Psychometric properties of the Spanish version of the Chalder Fatigue Scale in clinical and general populations / Propiedades psicométricas de la versión española de la Escala de Fatiga de Chalder en población clínica y general

Objetivo: La Escala de Fatiga de Chalder (CFS) es una escala breve para evaluar fatiga que se utiliza en España, pero que no ha sido validada en su población. El objetivo del estudio fue adaptar y evaluar las propiedades psicométricas de la versión española de la CFS (Sp-CFS). Método: La muestra la conformaron 3,671 participantes (3.190 de la población general y 481 pacientes), con edades entre 18 y 86 años (M = 28.43; DT = 12.71), siendo el 67.6% mujeres. Las propiedades psicométricas de la escala se probaron en un diseño transversal utilizando validación cruzada (análisis factorial exploratorio y confirmatorio) y estimación de la invarianza (sexo y condición clínica). Resultados: Un modelo de cuatro factores (baja energía, problemas de sueño, problemas de concentración y disfunción cognitiva subjetiva) en lugar de un modelo original de dos factores (fatiga física y mental) proporcionó mejores índices de bondad de ajuste a los datos. La consistencia interna y la estabilidad de la escala fueron excelentes. Su validez convergente se apoyó en su asociación significativa con la ansiedad, la depresión, el estrés y los síntomas positivos y negativos del espectro de la psicosis. El instrumento no mostró diferencias significativas entre sexos ni condiciones clínicas, y discriminó entre la población general y los pacientes, obteniendo estos últimos puntajes significativamente mayores. Conclusiones: Sp-CFS es una escala fiable y válida para medir la fatiga en población general y clínica española.(AU)

Objective:The Chalder Fatigue Scale (CFS) is a brief self-report screening scale for fatigue that is used in Spain but has not been validated for the Spanish population. The aim of this study was to adapt and evalu-ate the psychometric properties of the Spanish version of the CFS (Sp-CFS). Method:The sample consisted of 3,671 participants (3,190 from the general population and 481 patients), aged 18 to 86 years (M=28.43; DT=12.71), 67.6% of whom were women. Psychometric properties of the scale were tested in a cross-sectional design using cross-validation (explora-tory and confirmatory factor analysis) and estimation of invariance (sex and clinical condition). Results:A four-factor model (low energy, sleep problems, concentration problems and subjective cognitive dysfunction) rather than an original two-factor model (physical and mental fatigue) pro-vided better indices of goodness of fit to the data. The internal consistencyand stability of the scale were excellent. Its convergent validity was sup-ported by its significant association with anxiety, depression, stress, and the positive and negative symptoms of the psychosis spectrum. The instru-ment did not show significant differences between sexes or clinical condi-tions, and it discriminated between the general population and the patients, with the latter obtaining significantly greater scores. Conclusions: Sp-CFS is a reliable and valid scale for measuring a transdiagnostic construct such as fatigue in Spanish general and clinical populations.(AU)

The Frequency of Neuropsychiatric Sequelae After Traumatic Brain Injury in the Global South: A systematic review and meta-analysis.

This study aimed to assess the prevalence of neuropsychiatric sequelae following traumatic brain injury (TBI) among the Western Asian, South Asian and African regions of the global south. All studies on psychiatric disturbances or cognitive impairment following TBI conducted (until August 2021) in the 83 countries that constitute the aforementioned regions were reviewed; 6 databases were selected for the literature search. After evaluating the articles using the Joanna Briggs Institute guidelines, the random effects model was used to estimate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), TBI-related sleep disturbance (TBI-SD), obsessive-compulsive disorder (OCD) and cognitive impairment. Of 56 non-duplicated studies identified in the initial search, 27 were eligible for systematic review and 23 for meta-analysis. The pooled prevalence of depression in 1,882 samples was 35.35%, that of anxiety in 1,211 samples was 28.64%, that of PTSD in 426 samples was 19.94%, that of OCD in 313 samples was 19.48%, that of TBI-SD in 562 samples was 26.67% and that of cognitive impairment in 941 samples was 49.10%. To date, this is the first critical review to examine the spectrum of post-TBI neuropsychiatric sequelae in the specified regions. Although existing studies lack homogeneous data due to variability in the diagnostic tools and outcome measures utilised, the reported prevalence rates are significant and comparable to statistics from the global north.

