Mini-Mental State Examination Score Research Articles

Plasma Biomarkers Predict Cognitive Decline in Alzheimer's Disease

AbstractBackgroundAlzheimer's disease (AD) features a complex interplay of factors influencing cognitive decline. While CSF and plasma biomarkers have widely demonstrated their diagnostic utility, whether they may add prognostic value remains unrevealed. With this longitudinal study we aim to address this knowledge gap by evaluating the predictive value of several fluid biomarkers over cognitive decline in a cohort of biomarker‐confirmed AD individuals.MethodWe included 139 participants with biologically‐confirmed AD (A+T+N+). Four cerebrospinal fluid (CSF) biomarkers (Amyloid‐Beta1‐42 [Aβ1‐42], tau phosphorylated at threonine 181 [p‐tau181], total tau [t‐tau], and neurofilament light chain [NfL]) were determined with enzyme immunoassay, and three plasma biomarkers (p‐tau181, NfL and glial fibrillary acidic protein [GFAP]) were determined with single‐molecule array. Biomarkers were stratified into tertiles. Comprehensive neuropsychological assessments were administered at baseline (n=139) and annually (Year 1 n=108, Year 2 n=78, Year 3 n=25, Year 4 n=3 and Year 5 n=3; mean follow‐up time 1.7 years [SD 0.3]). Mixed Models for Repeated Measures explored the effectof CSF and blood biomarkers on Mini‐Mental State Examination (MMSE) score progression.ResultParticipants had a mean age at onset of 65.7 (SD 6.4) years, 17% were non‐amnestic, 58% were APOEε4 carriers. Higher baseline plasma p‐tau181 and GFAP concentrations correlated with MMSE score decline (p=0.009 and p=0.002, respectively) (Table 1, Table 2, Figure 1). Conversely, no significant associations were observed between plasma NfL or CSF biomarkers concentrations and MMSE decline.ConclusionThis longitudinal study highlights the potential prognostic value of baseline plasma p‐tau181 and GFAP concentrations for cognitive decline progression in AD.

Associations among Neurofilament light chain (NfL), Depressive Symptoms and Cognition in autosomal dominant Alzheimer´s disease

AbstractBackgroundDepressive symptoms are associated with neurodegeneration in individuals at increased risk for late‐onset Alzheimer’s disease, but these relationships are less clear in younger individuals and those at risk for autosomal dominant Alzheimer’s Disease (ADAD). Neurofilament light chain (NfL) is a biomarker of axonal damage and neuronal degeneration that becomes abnormal several decades before clinical onset in ADAD. To address this gap, we investigated the associations among depressive symptoms, plasma NfL and cognition in a younger cohort affected by the PSEN1‐E280A genetic variant. Carriers of this variant usually develop dementia by their 50s.MethodA total of 677 carriers (574 cognitively unimpaired and 103 cognitively impaired) and 620 non‐carriers (median age 32 [Interquartile range IQR 24‐42], 55% women, 8 median education years [IQR 4‐11] from the Colombian kindred with ADAD due to the PSEN1‐E280A mutation were included. Participants underwent a neuropsychological evaluation, which included the Mini‐Mental State Examination (MMSE), a Spanish version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list learning test (WLL), the 15‐item Geriatric Depression Scale (GDS), and the Functional Assessment Staging Test (FAST) to assess functional independence. Mann‐Whitney‐Wilcoxon test was used to examine group differences, and Spearman’s correlations were used to investigate associations among depressive symptoms, NfL and cognition.ResultCompared to non‐carriers, carriers had higher levels of NfL (carriers=10.98, IQR 5.34‐13.44; non‐carriers=7.41, IQR 4.68‐8.90, p<0.001). There were no group differences in depressive symptoms (carriers =3.44, IQR 1‐5; non‐carriers=2.73, IQR 1‐4, p=0.19). In carriers, higher NfL levels were associated with higher GDS scores (r=0.093; p<0.001). Higher GDS scores were associated with lower MMSE scores (r= ‐0.18; p<0.001) and poorer CERAD WLL performance (r=‐0.17; p<0.001).ConclusionOur study showed that higher NfL plasma levels are associated with higher levels of self‐reported depressive symptoms in individuals with ADAD. These findings support neurodegenerative pathology underlying neuropsychiatric symptoms in ADAD and that these relationships can be detected using plasma measures. Future longitudinal analyses, examining other pathological mechanisms, and GDS‐items are needed to understand these symptoms more clearly in individuals with ADAD and whether they may be useful targets for AD prevention efforts.

