Subjective Cognitive Impairment Research Articles

A history of abuse is associated with more severe migraine- and pain-related disability: Results from the American Registry for Migraine Research.

Prior studies have established an association between a history of abuse and more severe migraine presentation. This cross-sectional, observational study of a clinic-based migraine population used validated measures to elucidate migraine-specific and migraine-related burdens among patients with a history of abuse. Patients with migraine (n = 866) from the American Registry for Migraine Research self-reported if they had a history of emotional, physical, and/or sexual abuse and completed questionnaires assessing migraine-related burden: Migraine Disability Assessment, Subjective Cognitive Impairment Scale for Migraine Attacks, Work Productivity and Activity Impairment, Patient-Reported Outcomes Measurement Information System Pain Interference, Patient Health Questionnaire-2, and Generalized Anxiety Disorder-7. Migraine-related burden in patients with versus without a history of abuse was compared. Subsequently, a mediation analysis evaluated the impact of depression and anxiety symptoms in the relationship between abuse history and migraine burden. A history of abuse was reported by 36.5% (n = 316/866) of participants. After controlling for patient age, sex, years lived with headache, and headache frequency, a history of abuse was significantly associated with more severe migraine-related disability. The combined burden of depression and anxiety symptoms mediated the relationship. A history of abuse is associated with greater migraine-related disability. Future studies should determine if identification and management of the psychological and physical sequelae of abuse reduce migraine burden.

Methods for assessment of rey auditory verbal learning test performance in memory clinic patients and healthy adults - at the cross-roads of learning theory and clinical utility

Background: Knowledge is still lacking regarding the preferred method for evaluation of learning in the Rey Auditory Verbal Learning Test (RAVLT). Validity of different methods was examined by the effect size in differentiating diagnostic stages in memory clinic patients versus healthy adults and the strength of association between RAVLT performance and brain atrophy. Method: The study included individuals with dementia (n = 247), Mild Cognitive Impairment (MCI, n = 709), Subjective Cognitive Impairment (SCI, n = 175) and cognitively unimpaired adults serving as healthy controls (HC, n = 102). All patients went through a comprehensive clinical examination and neuropsychological assessment of cognition including episodic memory gauged with RAVLT and brain imaging of medial temporal atrophy, cortical atrophy, and white matter hyperintensity. Results: The standard method for evaluation of learning in RAVLT (summed score over five trials) together with the late learning method (mean of trials 4 and 5) were the two most powerful methods according to group differentiation (discriminant validity). Both methods also showed considerable association with medial temporal atrophy (construct validity). The initial RAVLT performance represented by results on trial 1 and the constant in regression analysis with the power function provided information regarding attention that was important for the separation of SCI and HC. Conclusions: The most favorable clinical utility was indicated by discriminant and construct validity by total learning (standard method) including both attention- and learning-related parts and late learning of RAVLT performance, while theoretical understanding of mental processes involved in RAVLT performance was provided by the distinction between initial versus the subsequent learning performance.

The Prognostic Test Accuracy of the Short and Standard Forms of the Montreal Cognitive Assessment.

Cognitive impairment is a critical concern in stroke care, and international guidelines recommend early cognitive screening. The aim of this study was to determine the prognostic accuracy of both the short and standard forms of the Montreal Cognitive Assessment (MoCA) in predicting long-term cognitive recovery following a stroke. For this study, we used data from the Efficacy of Fluoxetine - a Randomized Controlled Trial in Stroke (EFFECTS) study, which encompassed stroke patients from 35 Swedish centers over the period from 2014 to 2019. Cognitive assessments were initially conducted at 2-15 days post-stroke, with follow-up data gathered at 6 months. We used the MoCA for objective cognitive evaluation. For assessing subjective cognitive impairment, we used the memory and thinking domain of the Stroke Impact Scale. For psychometric evaluation of the short Swedish version of MoCA (s-MoCA-SWE), we used cross tables and binary logistic regression. The study included 1,141 patients (62.2% men; median [interquartile range; IQR] age, 72.3 [13.2] years; median [IQR] stroke severity, 3.0 [3.0]). At baseline, the prevalence of cognitive impairment was 71.7% according to the s-MoCA-SWE (≤12) and 67.0% according to the MoCA (≤25). The s-MoCA-SWE demonstrated a sensitivity of 92.3% for correctly identifying patients with objective cognitive impairment and 81.5% for identifying those with subjective impairments at 6 months. Although the s-MoCA-SWE had higher sensitivity, the MoCA had a more balanced sensitivity and specificity in detecting both subjective and objective cognitive impairments. In both crude and multivariable models, the s-MoCA-SWE was more strongly associated than the MoCA with cognitive impairment at 6 months. Both the short and standard versions of the MoCA appear to be effective in identifying individuals likely to experience persistent cognitive issues following a stroke. Considering the limited time available in an acute stroke unit, the short-form version may be more practical. Nevertheless, further prospective studies are required to validate these findings.