Serum Markers of Neurodegeneration Are Strongly Linked to Heart Failure Severity and Outcome.

BACKGROUND: Cognitive impairment is prevalent in patients with heart failure with reduced ejection fraction (HFrEF), affecting self-care and outcomes. Novel blood-based biomarkers have emerged as potential diagnostic tools for neurodegeneration. OBJECTIVES: This study aimed to assess neurodegeneration in HFrEF by measuring neurofilament light chain (NfL), total tau (t-tau), amyloid beta 40 (Aß40), and amyloid beta 42 (Aß42) in a large, well-characterized cohort. METHODS: The study included 470 patients with HFrEF from a biobank-linked prospective registry at the Medical University of Vienna. High-sensitivity single-molecule assays were used for measurement. Unplanned heart failure (HF) hospitalization and all-cause death were recorded as outcome parameters. RESULTS: All markers, but not the Aß42:Aß40 ratio, correlated with HF severity, ie, N-terminal pro-B-type natriuretic peptide and NYHA functional class, and comorbidity burden and were significantly associated with all-cause death and HF hospitalization (crude HR: all-cause death: NfL: 4.44 [95% CI: 3.02-6.53], t-tau: 5.04 [95% CI: 2.97-8.58], Aß40: 3.90 [95% CI: 2.27-6.72], and Aß42: 5.14 [95% CI: 2.84-9.32]; HF hospitalization: NfL: 2.48 [95% CI: 1.60-3.85], t-tau: 3.44 [95% CI: 1.95-6.04], Aß40: 3.13 [95% CI: 1.84-5.34], and Aß42: 3.48 [95% CI: 1.93-6.27]; P < 0.001 for all). These associations remained statistically significant after multivariate adjustment including N-terminal pro-B-type natriuretic peptide. The discriminatory accuracy of NfL in predicting all-cause mortality was comparable to the well-established risk marker N-terminal pro-B-type natriuretic peptide (C-index: 0.70 vs 0.72; P = 0.225), whereas the C-indices of t-tau, Aß40, Aß42, and the Aß42:Aß40 ratio were significantly lower (P < 0.05 for all). CONCLUSIONS: Neurodegeneration is directly interwoven with the progression of HF. Biomarkers of neurodegeneration, particularly NfL, may help identify patients potentially profiting from a comprehensive neurological work-up. Further research is necessary to test whether early diagnosis or optimized HFrEF treatment can preserve cognitive function.

[Vegetable-first eating habits are associated with a reduced risk of mild cognitive impairment in elderly diabetic patients].

OBJECTIVE: To examine the relationship between vegetable-first eating habits and the cognitive function in elderly patients with diabetes. METHODS: The subjects were outpatients with diabetes ≥60 years old at Ise Red Cross Hospital. A self-administered dementia checklist was used to assess mild cognitive impairment and dementia. The participants were asked to fill out a questionnaire on their vegetable-first eating habits and were classified into 4 groups: 0, 1, 2, and 3 times a day. The dependent variables were mild cognitive impairment and dementia, and the explanatory variable was vegetable-first eating habits (0 as a reference). RESULTS: In total, 358 patients were included in the analysis. The number of vegetable-first meals was 0 in 153 (42.7%), 1 in 48 (13.4%), 2 in 46 (12.8%), and 3 in 111 (31.1%) patients. The adjusted odds ratios for 1, 2, and 3 times of mild cognitive impairment were 0.83 (95% confidence interval [CI], 0.35-1.94; P=0.680), 0.81 (95% CI, 0.32-2.00; P=0.653), and 0.37 (95% CI, 0.17-0.81; P=0.014), respectively. However, there was no significant association between vegetable-first eating habits and dementia. CONCLUSION: In elderly patients with diabetes, a vegetable-first eating habit at each meal was associated with a decreased risk of mild cognitive impairment.