The anticholinergic burden in patients with chronic kidney disease: Patterns, risk factors, and the link with cognitive impairment.

People with chronic kidney disease (CKD) have an elevated risk of cognitive impairment (CI). Medications with anticholinergic activity are recognized for their adverse reactions on central nervous system. The putative association between the anticholinergic burden and CI has not previously been evaluated in patients with CKD. The study aimed to (i) describe prescriptions of medications with anticholinergic activity, (ii) analyze factors associated with these prescriptions, and (iii) evaluate the anticholinergic burden's association with cognitive performance. CKD-REIN, a prospective cohort study, enrolled nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 mL/min/1.73m2). Drug prescriptions were recorded prospectively during the 5-year follow-up. Mini Mental State Examination (MMSE) was assessed at baseline and CI was defined as an MMSE score <24/30. For each patient, the anticholinergic burden was determined by summing the Anticholinergic Cognitive Burden (ACB) scores of all prescription drugs at baseline. Multinomial logistic regression was used to analyze factors associated with the ACB score. Logistic regression was used to evaluate the association between the cognitive impairment and the anticholinergic burden at baseline. At baseline, 3007 patients (median age [IQR], 69[60-76]; 65% men) had MMSE data and were included. 1549 (52%) of these patients were taking at least one drug with anticholinergic properties. Most (1092; 70%) had a low anticholinergic burden, 294 (19%) had a moderate anticholinergic burden, and 163 (11%) had a high anticholinergic burden. A history of neurological/psychiatric disorders and a higher number of daily drugs were associated with a greater probability of having a high anticholinergic burden (odds ratio (OR) [95% confidence interval (95% CI)] = 1.88[1.29;2.74] and 1.53[1.45;1.61], respectively). Patients with a high anticholinergic burden had a significantly higher probability of presenting cognitive impairment, compared with patients without an anticholinergic burden (OR[95% CI] = 1.76[1.12;2.75]) after adjustment for sociodemographic factors, comorbidities, laboratory data, and the number of medications taken daily. The results of our study emphasize the need for caution in the prescription of drugs with anticholinergic properties to patients with CKD.

Inhibition of zDHHC7-driven protein S-palmitoylation prevents cognitive deficits in an experimental model of Alzheimer’s disease

Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein S-palmitoylation in hippocampi of both 3×Tg-AD mice and post-mortem Alzheimer's disease (AD) patients. Chronic intranasal administration of the S-palmitoylation inhibitor 2-bromopalmitate counteracted synaptic plasticity and cognitive deficits, reduced the Aβ deposition in the hippocampus and extended the lifespan of both male and female 3×Tg-AD mice. Moreover, hippocampal silencing of zDHHC7 prevented the onset of cognitive deficits in the same experimental model. We also identified a FoxO1-mediated epigenetic mechanism inducing zDHHC7 expression, which was triggered by brain insulin resistance in 3×Tg-AD mice. Finally, in hippocampi of AD patients S-palmitoylation levels of Beta-Secretase 1 were associated with Aβ 1 to 42 load and they inversely correlated with Mini Mental State Examination scores. Our data reveal a key role of both zDHHC7 overexpression and protein hyperpalmitoylation in the onset and progression of AD-related alterations of synaptic plasticity and memory.

Thyroid Functions and Cognitive Decline in the Elderly.

Background The maintenance of cognitive health depends on thyroid hormones, and it is becoming more widely acknowledged that thyroid hormoneissues may be a factor in cognitive decline in the aged. Objective This study aimed to investigate the association between thyroid hormone levels and cognitive decline among elderly individuals, considering the influence of age-related factors and comorbidities. Methodology Over the course of two years, 218 adults 60 years of age and older with clinically diagnosed hypothyroidism or subclinical thyroid disease were included in a prospective observational research. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (T4), and free triiodothyronine (T3) were measured at baseline and at 6, 12, 18, and 24-month intervals to evaluate thyroid function. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were used to assess cognitive function at the same intervals. Factors linked to cognitive deterioration were identified using multivariate regression analysis. Results The study found that TSH levels decreased from 3.20 ± 1.82 µIU/mL at baseline to 2.80 ± 1.51 by 24 months (p < 0.001), while free T4 levels increased from 13.50 ± 2.53 pmol/L to 14.20 ± 2.52 pmol/L (p = 0.020). Cognitive scores declined significantly, with MMSE scores dropping from 23.27 ± 4.64 to 21.80 ± 4.89 (p = 0.005) and MoCA scores from 21.20 ± 5.11 to 20.03 ± 5.51 (p = 0.012). Conclusion The results show a strong correlation between thyroid malfunction and cognitive loss in the elderly, emphasizing the need to closely monitor thyroid function to maintain cognitive function in this population.

