one of 14 clinical scores. Progression and variability were assessed using a disease course model (Leaspy). A Gaussian mixture model was used to identify different progression subgroups. Logistic regressions were used to compare the characteristics between groups. In 395 patients along 2,007 visits, the follow-up ranged from 6 months to 19 years, with a mean of 7.5 years. They were 45% men with a mean age of 52.2 years. The evolution curves of the different scores showed that clinical manifestations develop heterogeneously and can vary considerably depending on the disease stage. We identified an early-onset, rapidly progressing subgroup of patients with earlier motor symptoms and focal neurologic deficits (median time shift 59 [Q1-Q3 48.9-66.3], median acceleration rate 0.84 [0.07-1.31]) and a late-onset slowly progressing group with earlier cognitive symptoms (median time shift 69.2 [63.4-75.1], median acceleration rate -0.18 [-0.48 to 0.14]). Male sex, lower education level, hypertension, and NOTCH3 pathogenic variant location within epidermal growth factor-like repeat (EGFr) 1-6 were found to be associated with this group difference. Our results suggest a gradual and heterogeneous decline in different clinical and cognitive performances over the lifetime of patients with CADASIL. Two progression profiles-one rapid and early and the other, more delayed and slower-are possible after the onset of symptoms. A major limitation of our study is that the clusters were assessed post hoc, which may induce some bias. Overall, male sex, low level of education, pathogenic variant location in EGFr 1 to 6 domains, smoking, and/or arterial hypertension may affect the clinical progression of the disease.

Effect of serum uric acid to creatinine ratio on cognitive function decline in middle-aged adults: Longitudinal evidence from CHARLS.

Serum uric acid (SUA) was a predictor of cognitive function. The association of SUA/serum creatinine ratio (Scr), which represents renal function-normalized SUA and cognitive function is unknown. This study investigated the association of the SUA/Scr with cognitive function and the potential mediation effect of inflammation in the above relationship. This study used 1-5 waves of data from the China Health and Retirement Longitudinal Study. 3302 participants aged 45-60 years at baseline were included. Among them, 1129 who attended subsequent 2-3 waves were further included for cumulative exposure calculation to the SUA/Scr ratio. The Cox models were used to evaluate the impact of baseline SUA/Scr ratio and its cumulative exposure on cognitive function decline. During a median follow-up of 8.6 years, there were 1512 (45.8%) cognitive function declined. After adjustment, the highest quartile of the SUA/SCr ratio was associated with the highest risk of cognitive function decline (Hazard ratio, 1.175; 95% confidence interval, 1.015-1.360). Restricted cubic spline showed a linear association between the SUA/Scr ratio and the risk of cognitive function decline (pnon-linear = 0.514). There were a stronger association of cumulative SUA/Scr ratio and its exposure burden with cognitive function decline [the highest versus lowest quartile: 1.635 (1.006-2.656), the high versus low group: 1.729 (1.212-2.466), respectively]. No significant mediating effect through white blood cell count or C-reactive protein in SUA/Scr ratio-cognitive function decline was found. The SUA/Scr ratio was associated with a higher risk of cognitive decline, whereas the mechanism mediated by inflammation indicators was not found.

Long-term Cognitive Trajectories in Older Adults After Surgery: A Population-based Cohort Study.

Postoperative cognitive decline (POCD) is a common, but often unrecognized condition after surgery. We evaluate postsurgical cognitive changes in a longitudinal population-based study. The study cohort comprises an age-stratified population-based random sample of individuals aged 65+ years from a small-town region of the United States. We identified as cases those participants who, during annual assessments, self-reported having undergone surgery under general anesthesia during the preceding year. We identified as controls those who reported no surgery for at least 6 consecutive years. The outcome variable changed over time (4y) in annual cognitive test composite scores encompassing the domains of attention/processing speed, executive function, memory, language, and visuospatial functions, which were modeled using Generalized Estimating Equations. A total of 436 participants had the required cognitive data; 179 participants (cases) had undergone surgery, while 257 participants (controls) had not undergone surgery. After adjusting for age, years of education, gender, race, heart failure, irregular heartbeat, and stroke, participants who underwent surgery had a greater decline in executive function, memory, and attention over a 2-year period. Participants who underwent surgery had a significant subsequent decline in cognitive function over the long term.