[Relationship between the type and number of social participation events and the cognitive function in older diabetics].

OBJECTIVE: To examine the relationship between the type and number of social participation events and the cognitive function in elderly patients with diabetes. METHODS: The subjects were diabetic outpatients of ≥60 years of age who were managed at Ise Red Cross Hospital. Mild cognitive impairment (MCI) and dementia were assessed using a self-administered dementia checklist. Six types of social participation activities and the number of participants were investigated. A logistic regression analysis with MCI and dementia as dependent variables, social participation as an explanatory variable, and adjustment variables was used to calculate the odds ratios for social participation according to the presence of MCI and dementia. RESULTS: In total, 352 patients were included in the analysis. Volunteer activities (P=0.012), hobbies (P=0.006), activities to share skills and experiences (P=0.026), and work (P=0.003) were significantly associated with dementia. Regarding the association between the amount of social participation and dementia, there was a decrease in the risk of dementia when the number of social participation was 2. However, social participation was not significantly associated with MCI in this study. CONCLUSION: The type and number of social participation events were found to be associated with the risk of dementia in elderly patients with diabetes.

The Role of Biomarkers in Predicting Cognitive Impairment in Elderly Patients with Heart Failure.

OBJECTIVE: This study explores the impact of sST2, Growth Differentiation Factor 15 (GDF-15), and clinical factors on cognitive dysfunction in elderly patients with heart failure with reduced ejection fraction (HFrEF). METHODS: A cohort of 101 chronic stable HFrEF patients aged over 65 years old participated in the study. Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) test and the Mini Mental State Examination (MMSE). Levels of sST2, GDF-15, and N-terminal pro b-type natriuretic peptide (NT-proBNP) were also measured. RESULTS: Notably higher levels of NT-proBNP and GDF-15 were observed in the group with cognitive dysfunction, whereas sST2 levels were similar between the groups. The cognitive dysfunction group consisted of older patients. A higher proportion of patients with normal cognitive function had received influenza vaccinations. Furthermore, GDF-15 levels inversely correlated with MMSE score. Right ventricular diameter was negatively correlated, while hemoglobin levels were positively correlated with both MoCA and MMSE scores. Logistic regression analysis identified increased GDF-15 levels, older age, and advanced New York Heart Association (NYHA) classes as predictors of higher cognitive dysfunction risk, whereas influenza vaccination was linked to a reduced risk of cognitive dysfunction. CONCLUSION: Cognitive dysfunction in elderly patients with heart failure may be influenced by factors such as age, right ventricular enlargement, anemia, NYHA functional class, and levels of GDF-15 and NT-proBNP.

Low-dose-rate induces more severe cognitive impairment than high-dose-rate in rats exposed to chronic low-dose γ-radiation.

Background: Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR). Methods: The rats were exposed to γ-irradiation at a LDR of 6 mGy/h and a HDR of 20 mGy/h for 30 days (5 h/day). Functional imaging was performed to assess the brain inflammation and blood-brain barrier (BBB) destruction of rats. Histological and immunofluorescence analyses were used to reveal the neuron damage and the activation of microglia and astrocytes in the hippocampus. RNA sequencing was conducted to investigate changes in gene expression in hippocampus. Results: The rats in the LDR group exhibited more persistent cognitive impairment than those in the HDR group. Furthermore, irradiated rats showed brain inflammation and a compromised BBB. Histologically, the number of hippocampal neurons were comparable in the LDR group but were markedly decreased in the HDR. Additionally, activated M1-like microglia and A1-like astrocytes were observed in the hippocampus of rats in the LDR group; however, only M1-like microglia were activated in the HDR group. Mechanistically, the PI3K-Akt signaling pathway contributed to the different cognitive function change between the LDR group and HDR group. Conclusion: Compared with chronic low-dose γ-irradiation at HDR, LDR induced more severe cognitive impairment which might involve PI3K/Akt signaling pathway.