Long-term sequelae after viral meningitis and meningoencephalitis are frequent, even in mildly affected patients, a prospective observational study.

An increasing number of studies demonstrate that viral meningitis and meningoencephalitis, even those with a mild course of meningitis, can result in residual sequelae. We aimed to investigate the long-term outcome in both viral meningitis and meningoencephalitis/encephalitis patients and impact of long-term sequelae on patients' social and professional daily lives in a prospective observational study with a follow-up period of 20 months. A total of 50 patients (12% encephalitis, 58% meningoencephalitis and 30% meningitis) and 21 control persons participated in the study. The most common cause was the tick-borne encephalitis (TBE) virus. The most important persistent signs and symptoms after 2 years were subjective cognitive impairment (36%), fatigue and/or excessive daytime sleepiness (31%), disturbed nighttime sleep (31%) and headaches (13%), as well as feeling more rapidly exhausted after cognitive effort (53%). Independent of disease severity in the acute phase, almost one third of patients still reported mildly impaired social and/or professional life due to the long-term sequelae, with scores in the health status assessment still significantly lower compared to healthy controls. Regardless of the severity of the acute illness and despite constant improvement within 2 years, 67% of patients still had persistent signs and symptoms, but these were only relevant to everyday social or professional life in about 30% of these patients.

Cognitive Speed in Neurodegenerative Disease: Comparing Mean Rate and Inconsistency Within and Across the Alzheimer's and Lewy Body Spectra in the COMPASS-ND Study.

Alzheimer's disease (AD) and Lewy body disease (LBD) are characterized by early and gradual worsening perturbations in speeded cognitive responses. Using simple and choice reaction time tasks, we compared two indicators of cognitive speed within and across the AD and LBD spectra: mean rate (average reaction time across trials) and inconsistency (within person variability). The AD spectrum cohorts included subjective cognitive impairment (SCI, n = 28), mild cognitive impairment (MCI, n = 121), and AD (n = 45) participants. The LBD spectrum included Parkinson's disease (PD, n = 32), mild cognitive impairment in PD (PD-MCI, n = 21), and LBD (n = 18) participants. A cognitively unimpaired (CU, n = 39) cohort served as common benchmark. We conducted multivariate analyses of variance and discrimination analyses. Within the AD spectrum, the AD cohort was slower and more inconsistent than the CU, SCI, and MCI cohorts. The MCI cohort was slower than the CU cohort. Within the LBD spectrum, the LBD cohort was slower and more inconsistent than the CU, PD, and PD-MCI cohorts. The PD-MCI cohort was slower than the CU and PD cohorts. In cross-spectra (corresponding cohort) comparisons, the LBD cohort was slower and more inconsistent than the AD cohort. The PD-MCI cohort was slower than the MCI cohort. Discrimination analyses clarified the group difference patterns. For both speed tasks, mean rate and inconsistency demonstrated similar sensitivity to spectra-related comparisons. Both dementia cohorts were slower and more inconsistent than each of their respective non-dementia cohorts.

Brain-targeting autoantibodies in patients with dementia.

Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer's disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies.

The McCusker Subjective Cognitive Impairment Inventory (McSCI): a novel measure of perceived cognitive decline.