Application Of Reminiscence Therapy As An Improving Effort Cognitive Function Of Older Age

Cognitive decline in the elderly can affect their physical abilities and quality of life. Cognitive decline is often characterized by impaired memory and communication, resulting in dependence on others. This study aims to apply reminiscence therapy as an effort to improve cognitive function in the elderly. The case study was conducted using the gerontic nursing care process approach. The research subjects consisted of two elderly over 60 years old with cognitive impairment, who were evaluated using the Mini Mental State Examination (MMSE). Reminiscence therapy was implemented in 3 sessions for 2 weeks, each lasting 90 minutes. After the application of reminiscence therapy, both subjects' MMSE scores improved. The first subject showed the score increased from 15 to 21, while the second subject from 16 to 23, which showed improvement in the category of cognitive impairment. The application of reminiscence therapy is able to stimulate long-term memory and improve cognitive function in the elderly. These results are in line with previous research which shows that this therapy is effective in improving cognitive abilities and quality of life of the elderly. Reminiscence therapy is an important intervention to improve memory and cognitive function in the elderly with cognitive impairment. The application of this therapy can make a significant contribution to the care of the elderly and improve their quality of life.

Different oscillatory mechanisms of dementia-related diseases with cognitive impairment in closed-eye state

The escalating global trend of aging has intensified the focus on health concerns prevalent among the elderly. Notably, Dementia related diseases, including Alzheimer's disease (AD) and frontotemporal dementia (FTD), significantly impair the quality of life for both affected seniors and their caregivers. However, the underlying neural mechanisms of these diseases remain incompletely understood, especially in terms of neural oscillations. In this study, we leveraged an open dataset containing 36 CE, 23 FTD, and 29 healthy controls (HC) to investigate these mechanisms. We accurately and clearly identified three stable oscillation targets (theta, ∼5 Hz, alpha, ∼10 Hz, and beta, ∼18 Hz) that facilitate differentiation between AD, FTD, and HC both statistically and through classification using machine learning algorithms. Overall, the differences between AD and HC were the most pronounced, with FTD exhibiting intermediate characteristics. The differences in the theta and alpha bands showed a global pattern, whereas the differences in the beta band were localized to the central-temporal region. Moreover, our analysis revealed that the relative theta power was significantly and negatively correlated with the Mini Mental State Examination (MMSE) scores, while the relative alpha and beta power showed a significant positive correlation. This study is the first to pinpoint multiple robust and effective neural oscillation targets to distinguish AD, offering a simple and convenient method that holds promise for future applications in the early screening of large-scale dementia-related diseases.

A diffusion kurtosis imaging study of the relationship between whole brain microstructure and cognitive function in older adults with mild cognitive impairment.

The association of Mini-Mental State Examination (MMSE) with microstructure of individual regions across the entire brain remains unexplored. To investigate the relationship between cognitive function and the microstructure of each brain region in the gray matter using diffusion kurtosis imaging (DKI) in older adults with mild cognitive impairment (MCI), which is the transitional stage before the onset of dementia. DKI and MMSE were obtained for 34 older adults with MCI and 16 cognitively normal (CN) individuals aged 65-85 years. The DKI parameters were measured from 31 distinct regions of interest in the gray matter. A multiple regression analysis was used to examine the association between DKI parameters and MMSE scores; subsequently, interactions between the DKI parameters and the groups (MCI and CN) were examined. The mean (±SD) MMSE score for the MCI group was 27.67 ± 1.90. Significant positive correlations were observed between MMSE score and mean kurtosis (MK) in the superior frontal, middle frontal, inferior frontal, precentral, postcentral, angular, middle temporal, and inferior occipital gyri, and superior parietal lobe for the MCI group. In addition, the interaction term of the MK in the middle frontal, precentral, postcentral, and angular gyri, and the groups was statistically significant. Older adults with MCI may exhibit histological damage in certain regions of the brain, such as the middle frontal and angular gyri, as observed in this study. The findings could provide insights into understanding the pathophysiology of cognitive decline in this population group.