The Association of Dietary Inflammatory Index and Cognitive Function in Iranian Elders.

BACKGROUND: Cognitive impairment is amongst the most substantial mental health problems in elderly people, and inflammation is an underlying mechanism for cognitive impairment. The dietary inflammatory index (DII®) reflects the overall inflammatory potential of individuals' diets. The current study aimed to assess the relationship between the DII and cognitive function among the Iranian old population. METHODS: This cross-sectional study was conducted on 221 subjects≥65 years old in healthcare centers in five socioeconomically distinct districts of Tehran, Iran. Dietary intake data were obtained using a validated food frequency questionnaire (FFQ). Energy-adjusted-DII (E-DIITM) scores were calculated for each participant according to a total of 35 food parameters, which were available from the FFQ. Mini mental state examination (MMSE), a brief screening questionnaire was used to assess cognitive function. RESULTS: E-DII scores were not significantly associated with cognitive function, both in the crude model (ß=-0.04, p-value=0.82) and after adjusting for potential confounders (ß=0.22, pvalue= 0.14). Additionally, in the unadjusted model, individuals in the highest tertile of E-DII score had increased odds of mild cognitive impairment (OR=1.13, p-trend=0.01) compared to those older adults in the lowest tertile of E-DII score. However, after controlling for potential confounders, these relationships faded (AOR=1.46, p-trend=0.12). CONCLUSION: The findings of the present study showed no significant relationship between E- DII and cognitive function among the Iranian elderly. Future prospective studies should be undertaken to explore the association between diet-associated inflammation and cognitive decline in the elderly.

Strength together: examining risk and protective factors associated with dementia and cognitive impairment in Aboriginal and Torres Strait Islander peoples through harmonisation of landmark studies.

BACKGROUND: Rates of dementia for Aboriginal and Torres Strait Islander peoples are three to five times greater compared to non-Indigenous Australians, with earlier age of onset. However, the risk and protective factors that drive these higher rates vary across existing cohort studies, with minimal findings on the role of vascular risk factors beyond stroke. Harmonisation of data across studies may offer greater insights through enhanced diversity and strengthened statistical capabilities. This study aims to combine three landmark cohort studies of Aboriginal and Torres Strait Islander participants to better understand the determinants of cognitive health and dementia. METHODS/DESIGN: Three cohort studies - the Kimberley Healthy Adults Project (KHAP, N = 363), Koori Growing Old Well Study (KGOWS, N = 336) and Torres Strait Dementia Prevalence Study (TSDPS, N = 274) - share a similar research methodology with demographic, medical history, psychosocial factors, cognitive tests and consensus clinical diagnoses of cognitive impairment and dementia. Associations between risk and protective factors of interest and the presence of dementia and/or cognitive impairment diagnoses will be evaluated by univariable and multivariable logistic regression in a harmonised cross-sectional cohort of 898 participants. Factors associated with incident dementia and/or cognitive impairment will be assessed in a subset of KHAP (n = 189) and KGOWS participants (n = 165) who were available in longitudinal follow-up, after exclusion of those with baseline dementia or cognitive impairment. Analyses in relation to outcome measure of death or dementia will be conducted to account for the competing risk of death. Logistic regression will be used to evaluate the association between the individual components of the 16-component Kimberley Indigenous Cognitive Assessment (KICA) tool and the presence of dementia and cognitive impairment determined by independent consensus diagnoses. Multivariable binary logistic regression will be used to adjust for the effect of confounding variables. Results will be reported as odds ratios (OR) with 95% confidence intervals (95% CI). DISCUSSION: Greater understanding of risk and protective factors of dementia and cognitive impairment relevant to Aboriginal and Torres Strait Islander peoples may improve approaches across the life course to delay cognitive decline and reduce dementia risk.

Locus coeruleus integrity and left frontoparietal connectivity provide resilience against attentional decline in preclinical alzheimer's disease.