Subjective cognitive decline (SCD), i.e. self/other-reported concerns on one's cognitive functioning without objective evidence of significant decline, is an indicator of dementia risk. There is little consensus on reliability and validity of the available SCD measures. Therefore, introducing a novel and psychometrically sound measure of SCD is timely. The psychometric properties of a new SCD measure, the McCusker Subjective Cognitive Impairment Inventory-Self-Report (McSCI-S), are reported. Through review of previously published measures as well as our clinical and research data on people with SCD, we developed a 46-item self-report questionnaire to assess concerns on six cognitive domains, namely, memory, language, orientation, attention and concentration, visuoconstruction abilities and executive function. The McSCI-S was examined in a cohort of 526 participants using factor analysis, item response theory analysis and receiver operating characteristic (ROC) curve. A unidimensional model provided acceptable fit (CFI = 0.94, TLI = 0.94, RMSEA [90% CI] = 0.052 [.049, 0.055], WRMR = 1.45). The McSCI-S internal consistency was excellent (.96). A cut-off score of ≥24 is proposed to identify participants with SCDs. Higher McSCI-S scores were associated with poorer general cognition, episodic verbal memory, executive function and greater memory complaints and depressive scores (P < .001), controlling for age, sex and education. Excellent reliability and construct validity suggest the McSCI-S estimates SCDs with acceptable accuracy while capturing self-reported concerns for various cognitive domains. The psychometric analysis indicated that this measure can be used in cohort studies as well as on individual, clinical settings to assess SCDs.

Correlation between cancer-related cognitive impairment and resting cerebral glucose metabolism in patients with ovarian cancer

BackgroundAn increasing number of research have applied neuroimaging techniques to explore the potential neurobiological mechanism of Cancer-related cognitive impairment (CRCI). PurposeTo explore the correlation between resting brain glucose metabolism and CRCI using 18F-FDG PET/CT in ovarian cancer (OC) patients. MethodsFrom December 2021 to March 2022, 38 patients with OC were selected as the study group, and 38 healthy women of the same age (±1 year) who underwent routine physical examination using PET/CT were selected as the control group. Patients received further assessment with the Montreal Cognitive Assessment Scale (MoCA) and Perceived Deficit Questionnaire (PDQ). Independent sample t-test and Spearman correlation were conducted for data analysis. ResultsThe resting brain glucose metabolism in the OC group was significantly lower than in the healthy controls. 60.52 % patients had neuropsychological impairment and retrospective memory were the most serious perceived cognitive impairments. The resting brain glucose metabolism in OC patients did not significantly correlate with neuropsychological performance but had significant positive correlation with subjective cognitive evaluation. DiscussionResting glucose metabolism was low in OC patients and associated with subjective cognitive impairment but not objective neuropsychological test results. 18F-FDG PET/CT can be used to evaluate brain function in OC patients and provide reliable imaging indicators for early recognition of and intervention for changes in cognitive function.

Volumetric and functional connectivity changes of the thalamic nuclei in different stages of Alzheimer’s disease

ObjectiveMemory processes known to be impaired in Alzheimer’s disease (AD) are maintained by a large-scale neurocognitive network with subcortical components, including the thalamus. Therefore, we aimed to examine the volumetric and functional changes of the thalamic nuclei at different scales across AD stages. MethodsMRI data of patients diagnosed with 20 AD dementia (ADD), 30 amnestic mild cognitive impairment (MCI), and 30 subjective cognitive impairment (SCI) were used. Volumetric and functional connectivity analyzes were performed by dividing the thalamus into anterior, medial, posterior, lateral and intralaminar nucleus groups and their specific subnuclei. ResultsIn the course of AD, the volume of the medial group nuclei, especially the mediodorsal medial magnocellular (MDm) nucleus, decreases. Medial group nuclei and MDm functional connectivity with frontal areas were decreased both in ADD and MCI compared to SCI group, while both of them increased their functional connectivity with visual areas in the ADD group compared to the MCI group. ConclusionsOur study suggests that the medial group of the thalamus, and specifically the MDm, may be affected in AD. SignificanceSpecific thalamic nuclei may be a critical anatomical region for investigating structural and functional changes in AD.

Clinically feasible automated MRI volumetry of the brain as a prognostic marker in subjective and mild cognitive impairment.