A randomized clinical trial evaluating Hydralazine’s efficacy in early-stage Alzheimer’s disease: The EHSAN Study

Alzheimer’s Disease (AD), a neurodegenerative disorder escalating worldwide, remains incurable with existing interventions merely mitigating symptoms. Hydralazine, an antihypertensive agent, has displayed neuroprotective potential in AD animal models via amplification of mitochondrial functionality and stimulation of stress management and repair pathways. Nevertheless, its effectiveness and tolerability in human AD cohorts are yet to be confirmed. This study protocol describes the design of an ongoing, single-center, randomized, triple-blind, placebo-controlled trial to assess hydralazine’s effects on cognitive function in mild to moderate -stage AD patients. We will enroll 424 patients aged 50 and older, meeting NINCDS-ADRDA criteria for probable AD with Mini-Mental State Examination scores from 12–26. They’ll be randomly assigned to receive either hydralazine HCL (25 mg, thrice daily) or a placebo for 12 months. The primary outcome is the Alzheimer’s Disease Assessment Scale change from baseline to 12 months. Secondary outcomes include various measures using Lawton instrumental activities of daily living scale, neuropsychiatry inventory, and caregiver activity survey. This trial will explore the potential benefits and risks of hydralazine in mild to moderate AD treatment. It’s the first trial examining hydralazine’s impact on mild to moderate -stage AD in human and is registered at the Iranian Registry of Clinical Trials (IRCT20200711048075N1, registered 29/07/2020) and ClinicalTrials.gov (NCT 04,842,552AQ, registered 13/04/2021). Ethics approval was granted by the Research Ethics Committee of the National Institute for Medical Research Development (IR.NIMAD.REC.1398.424), following the SPIRIT Statement guidelines. Findings will be disseminated via peer-reviewed publications and conferences. This inaugural human clinical trial evaluates hydralazine’s impact on patients in the mild to moderate AD. Executed with a randomized, triple-blind, placebo-controlled methodology, this study incorporates a significant sample size and an extended monitoring duration. Multiple parameters, including cognitive capabilities, will be assessed. Potential limitations include the inherent homogeneity of the AD cohort, the lack of biomarker assays, and the unpredictable progression of the disease. Notably, the study might not elucidate the protracted effects of hydralazine beyond a 12-month period. Another limitation of our clinical trial is that patients were diagnosed with Alzheimer’s disease based solely on clinical evaluation and MRI findings, without the inclusion of specific biomarkers, which may impact the accuracy and specificity of the diagnosis. Trial registration: Iranian Registry of Clinical Trials (IRCT20200711048075N1, registered 29/07/2020) and ClinicalTrials.gov (NCT 04,842,552, registered 13/04/2021).

Evolution of Cognitive Disorders in Patients with Mild Cognitive Impairment (MCI) After Ischemic Stroke: Secondary Data Analysis from the Improved Health Care in Neurology and Psychiatry-Longer Life (IHCNP) Study.

The Improved Health Care in Neurology and Psychiatry-Longer Life (IHCNP) study was an 18-month prospective, observational, non-interventional research study focused on patients with mild cognitive impairment (MCI) following ischemic stroke. Our secondary analysis of the IHCNP data aimed to document the progression of MCI in this patient group. A total of 100 patients from Romania were recruited, all of whom underwent cognitive assessments using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Rey Auditory Verbal Learning Test (RAVLT). Clinical evaluations were also conducted as part of the study. Baseline cognitive scores were recorded, and subsequent follow-ups documented cognitive changes over time. At baseline, cognitive scores indicated mild impairment, with averages of MMSE 25.41, MoCA 23.27, and RAVLT 33.63. By the end of the study, patients exhibited a significant cognitive decline, with MMSE scores dropping by 8.7%, MoCA by 10.0%, and RAVLT by 29.5% (p < 0.0001 for all measures), reflecting the progressive nature of MCI post-stroke. These findings highlight the importance of early diagnosis and intervention to mitigate cognitive decline in post-stroke patients. The study underscores the need for ongoing cognitive monitoring to improve patient outcomes and manage MCI progression effectively.

Factors Influencing Poststroke Cognitive Dysfunction: Cross-Sectional Analysis.