BACKGROUND: Autopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and pharmacological studies reported that left frontoparietal network functional connectivity (LFPN-FC) confers resilience against beta-amyloid (Aß)-related cognitive decline in preclinical sporadic and autosomal dominant Alzheimer's disease (AD), as well as against LC-related cognitive changes. Given that the LFPN and the LC play important roles in attention, and attention deficits have been observed early in the disease process, we examined whether LFPN-FC and LC structural health attenuate attentional decline in the context of AD pathology. METHODS: 142 participants from the Harvard Aging Brain Study who underwent resting-state functional MRI, LC structural imaging, PiB(Aß)-PET, and up to 5 years of cognitive follow-ups were included (mean age = 74.5 ± 9.9 years, 89 women). Cross-sectional robust linear regression associated LC integrity (measured as the average of five continuous voxels with the highest intensities in the structural LC images) or LFPN-FC with Digit Symbol Substitution Test (DSST) performance at baseline. Longitudinal robust mixed effect analyses examined associations between DSST decline and (i) two-way interactions of baseline LC integrity (or LFPN-FC) and PiB or (ii) the three-way interaction of baseline LC integrity, LFPN-FC, and PiB. Baseline age, sex, and years of education were included as covariates. RESULTS: At baseline, lower LFPN-FC, but not LC integrity, was related to worse DSST performance. Longitudinally, lower baseline LC integrity was associated with a faster DSST decline, especially at PiB > 10.38 CL. Lower baseline LFPN-FC was associated with a steeper decline on the DSST but independent of PiB. At elevated PiB levels (> 46 CL), higher baseline LFPN-FC was associated with an attenuated decline on the DSST, despite the presence of lower LC integrity. CONCLUSIONS: Our findings demonstrate that the LC can provide resilience against Aß-related attention decline. However, when Aß accumulates and the LC's resources may be depleted, the functioning of cortical target regions of the LC, such as the LFPN-FC, can provide additional resilience to sustain attentional performance in preclinical AD. These results provide critical insights into the neural correlates contributing to individual variability at risk versus resilience against Aß-related cognitive decline.

Cognitive impairment in long-COVID.

Background and purpose:

Long Covid is a complex con­dition characterised by symptoms that per­sist for weeks and months after the Co­vid infection, accompanied by cognitive im­pairment that negatively affects daily life. Understanding this complex condition is im­portant for the development of diagnostic and therapeutic strategies.

This article aims to provide a comprehensive overview of cognitive impairment in long-COVID, including its definition, symptoms, pathophysiology, risk factors, assessment tools, imaging abnormalities, potential biomarkers, management strategies, long-term outcomes, and future directions for research.

The search methodology used in this review aimed to include a wide range of research on cognitive impairment related to both COVID-19 and long-COVID. Systematic searches of PubMed and Google Scholar databases were conducted using a mixture of MeSH terms and keywords including ‘cognition’, ‘cognitive impairment’, ‘brain fog’, ‘COVID-19’ and ‘long-COVID’. The search was restricted to studies published in English between 1 January 2019 and 11 February 2024, which presented findings on neurological manifestations in human participants.

Long-COVID is characterized by persistent symptoms following COVID-19 infection, with cognitive impairment being a prominent feature. Symptoms include brain fog, difficulties with concentration, memory issues, and executive function deficits. Pa­tho­physiological mechanisms involve vi­ral persistence, immune responses, and vas­cular damage. Risk factors include age, pre-existing conditions, and disease seve­rity. Cognitive assessment tools such as the Montreal Cognitive Assessment (MoCA) are essential for diagnosis. Imaging studies, including MRI, PET, and SPECT, reveal structural and functional brain alterations. Potential biomarkers include C-reactive protein, interleukin-6, and neuron-specific enolase. Management strategies encompass cognitive rehabilitation, occupational therapy, medications, and lifestyle modifications.