The Impact of the COVID-19 Pandemic on Oldest-Old Social Capital and Health and the Role of Digital Inequalities: Longitudinal Cohort Study.

During the COVID-19 pandemic, information and communication technology (ICT) became crucial for staying connected with loved ones and accessing health services. In this scenario, disparities in ICT use may have exacerbated other forms of inequality, especially among older adults who were less familiar with technology and more vulnerable to severe COVID-19 health consequences. This study investigated changes in ICT use, psychological and physical health, and social capital before and after the pandemic among the oldest old population (aged 80 years or older after the pandemic) and explored how internet use influenced these changes. We leveraged data from the InveCe.Ab study, a population-based longitudinal cohort of people born between 1935 and 1939 and living in Abbiategrasso, a municipality on the outskirts of Milan, Italy. Participants underwent multidimensional assessment at baseline (2010) and after 2, 4, 8, and 12 years. We restricted our analysis to cohort members who participated in the last wave (ie, 2022) and who did not have a diagnosis of dementia (n=391). We used linear mixed models to assess the impact of COVID-19 and time on changes in social capital, physical and psychological health, and ICT use in a discontinuity regression design while controlling for age, sex, education, and income satisfaction. Then, we assessed the influence of internet use and its interaction with COVID-19 on these changes. COVID-19 had a significant impact on social relationships (β=-4.35, 95% CI 6.38 to -2.32; P<.001), cultural activities (β=-.55, 95% CI -0.75 to -0.35; P<.001), cognitive functioning (β=-1.00, 95% CI -1.28 to -0.72; P<.001), depressive symptoms (β=.42, 95% CI 0.10-0.74; P=.009), physical health (β=.07, 95% CI 0.04-0.10; P<.001), and ICT use (β=-.11, 95% CI -0.18 to -0.03; P=.008). Internet use predicts reduced depressive symptoms (β=-.56, 95% CI -1.07 to -0.06; P=.03) over time. The interaction between internet use and COVID-19 was significant for cultural activities (β=-.73, 95% CI -1.22 to -0.24; P=.003) and cognitive functioning (β=1.36, 95% CI 0.67-2.05; P<.001). The pandemic had adverse effects on older adults' health and social capital. Contrary to expectations, even ICT use dropped significantly after the pandemic. Internet users maintained higher psychological health regardless of time and COVID-19 status. However, COVID-19 was associated with a steeper decline in cognitive functioning among internet nonusers. Policy makers may develop initiatives to encourage ICT adoption among older adults or strengthen their digital skills. ClinicalTrials.gov NCT01345110; https://clinicaltrials.gov/study/NCT01345110.

Effect of Hyaluronan Molecular Weight on the Stability and Biofunctionality of Microfibers Assembled by Interfacial Polyelectrolyte Complexation.

Nervous system disorders are characterized by a progressive loss of function and structure of neurons that ultimately leads to a decline in cognitive and motor functions. In this study, we used interfacial polyelectrolyte complexation (IPC) to produce fibers for neural tissue regeneration. IPC is a processing method that allows spinning of sensitive biopolymers. The rate of spinning and the properties of the used biopolymers (charge and molecular weight) influence different characteristics of the fibers such as size and stability, among others. We used two major components of the neuronal stem cell niche, the polycationic collagen (Col) and the polyanionic hyaluronic acid (HA), to obtain bioactive fibers. We tested HA with different molecular weights and found that HA with medium and high molecular weights (350 and 1200 kDa, respectively) enabled drawing of microfibers with a homogeneous distribution of Col and HA, whereas low-molecular-weight HA (40 kDa) did not allow spinning. The obtained microfibers showed high swelling ability in a physiological buffer: their diameters increased more than 5-fold from their dry state. At these conditions, the tensile storage moduli of the fibers were similar to nervous tissues. Collagenase and hyaluronidase did not change the morphology of the fibers for up to 3 days but reduced their moduli 2- to 3-fold. Assays with PC12 neuronal-like cells showed that IPC microfibers support cell adhesion and viability regardless of the molecular weight of the used HA.