Poststroke cognitive impairment (PSCI) is a common and debilitating complication that affects stroke survivors, impacting memory, attention, and executive function. Despite its prevalence, the factors contributing to PSCI remain unclear, with limited insights into how demographic and clinical variables influence cognitive outcomes. This study investigates the incidence of cognitive impairment in patients with stroke and examines key demographic and clinical factors, such as age, gender, and education level, which contribute to cognitive decline. The aim is to provide a deeper understanding of PSCI to inform early intervention strategies for improving patient outcomes. A cross-sectional study was conducted on 305 patients with ischemic stroke admitted to Zhongda Hospital, Southeast University, from January 2019 to September 2022. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) within 72 hours of hospital admission. Demographic information, including age, gender, and education level, were collected. Statistical analyses were performed using chi-square tests, independent t tests, and multivariate regression to assess the relationship between cognitive function and key variables. Pearson correlation analysis explored associations among age, education, and MMSE scores. Among the 305 patients with stroke, 16.7% (n=51) were diagnosed with cognitive impairment based on MMSE scores. The prevalence of cognitive impairment was slightly higher in males (17.6%, n=159) than females (15.8%, n=146), but this difference was not statistically significant. A strong negative correlation was found between MMSE scores and age (r=-0.32; P<.01), indicating that older patients had lower cognitive function. Education level showed a positive correlation with MMSE scores (r=0.41; P<.01), with patients with higher educational attainment demonstrating better cognitive outcomes. Cognitive function showed a marked decline in patients older than 60 years, particularly in domains such as memory, attention, and language skills. This study confirms that age and education are significant factors in determining cognitive outcomes after stroke. The results align with existing literature showing that cognitive function declines with age, while higher educational attainment serves as a protective factor. The findings suggest that individuals with greater cognitive reserve, often linked to higher education, are better equipped to cope with the impact of brain injury. However, the study's reliance on MMSE may have limited its ability to detect domain-specific impairments. Future studies should consider using more sensitive cognitive tools, such as the Montreal Cognitive Assessment (MoCA), to provide a more comprehensive evaluation of PSCI. Cognitive impairment is prevalent among stroke survivors, with age and education level being key factors influencing outcomes. These findings underscore the importance of early detection and targeted interventions to mitigate cognitive decline. Further research with larger samples and more sensitive cognitive assessments is needed to fully understand PSCI and improve rehabilitation strategies for patients with stroke.

Effectiveness of Repetitive Transcranial Magnetic Stimulation in Mild Cognitive Impairment and Early Alzheimer’s Disease: A Systematic Review and Meta-analysis

Background: Dementia encompasses cognitive decline that significantly affects daily living. In recent years, there has been a notable shift toward nonpharmacological treatments, with transcranial magnetic stimulation (TMS) gaining attraction for its potential to enhance cognitive function in predementia and early Alzheimer’s Disease (AD). In this meta-analysis, we have integrated the results from different studies with varied protocols to explore the efficacy of repetitive TMS (rTMS) in improving cognitive functioning in people with mild cognitive impairment (MCI) and early AD. Methods: We used three databases, namely PubMed, MEDLINE, and PsycINFO. Studies until March 2024 were included. Mini–Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) were used to assess global cognition. A random-effects meta-analytical model was adopted, and Hedge’s g standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were reported. The study protocol has been registered with PROSPERO (CRD42024507575). Results: Twenty-three studies were included in the meta-analysis. The mean (standard deviation) age of participants in studies using ADAS-Cog (71.8 [6.19] years) was found to be more than studies using MMSE (70.0 [6.72] years). Post-intervention MMSE scores were significantly better in active rTMS as compared to that of sham TMS (SMD [95% CI] =0.60 [0.15–1.04]; P = 0.009). However, the difference between the two study groups was not statistically significant for ADAS-Cog (−0.09 [−0.49 to 0.32]; [P = 0.67]). Sensitivity analyses for studies using MMSE also indicated that rTMS contributed to cognitive enhancement. Conclusions: The study found that active rTMS led to significant improvement in MMSE scores in people with MCI and early AD.

Temporal atrophy together with verbal encoding impairment is highly predictive for cognitive decline in typical Alzheimer's dementia - a retrospective follow-up study.