Long-COVID poses a multifaceted challenge, and cognitive impairment significantly impacts patients’ lives. A multi­disciplinary approach, including cognitive rehabilitation and medication when appropriate, is essential for effective management. Future research should focus on validating biomarkers and understanding long-term cognitive outcomes.

Conclusion – Long-COVID is a global health concern, and cognitive impairment is a distressing symptom. While pharmacological interventions have potential, they require careful consideration. Continued research is crucial for improving the understanding and treatment of cognitive impairment in long-COVID.

Regional Burden of Enlarged Perivascular Spaces and Cognition and Neuropsychiatric Symptoms in Drug-Naive Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population. METHODS: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline. Cognitive performance, NPS burden, vascular risk factors, small vessel disease (SVD) imaging markers, and DAT availability were compared across groups dichotomized by their regional EPVS burden (cutoff for high-degree vs low-degree: >10 for T-EPVS/BG-EPVS and >20 for CS-EPVS). RESULTS: A total of 480 patients with PD (123 without cognitive impairment, 291 with mild cognitive impairment, and 66 with dementia) were included. The proportion of high-degree T-EPVS (p for trend <0.001) and BG-EPVS (p for trend = 0.001) exhibited an increasing trend across the cognitive spectrum, corresponding to worsening cognition. Compared with the low-degree group, the high-degree BG-EPVS group showed higher SVD burden (moderate-to-severe white matter hyperintensity [14.8% vs 40.5%, p < 0.001], lacune [10.3% vs 30.7%, p < 0.001], and cerebral microbleeds [8.1% vs 22.2%, p < 0.001]), greater atrophy in cortical gray matter (40.73% ± 1.09% vs 39.96% ± 1.20% of intracranial volume, p < 0.001), and lower cognitive performance (in language [-0.22 ± 1.18 vs -0.53 ± 1.29, p = 0.013], and visual memory domains [-0.24 ± 0.97 vs -0.61 ± 0.96, p = 0.009]). The high-degree T-EPVS group presented with greater NPS burden in decreased motivation (0.61 ± 1.78 vs 1.35 ± 2.36, p = 0.007), affective dysregulation (0.88 ± 2.13 vs 2.36 ± 3.53, p < 0.001), and impulse dyscontrol (0.43 ± 1.67 vs 1.74 ± 4.29, p < 0.001), compared with the low-degree T-EPVS group. Meanwhile, the burden of CS-EPVS did not reveal any differences in cognition or NPS. DISCUSSION: BG-EPVS and T-EPVS seem to exert differential effects on cognition and NPS in patients with PD. Investigating the EPVS profile in distinct anatomical regions may be useful in disentangling the heterogeneity within PD.

Neural markers of reduced arousal and consciousness in mild cognitive impairment.

OBJECTIVES: People with Alzheimer's Disease (AD) experience changes in their level and content of consciousness, but there is little research on biomarkers of consciousness in pre-clinical AD and Mild Cognitive Impairment (MCI). This study investigated whether levels of consciousness are decreased in people with MCI. METHODS: A multi-site site magnetoencephalography (MEG) dataset, BIOFIND, comprising 83 people with MCI and 83 age matched controls, was analysed. Arousal (and drowsiness) was assessed by computing the theta-alpha ratio (TAR). The Lempel-Ziv algorithm (LZ) was used to quantify the information content of brain activity, with higher LZ values indicating greater complexity and potentially a higher level of consciousness. RESULTS: LZ was lower in the MCI group versus controls, indicating a reduced level of consciousness in MCI. TAR was higher in the MCI group versus controls, indicating a reduced level of arousal (i.e. increased drowsiness) in MCI. LZ was also found to be correlated with mini-mental state examination (MMSE) scores, suggesting an association between cognitive impairment and level of consciousness in people with MCI. CONCLUSIONS: A decline in consciousness and arousal can be seen in MCI. As cognitive impairment worsens, measured by MMSE scores, levels of consciousness and arousal decrease. These findings highlight how monitoring consciousness using biomarkers could help understand and manage impairments found at the preclinical stages of AD. Further research is needed to explore markers of consciousness between people who progress from MCI to dementia and those who do not, and in people with moderate and severe AD, to promote person-centred care.