The number of patients suffering from cognitive decline and dementia increases, and new possible treatments are being developed. Thus, the need for time efficient and cost-effective methods to facilitate an early diagnosis and prediction of future cognitive decline in patients with early cognitive symptoms is becoming increasingly important. The aim of this study was to evaluate whether an MRI based software, NeuroQuant® (NQ), producing volumetry of the hippocampus and whole brain volume (WBV) could predict: (1) conversion from subjective cognitive decline (SCD) at baseline to mild cognitive impairment (MCI) or dementia at follow-up, and from MCI at baseline to dementia at follow-up and (2) progression of cognitive and functional decline defined as an annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. MRI was performed in 156 patients with SCD or MCI from the memory clinic at Oslo University Hospital (OUH) that had been assessed with NQ and had a clinical follow-up examination. Logistic and linear regression analyses were performed with hippocampus volume and WBV as independent variables, and conversion or progression as dependent variables, adjusting for demographic and other relevant covariates including Mini-Mental State Examination-Norwegian Revised Version score (MMSE-NR) and Apolipoprotein E ɛ4 (APOE ɛ4) carrier status. Hippocampus volume, but not WBV, was associated with conversion to MCI or dementia, but neither were associated with conversion when adjusting for MMSE-NR. Both hippocampus volume and WBV were associated with progression as measured by the annual change in CDR-SB score in both unadjusted and adjusted analyses. The results indicate that automated regional MRI volumetry of the hippocampus and WBV can be useful in predicting further cognitive decline in patients with early cognitive symptoms.

APOLLOE4 Phase 3 study of oral ALZ-801/valiltramiprosate in APOE ε4/ε4 homozygotes with early Alzheimer's disease: Trial design and baseline characteristics.

The approved amyloid antibodies for early Alzheimer's disease (AD) carry a boxed warning about the risk of amyloid-related imaging abnormalities (ARIAs) that are highest in apolipoprotein E (APOE) ε4/ε4 homozygotes. ALZ-801/valiltramiprosate, an oral brain-penetrant amyloid beta oligomer inhibitor is being evaluated in APOE ε4/ε4 homozygotes with early AD. This Phase 3 randomized, double-blind, placebo-controlled, 78-week study of ALZ-801 administered as 265mg twice per day tablets, enrolled 50- to 80-year-old homozygotes with Mini-Mental State Examination (MMSE) ≥ 22 and Clinical Dementia Rating-Global Score 0.5 or 1.0. The study is powered to detect a 2.0 to 2.5 drug-placebo difference on the Alzheimer's Disease Assessment Scale 13-item Cognitive subscale primary outcome with 150 subjects/arm. The key secondary outcomes are Clinical Dementia Rating-Sum of Boxes and Instrumental Activities of Daily Living; volumetric magnetic resonance imaging and fluid biomarkers are additional outcomes. The APOLLOE4 Phase 3 trial enrolled 325 subjects with a mean age of 69 years, 51% female, MMSE 25.6, and 65% mild cognitive impairment. Topline results are expected in 2024. APOLLOE4 is the first disease-modification AD trial focused on APOE ε4/ε4 homozygotes. Oral ALZ-801 has the potential to be the first effective and safe anti-amyloid treatment for the high-risk APOE ε4/ε4 population. The APOLLOE4 Phase 3, placebo-controlled, 78-week study is designed to evaluate the efficacy and safety of ALZ-801 265mg twice per day in early Alzheimer's disease (AD) subjects with the apolipoprotein E (APOE) ε4/ε4 genotype.The enrolled early AD population (N=325) has 51% females, a mean age = 69 years, and a mean Mini-Mental State Examination = 25.6, with the majority being mild cognitive impairment subjects, a similar disease stage to the lecanemab Phase 3 AD trial (Clarity AD).The primary outcome is the cognitive Alzheimer's Disease Assessment Scale 13-item Cognitive subscale, with two functional measures as key secondary outcomes (Clinical Dementia Rating-Sum of Boxes, Amsterdam-Instrumental Activities of Daily Living), and with hippocampal volume and fluid biomarkers as additional outcomes.The study is unique in allowing a large number of microhemorrhages or siderosis at baseline magnetic resonance imaging, lesions that indicate concomitant cerebral amyloid angiopathy (CAA).At baseline, 32% of the enrolled population had at least 1 microhemorrhage, 24% had 1 to 4, and 8% had > 4 microhemorrhages; 10% had at least 1 siderosis lesion; with more males than females having microhemorrhages (63% vs. 37%) and siderosis (68% vs. 32%).Study results will become available in the second half of 2024 and, if positive, ALZ-801 may become the first oral drug to demonstrate a favorable benefit/risk profile in APOE ε4/ε4 AD subjects.