The increasing prevalence of Alzheimer's disease (AD) has created an urgent need for rapid and cost-effective methods to diagnose and monitor people at all stages of the disease. Progressive memory impairment and hippocampal atrophy are key features of the most common so-called typical variant of AD. However, studies evaluating detailed cognitive measures combined with region of interest (ROI)-based imaging markers of progression over the long term in the AD dementia (ADD) stage are rare. We conducted a retrospective longitudinal follow-up study in patients with mild to moderate ADD (aged 60-92 years). They underwent magnetic resonance imaging (MRI; 3 Tesla, MPRAGE) as well as clinical and neuropsychological examination (Consortium to Establish a Registry for Alzheimer's Disease [CERAD] -Plus test battery) at baseline and at least one follow-up visit. ROI-based brain structural analysis of baseline MRIs was performed using the Computational Anatomy Toolbox (CAT) 12. Clinical dementia progression (progression index [PI]) was measured by the annual decline in the Mini Mental State Examination (MMSE) scores. MRI, demographic, and neuropsychological data were included in univariate and multiple linear regression models to predict the PI. 104 ADD patients (age 63 to 90 years, 73% female, mean MMSE score 22.63 ± 3.77, mean follow-up 4.27 ± 2.15 years) and 32 age- and gender-matched cognitively intact controls were included. The pattern of gray matter (GM) atrophy and the cognitive profile were consistent with the amnestic/typical variant of ADD in all patients. Deficits in word list learning together with temporal lobe GM atrophy had the highest predictive value for rapid cognitive decline in the multiple linear regression model, accounting for 25.4% of the PI variance. Our results show that temporal atrophy together with deficits in the encoding of verbal material, rather than in immediate or delayed recall, is highly predictive for rapid cognitive decline in patients with mild to moderate amnestic/typical ADD. These findings point to the relevance of combining detailed cognitive and automated structural imaging analyses to predict clinical progression in patients with ADD.

Retinal vascular alterations are associated with cognitive function and neuroimaging in white matter hyperintensities

AimTo reveal alterations in retinal structure, vessels, and function, and their association with cognitive function and neuroimaging in white matter hyperintensities (WMH). MethodsThis study enlisted WMH and age-matched healthy controls (HC). All participants underwent six different tests: magnetic resonance imaging (MRI) of the brain, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), fundus photography, optical coherence tomography (OCT), and visual field testing. Visual field can reflect the function of optic nerve and retina. The peripapillary retinal nerve fiber layer (p-RNFL) was analyzed using OCT. Image J software was employed to measure retinal vascular caliber in fundus photographs and to compute the central retinal artery equivalent (CRAE), central retinal venous equivalent (CRVE) and arteriole-to-venule ratio (AVR). ResultsA total of 90 WMH patients and 93 HC participants. In comparison with the HC, the WMH group exhibited reduced cognitive function scores (MoCA: P < 0.001; MMSE: P < 0.001), narrower retinal arteries (P < 0.001), smaller AVR (P < 0.001) and thinner p-RNFL thickness (total: P = 0.026; temporal: P = 0.006). About visual field, both univariate and multivariate analysis showed that mean sensitivity decreased, and mean defect increased in WMH group (P < 0.05). Additionally, correlation analysis indicated a positive correlation between CRAE and AVR with MMSE and MoCA score (r = 0.424–0.57, P < 0.001) and a negative correlation with Fazekas score (CRAE: r = −0.515, P < 0.001; AVR: r = −0.554, P < 0.001), and p-RNFL was negatively correlated with Fazekas score (total p-RNFL: r = −0.192, P = 0.009; temporal p-RNFL: r = −0.217, P = 0.003). Notably, no significant correlation was found between cognitive function and p-RNFL. ConclusionWMH group exhibit narrower retinal arteries, smaller arteriole-to-venule ratio, damaged p-RNFL and visual function. These alterations in retinal vessels are associate with both neuroimaging and cognitive function. Our results suggest that retinal imaging could serve as a valuable instrument for evaluating WMH and provides some new approaches to study the characteristic markers of WMH.

Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging

To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Taiwan Biobank, we calculated the polygenic risk score (PRS) for SCZ (PRSSCZ) and BPD (PRSBPD), shared PRS between SCZ and BPD (PRSSCZ+BPD), and SCZ-specific PRS (PRSSCZvsBPD). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRSSCZ was split into PRSSCZ_concordant/PRSSCZ_discordant, and PRSBPD was split into PRSBPD_concordant/PRSBPD_discordant. Ordinal logistic regression models were used to estimate the association with educational attainment. Linear regression models were used to estimate the associations with cognitive aging (n = 27,005), measured by the Mini-Mental State Examination (MMSE), and with MMSE change (n = 6194 with mean follow-up duration of 3.9 y) in individuals aged≥ 60 years. PRSSCZ, PRSBPD, and PRSSCZ+BPD were positively associated with educational attainment, whereas PRSSCZvsBPD was negatively associated with educational attainment. PRSSCZ was negatively associated with MMSE, while PRSBPD was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRSSCZ_concordant and PRSBPD_concordant mainly determined these effects mentioned above. PRSSCZvsBPD predicted decreases in the MMSE scores. Using a large collection of community samples, this study provided evidence for the contrasting effects of polygenic architecture in SCZ and BPD on educational attainment and cognitive aging and suggested that SCZ and BPD were not genetically homogeneous.