The circadian syndrome is a predictor for cognition impairment in middle-aged adults: Comparison with the metabolic syndrome.

AIMS: Circadian syndrome (CircS) is considered a better predictor for cardiovascular disease than the metabolic syndrome (MetS). We aim to examine the associations between CircS and MetS with cognition in Chinese adults. METHOD: We used the data of 8546 Chinese adults aged ≥40 years from the 2011 China Health and Retirement Longitudinal Study. MetS was defined using harmonised criteria. CircS included the components of MetS plus short sleep and depression. The cut-off for CircS was set as ≥4. Global cognitive function was assessed during the face-to-face interview. RESULTS: CircS and MetS had opposite associations with the global cognition score and self-reported poor memory. Compared with individuals without the CircS and MetS, the regression coefficients (95%CI) for global cognition score were -1.02 (-1.71 to -0.34) for CircS alone and 0.52 (0.09 to 0.96) for MetS alone in men; -1.36 (-2.00 to -0.72) for CircS alone and 0.60 (0.15 to 1.06) for MetS alone in women. Having CircS alone was 2.53 times more likely to report poor memory in men (95%CI 1.80-3.55) and 2.08 times more likely in women (95%CI 1.54-2.81). In contrast, having MetS alone was less likely to report poor memory (OR 0.64 (0.49-0.84) in men and 0.65 (0.52-0.81) in women). People with CircS and MetS combined were more likely to have self-reported poor memory. CONCLUSIONS: CircS is a strong and better predictor for cognition impairment than MetS in Chinese middle-aged adults. MetS without short sleep and depression is associated with better cognition.

Lactobacillus rhamnosus GG improves cognitive impairments in mice with sepsis.

Background: Survivors of sepsis may encounter cognitive impairment following their recovery from critical condition. At present, there is no standardized treatment for addressing sepsis-associated encephalopathy. Lactobacillus rhamnosus GG (LGG) is a prevalent bacterium found in the gut microbiota and is an active component of probiotic supplements. LGG has demonstrated to be associated with cognitive improvement. This study explored whether LGG administration prior to and following induced sepsis could ameliorate cognitive deficits, and explored potential mechanisms. Methods: Female C57BL/6 mice were randomly divided into three groups: sham surgery, cecal ligation and puncture (CLP), and CLP+LGG. Cognitive behavior was assessed longitudinally at 7-9d, 14-16d, and 21-23d after surgery using an open field test and novel object recognition test. The impact of LGG treatment on pathological changes, the expression level of brain-derived neurotrophic factor (BDNF), and the phosphorylation level of the TrkB receptor (p-TrkB) in the hippocampus of mice at two weeks post-CLP (16d) were evaluated using histological, immunofluorescence, immunohistochemistry, and western blot analyses. Results: The CLP surgery induced and sustained cognitive impairment in mice with sepsis for a minimum of three weeks following the surgery. Compared to mice subjected to CLP alone, the administration of LGG improved the survival of mice with sepsis and notably enhanced their cognitive functioning. Moreover, LGG supplementation significantly alleviated the decrease in hippocampal BDNF expression and p-TrkB phosphorylation levels caused by sepsis, preserving neuronal survival and mitigating the pathological changes within the hippocampus of mice with sepsis. LGG supplementation mitigates sepsis-related cognitive impairment in mice and preserves BDNF expression and p-TrkB levels in the hippocampus.

Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies.