Siamese Graph Convolutional Network quantifies increasing structure-function discrepancy over the cognitive decline continuum

Background and Objective:Alzheimer’s disease dementia (ADD) is well known to induce alterations in both structural and functional brain connectivity. However, reported changes in connectivity are mostly limited to global/local network features, which have poor specificity for diagnostic purposes. Following recent advances in machine learning, deep neural networks, particularly Graph Neural Network (GNN) based approaches, have found applications in brain research as well. The majority of existing applications of GNNs employ a single network (uni-modal or structure/function unified), despite the widely accepted view that there is a nontrivial interdependence between the brain’s structural connectivity and the neural activity patterns, which is hypothesized to be disrupted in ADD. This disruption is quantified as a discrepancy score by the proposed “structure-function discrepancy learning network” (sfDLN) and its distribution is studied over the spectrum of clinical cognitive decline. The measured discrepancy score is utilized as a diagnostic biomarker and is compared with state-of-the-art diagnostic classifiers. Methods:sfDLN is a GNN with a siamese architecture built on the hypothesis that the mismatch between structural and functional connectivity patterns increases over the cognitive decline spectrum, starting from subjective cognitive impairment (SCI), passing through a mid-stage mild cognitive impairment (MCI), and ending up with ADD. The structural brain connectome (sNET) built using diffusion MRI-based tractography and the novel, sparse (lean) functional brain connectome (ℓNET) built using fMRI are input to sfDLN. The siamese sfDLN is trained to extract connectome representations and a discrepancy (dissimilarity) score that complies with the proposed hypothesis and is blindly tested on an MCI group. Results:The sfDLN generated structure-function discrepancy scores show high disparity between ADD and SCI subjects. Leave-one-out experiments of SCI-ADD classification over a cohort of 42 subjects reach 88% accuracy, surpassing state-of-the-art GNN-based classifiers in the literature. Furthermore, a blind assessment over a cohort of 46 MCI subjects confirmed that it captures the intermediary character of the MCI group. GNNExplainer module employed to investigate the anatomical determinants of the observed discrepancy confirms that sfDLN attends to cortical regions neurologically relevant to ADD. Conclusion:In support of our hypothesis, the harmony between the structural and functional organization of the brain degrades with increasing cognitive decline. This discrepancy, shown to be rooted in brain regions neurologically relevant to ADD, can be quantified by sfDLN and outperforms state-of-the-art GNN-based ADD classification methods when used as a biomarker.

Analysis of Cerebrospinal Fluid, Plasma β-Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease Using Quantitative Systems Pharmacology Model.

ALZ-801/valiltramiprosate is an oral, small-molecule inhibitor of beta-amyloid (Aβ) aggregation and oligomer formation in late-stage development as a disease-modifying therapy for early Alzheimer's disease (AD). The present investigation provides a quantitative systems pharmacology (QSP) analysis of amyloid fluid biomarkers and cognitive results from a 2-year ALZ-801 Phase 2 trial in APOE4 carriers with early AD. The single-arm, open-label phase 2 study evaluated effects of ALZ-801 265 mg two times daily (BID) on cerebrospinal fluid (CSF) and plasma amyloid fluid biomarkers over 104 weeks in APOE4 carriers with early AD [Mini-Mental State Examination (MMSE) ≥ 22]. Subjects with positive CSF biomarkers for amyloid (Aβ42/Aβ40) and tau pathology (p-tau181) were enrolled, with serial CSF and plasma levels of Aβ42 and Aβ40 measured over 104 weeks. Longitudinal changes of CSF Aβ42, plasma Aβ42/Aβ40 ratio, and cognitive Rey Auditory Verbal Learning Test (RAVLT) were compared with the established natural disease trajectories in AD using a QSP approach. The natural disease trajectory data for amyloid biomarkers and RAVLT were extracted from a QSP model and an Alzheimer's disease neuroimaging initiative population model, respectively. Analyses were stratified by disease severity and sex. A total of 84 subjects were enrolled. Excluding one subject who withdrew at the early stage of the trial, data from 83 subjects were used for this analysis. The ALZ-801 treatment arrested the progressive decline in CSF Aβ42 level and plasma Aβ42/Aβ40 ratio, and stabilized RAVLT over 104 weeks. Both sexes showed comparable responses to ALZ-801, whereas mild cognitive impairment (MCI) subjects (MMSE ≥ 27) exhibited a larger biomarker response compared with more advanced mild AD subjects (MMSE 22-26). In this genetically defined and biomarker-enriched early AD population, the QSP analysis demonstrated a positive therapeutic effect of oral ALZ-801 265 mg BID by arresting the natural decline of monomeric CSF and plasma amyloid biomarkers, consistent with the target engagement to prevent their aggregation into soluble neurotoxic oligomers and subsequently into insoluble fibrils and plaques over 104 weeks. Accompanying the amyloid biomarker changes, ALZ-801 also stabilized the natural trajectory decline of the RAVLT memory test, suggesting that the clinical benefits are consistent with its mechanism of action. This sequential effect arresting the disease progression on biomarkers and cognitive decline was more pronounced in the earlier symptomatic stages of AD. The QSP analysis provides fluid biomarker and clinical evidence for ALZ-801 as a first-in-class, oral small-molecule anti-Aβ oligomer agent with disease modification potential in AD. https://clinicaltrials.gov/study/NCT04693520.