Changes in choroidal thickness quantified by Optical Coherence Tomography across cognitive impairment: data from the NORFACE cohort

BackgroundOptical coherence tomography (OCT) enables high-resolution imaging of ocular structures in health and disease. Choroid thickness (CT) is a key vascular retinal parameter that can be assessed by OCT and might be relevant in the evaluation of the vascular component of cognitive decline. We aimed to investigate CT changes in a large cohort of individuals cognitive unimpaired (CU), with mild cognitive impairment due to Alzheimer's (MCI-AD), mild cognitive impairment due to cerebrovascular disease (MCI-Va), Alzheimer’s disease dementia (ADD), and vascular dementia (VaD).MethodsClinical, demographical, ophthalmological and OCT data from the Neuro-ophthalmological Research at Fundació ACE (NORFACE) project were analyzed. CT was assessed in the macula across nine Early Treatment Diabetic Retinopathy Study (ETDRS) quadrants, average thickness, total volume, and subfoveal choroidal thickness. Differences of CT among the five diagnostic groups were assessed in a multivariate regression model, adjusting for demographic and cardiovascular risk factors and OCT image quality. A comparison between manual and automatic CT measurements in a subset of participants was also performed.ResultsThe study cohort comprised 1,280 participants: 301 CU, 196 MCI-AD, 112 MCI-Va, 578 ADD, and 93 VaD. CT was significantly increased in individuals with cognitive impairment compared to those CU, particularly in the VaD and MCI-Va groups and in the peripheral ETDRS regions. No significant differences were found in inner superior, center and subfoveal choroidal thickness. The interaction of sex and diagnosis had no effect in differentiating CT. Mini-Mental State Examination (MMSE) scores were not correlated to CT. Manual and automated CT measurements showed good reliability.DiscussionOur findings indicated that peripheral choroidal thickening, especially in patients with cerebrovascular disease, may serve as a potential choroidal biomarker for cognitive decline and suggest different pathogenic pathways in AD and VaD. Further research is required to explore CT as a reliable ocular biomarker for cognitive impairment.

Erythropoietin for the prevention of postoperative neurocognitive disorder in older adult patients undergoing total joint arthroplasty: a randomized controlled study

BackgroundPost-operative delirium (PD) is a common post-operative complication with significant clinical and financial impacts on patients. Erythropoietin (EPO), a multi-functional glycoprotein hormone, exhibits erythropoietic and non-erythropoietic anti-inflammatory properties. This study aimed to determine the role of perioperative EPO administration in the development of postoperative delirium in older adult patients undergoing total joint arthroplasty.MethodsSeventy-one patients (> 65 years old) scheduled for total joint arthroplasty were randomly assigned to two groups: EPO-treated (EPO, n = 35) and placebo (control, n = 36). All patients completed the Mini Mental State Examination (MMSE) pre-operatively and on post-operative day (POD) 2. The confusion assessment method (CAM) was used to assess the patients until discharge (POD 5). Serum C-reactive protein (CRP) and inflammatory cytokine levels were measured and compared pre- and post-operatively. The development of delirium and cognitive dysfunction was evaluated post-operatively.ResultsOne patient in the control group developed delirium on POD 2 (3.2%), whereas no patient in the EPO group developed PD (0% vs. 3.2%, p = 0.500). Post-operatively there was no significant difference in MMSE scores between groups. Both groups showed increases in pro- and anti-inflammatory cytokine levels, with no significant differences. Similarly, CRP levels, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) showed no intergroup differences in post-operative inflammatory responses.ConclusionsPerioperative EPO reduced the incidence of post-operative delirium, although not statistically significant, with no differences in post-operative cognitive function and inflammatory responses.Trial registrationThe trial was registered on December 12, 2023 at http//clinicaltrials.gov, registration number NCT06178835.

Effects of whey-derived lactopeptide β-lactolin on cognitive performance in mild cognitive impairment: a randomized, double-blind, placebo-controlled trial

ABSTRACT Objective This study aimed to investigate the effects of a long-term intervention with β-lactolin, a tetrapeptide (sequence: glycine-threonine-tryptophan-tyrosine) derived from milk, on cognitive performance in individuals with mild cognitive impairment (MCI). Methods A randomized, double-blind, placebo-controlled trial was conducted. We recruited 48 participants aged 50 years or older with the Japanese version of the Mini-Mental State Examination (MMSE-J) score of 24–28 and a Clinical Dementia Rating (CDR) score of 0.5. Participants were administered β-lactolin (1.8 mg daily) or placebo for 24 weeks. The primary outcomes were the MMSE-J and the Japanese version of the Montreal Cognitive Assessment (MoCA-J) scores for cognitive function. Results A total of 422 individuals were screened, 48 of whom were included in this study. The MMSE-J and MoCA-J scores showed no significant differences between the groups. In the intra-group comparison of the MoCA-J delayed recall score, a significant difference was observed in the β-lactolin group after 12 and 24 weeks of intervention (p = 0.0256, p = 0.0175, respectively). Furthermore, the subgroup analysis stratified for females only showed a significant difference in MoCA-J total score in the β-lactolin group after 24 weeks of intervention (p = 0.0253). Conclusion β-lactolin intake does not significantly improve cognitive function in MCI in an inter-group comparison; nevertheless, the MoCA-J delayed recall score was significantly improved in the β-lactolin group. The number of participants was lower than planned, limiting the confirmation of the effectiveness of β-lactolin on MCI. This report demonstrated the effect size of β-lactolin intervention in MCI, contributing insights for future research.

Association between functional disability and mental health among Chinese older adults: Examining the moderating effects of social participation and physical exercise

BackgroundFunctional disability significantly burdens healthcare services, negatively affecting older adults’ social interaction and quality of life. This study aims to identify the association between functional disability and mental health, and examine the moderating effects of social participation and physical exercise on the association.MethodsThe data were drawn from 2018 wave of Chinese Longitudinal Healthy Longevity Survey, and ordinary least squares regression model was exploited to explore the association between functional disability and mental health.ResultsActivity of daily living (ADL) disability negatively predicted mini-mental state examination (MMSE) score. Furthermore, social participation and physical exercise moderated the association between ADL disability and MMSE score.ConclusionThe results highlight the importance of social participation and physical exercise for the older adults with ADL disability.

Effects of pericapsular nerve group block on early postoperative cognitive function in older people undergoing hip arthroplasty: a randomized controlled clinical trial

BackgroundPericapsular nerve group (PENG) block has emerged as a reliable analgesia technique for hip arthroplasty (HA). However, the effects of PENG block on perioperative neurocognitive disorder (PND) after HA has not yet been assessed. The present study aimed to investigate the effects of PENG block on early postoperative cognitive function in older people undergoing hip arthroplasty.MethodsSixty older patients undergoing HA under spinal anesthesia were randomly assigned to group P (n = 30) receiving PENG block with ropivacaine and patient-controlled intravenous analgesia (PCIA) pump with sufentanil after surgery or group C (n = 30) only receiving PCIA pump with sufentanil after surgery. The primary outcome was the Mini-Mental State Examination (MMSE) score at 7 days postoperatively. Secondary outcomes consisted of the incidence of PND 7 days postoperatively, the static VAS pain scores at 6, 12, 24, and 48 h postoperatively; cumulative sufentanil consumption and the requirement of rescue analgesia during the 0–24 h period after surgery; quality of recovery-15 (QoR-15) scale scores at 24 h postoperatively; and the plasma levels of high mobility group box protein 1 (HMGB1) preoperatively and 1 day after surgery, and adverse events.ResultsAfter surgery, the PENG block group had higher MMSE score than the control group at 7 days postoperatively (27.0 ± 1.8 vs. 26.1 ± 1.7, P = 0.048), with a mean difference of 0.9 (95%CI, 0.1–0.9). The incidence of PND at 7 days postoperatively was 6.7% in group P, lower than that of 30% in group C (P = 0.044). In group P, the static VAS scores at 6, 12, and 24 h postoperatively were significantly lower than those in group C (all P < 0.05). Compared with group C, the cumulative sufentanil consumption and the number of patients required rescue analgesia during the 0–24 h period after surgery were significantly lower in group P (all P < 0.05). The scores of QoR-15 scale were higher in group P at 24 h postoperatively than those in group C (P < 0.05). Patients in group P showed lower plasma levels of HMGB1 than group C at 1 day after surgery (P < 0.05), and the rate of complications didn’t differ between both groups.ConclusionsOlder people undergoing HA receiving a PENG block for perioperative analgesia experience improved early postoperative cognitive function, reduced postoperative pain, higher quality of recovery, and less postoperative inflammatory response.Trial registrationChictr.org.cn identifier ChiCTR2200061055 (Date of registry: 15/06/2022, prospectively registered).