Brain age as a biomarker for pathological versus healthy ageing – a REMEMBER study

ObjectivesThis study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions.MethodsThe REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject.ResultsMCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p < .001) and BPAD (r = -0.26,p < .001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p = .014) and moderate (p = .040) drinkers.ConclusionsBrain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health.

Cardiovascular and lifestyle risk factors of mild cognitive impairment in UK veterans and non-veterans.

The link between poor cardiovascular health (CVH), lifestyle and mild cognitive impairment (MCI) has been well established in the general population. However, there is limited research exploring these associations in ageing UK veterans. This study explored the risk of MCI and its association with nine CVH and lifestyle risk factors (including diabetes, heart disease, high cholesterol, high blood pressure, obesity, stroke, physical inactivity, the frequency of alcohol consumption and smoking) in UK veterans and non-veterans. This prospective cohort study comprised data from the PROTECT study between 2014 and 2022. Participants comprised of UK military veterans and non-veterans aged ≥50 years at baseline. Veteran status was defined using the Military Service History Questionnaire. CVH and lifestyle risk factors were defined using a combination of self-report measures, medication history or physical measurements. MCI was defined as the presence of subjective and objective cognitive impairment. Based on a sample of 9378 veterans (n = 488) and non-veterans (n = 8890), the findings showed the risk of MCI significantly reduced in veterans with obesity, those who frequently consumed alcohol and were physically inactive compared to non-veterans. The risk of MCI significantly increased in veterans with diabetes (hazards ratio [HR] = 2.22, 95% confidence interval [CI] 1.04-4.75, P ≤ 0.05) or high cholesterol (HR = 3.11, 95% CI 1.64-5.87, P ≤ 0.05) compared to veterans without. This study identified CVH and lifestyle factors of MCI in UK veterans and non-veterans. Further work is needed to understand these associations and the underpinning mechanisms which could determine intervention strategies to reduce the risk of MCI.

Individual and additive-effect relationships of menopausal symptoms and subjective cognitive decline among nurses during menopausal transition: a cross-sectional study.

This study aimed to examine the individual and additive-effect relationships between menopausal symptoms and subjective cognitive decline among nurses during menopausal transition. Between February and September 2019, a convenience sampling strategy was used, involving 1,335 Chinese nurses undergoing menopausal transition. A general information survey that included the Subjective Cognitive Decline Scale and the Menopause Rating Scale was completed. Based on a cut-off point of the subjective cognitive decline score of 7.5, the overall sample was divided into mild and severe groups. Propensity score matching was performed to balance covariates of mild and severe subjective cognitive decline. The individual and cumulative effects of menopausal symptoms and subjective cognitive decline were analyzed using binary logistic regression and the Cochran-Armitage trend test, respectively. After propensity score matching, none of the parameters showed significant differences between the groups. Logistic regression analysis revealed that four menopausal symptoms were closely associated with severe subjective cognitive decline. The Cochran-Armitage trend test indicated odds ratios linking the presence of these symptoms with increased severe subjective cognitive impairment. In addition, nurses simultaneously experiencing two or more core menopausal symptoms were over six times more likely to have severe subjective cognitive decline than nurses experiencing none or one core menopausal symptom during menopausal transition. Individual and additive numbers of menopausal symptoms significantly influenced subjective cognitive decline in nurses during their menopausal transition. These findings suggest that interventions aimed at enhancing the cognitive performance of nurses experiencing menopause should consider menopausal symptoms.

Effect of probiotics on cognitive function in adults with mild cognitive impairment or Alzheimer's disease: A meta-analysis of randomized controlled trials

BackgroundRecent clinical studies have yielded controversial results regarding the effect of probiotics on cognitive function in Alzheimer's disease (AD) or mild cognitive impairment (MCI) subjects. To clarify the efficacy of probiotics on cognition, we conducted a meta-analysis of randomized controlled trials (RCTs). MethodsInstructions of the PRISMA 2020 statement were followed. Literature from the PubMed, Embase and Cochrane databases were systematically searched and manually screened for relevant published RCTs. We performed statistical analysis using RevMan, and assessed the risk of bias using the R software. ResultsA total of 12 studies comprising 852 patients with MCI or AD were identified. The results of meta-analysis showed that probiotics improved global cognitive function (SMD=0.67; 95% CI, 0.32, 1.02), recall/delayed memory (SMD=0.67; 95% CI: 0.32, 1.02), attention (SMD=0.31; 95% CI: 0.04, 0.58) and visuospatial/constructional (SMD=0.24; 95% CI: 0.06, 0.42) cognitive domain. ConclusionThis meta-analysis found that probiotic supplementation is associated with an improvement in cognitive performance among patients with AD and MCI. However, current evidence is limited, and more reliable large-scale RCTs with higher methodological quality are needed.

Characterization of cancer survivors clustered by subjective and objective cognitive function scores.

Cancer-related cognitive impairment (CRCI) is a prevalent condition that significantly impacts the quality of life of individuals who receive cancer treatment. Clinical management of CRCI presents challenges due to the absenceof a standardized assessment. This study identified clinically relevant phenotypic clusters of CRCI based on subjective and objective cognitive function scores. In this cross-sectional study, participants were clustered using the VARCLUS™ based on subjective cognitive impairment assessed through the PROMIS® version 1.0 short-form subscales of cognitive abilities and cognitive concerns and the CANTAB Cambridge Cognition® scores, which included measures of visuospatial working memory capacity, visual episodic memory, new learning, working memory, executive function, and sustained attention. Each cluster's characteristics were described using demographics, physical and psychosocial factors (physical function, affect, optimism, and social support), and psychoneurological symptoms (anxiety, depression, fatigue, neuropathic pain, and sleep disturbance). We obtained five clusters from a total of 414 participants, where 99% were female, and 93% were self-reported white. Clusters 4 and 5 showed the highest PROMIS® cognitive abilities and the lowest measures of cognitive concern, while Clusters 1 and 2 showed the lowest cognitive abilities and the highest cognitive concerns. Clusters 4 and 5 had higher education, income, employment, and higher scores in physical function, positive affect, optimism, and social support. Additionally, individuals in these clusters were less prone to experience severe cancer-related psychoneurological symptoms. Our clustering approach, combining subjective and objective cognitive function information, shows promise in identifying phenotypes that hold clinical relevance for categorizing patient presentation of CRCI and facilitating individualized management strategies.

Subjective Cognitive Impairment Can Be Detected from the Decline of Complex Cognition: Findings from the Examination of Remedes 4 Alzheimer's (R4Alz) Structural Validity.

To reveal the cognitive-control dimensions that can differentiate between adults and older adults with healthy cognition, people with subjective cognitive impairment, and people diagnosed with mild cognitive impairment by examining the factorial structure of the R4Alz tool. The study comprised 404 participants: (a) healthy adults (n = 192), (b) healthy older adults (n = 29), (c) people with SCI (n = 74), and (d) people diagnosed with MCI (n = 109). The R4Alz battery was administered to all participants, including tests that assess short-term memory storage, information processing, information updating in working memory, and selective, sustained and divided attention), task/rule-switching, inhibitory control, and cognitive flexibility. A two-factorial structural model was confirmed for R4Alz, with the first factor representing "fluid intelligence (FI)" and the second factor reflecting "executive functions (EF)". Both FI and EFs discriminate among all groups. The R4Alz battery presents sound construct validity, evaluating abilities in FI and EF. Both abilities can differentiate very early cognitive impairment (SCI) from healthy cognitive aging and MCI.

The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease.

Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer's disease (AD). To explore whether serum IGF-I is associated with magnetic resonance imaging - estimated brain white matter volumes or cognitive functions. In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I-III at baseline, and after 2 years. IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.