BACKGROUND AND OBJECTIVES: Plasma ß-amyloid-1-42/1-40 (Aß42/40), phosphorylated-tau (P-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) have been widely examined in Alzheimer disease (AD), but little is known about their reflection of copathologies, clinical importance, and predictive value in dementia with Lewy bodies (DLB). We aimed to evaluate associations of these biomarkers with CSF amyloid, cognition, and core features in DLB. METHODS: This cross-sectional multicenter cohort study with prospective component included individuals with DLB, AD, and healthy controls (HCs), recruited from 2002 to 2020 with an annual follow-up of up to 5 years, from the European-Dementia With Lewy Bodies consortium. Plasma biomarkers were measured by single-molecule array (Neurology 4-Plex E kit). Amyloid status was determined by CSF Aß42 concentrations, and cognition was assessed by Mini-Mental State Examination (MMSE). Biomarker differences across groups, associations with amyloid status, and clinical core features were assessed by analysis of covariance. Associations with cognitive impairment and decline were assessed by linear regression and linear mixed-effects models. RESULTS: In our cohort consisting of 562 individuals (HC n = 89, DLB n = 342, AD n = 131; 250 women [44.5%], mean [SD] age of 71 [8] years), sex distribution did not differ between groups. Patients with DLB were significantly older, and had less years of education and worse baseline cognition than HC, but not AD. DLB participants stratified for amyloid status differed significantly in plasma Aß42/40 ratio (decreased in amyloid abnormal: ß = -0.008, 95% CI -0.016 to -0.0003, p = 0.01) and P-tau (increased in amyloid abnormal, P-tau181: ß = 0.246, 95% CI 0.011-0.481; P-tau231: ß = 0.227, 95% CI 0.035-0.419, both p < 0.05), but not in GFAP (ß = 0.068, 95% CI -0.018 to 0.153, p = 0.119), and NfL (ß = 0.004, 95% CI -0.087 to 0.096, p = 0.923) concentrations. Higher baseline GFAP, NfL, and P-tau concentrations were associated with lower MMSE scores in DLB, and GFAP and NfL were associated with a faster cognitive decline (GFAP: annual change of -2.11 MMSE points, 95% CI -2.88 to -1.35 MMSE points, p < 0.001; NfL: annual change of -2.13 MMSE points, 95% CI -2.97 to -1.29 MMSE points, p < 0.001). DLB participants with parkinsonism had higher concentrations of NfL (ß = 0.08, 95% CI 0.02-0.14, p = 0.006) than those without. DISCUSSION: Our study suggests a possible utility of plasma Aß42/40, P-tau181, and P-tau231 as a noninvasive biomarkers to assess amyloid copathology in DLB, and plasma GFAP and NfL as monitoring biomarkers for cognitive symptoms in DLB.

Association between drinking water sources and cognitive functioning in Chinese older adults residing in rural areas.

OBJECTIVES: To explore the association between drinking water sources and cognitive functioning among older adults residing in rural China. METHODS: Data were extracted from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey. Drinking water sources were categorized according to whether purification measures were employed. The Chinese version of the Mini-Mental State Examination was used for cognitive functioning assessment, and the score of <24 was considered as having cognitive dysfunction. Cox regression analyses were conducted to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the effects of various drinking water sources, changes in such sources, and its interaction with exercise on cognition dysfunction. RESULTS: We included 2304 respondents aged 79.67 ± 10.02 years; of them, 1084 (44.49%) were men. Our adjusted model revealed that respondents consistently drinking tap water were 21% less likely to experience cognitive dysfunction compared with those drinking untreated water (HR = 0.79, 95% CI: 0.70-0.90). Respondents transitioning from natural to tap water showed were 33% less likely to experience cognitive dysfunction (HR = 0.67, 95% CI: 0.58-0.78). Moreover, the HR (95% CI) for the interaction between drinking tap water and exercising was 0.86 (0.75-1.00) when compared with that between drinking untreated water and not exercising. All results adjusted for age, occupation, exercise, and body mass index. CONCLUSIONS: Prolonged tap water consumption and switching from untreated water to tap water were associated with a decreased risk of cognitive dysfunction in older individuals. Additionally, exercising and drinking tap water was synergistically associated with the low incidence of cognitive dysfunction. These findings demonstrate the importance of prioritizing drinking water health in rural areas, indicating that purified tap water can enhance cognitive function among older adults.

Hippocampus under Pressure: Molecular Mechanisms of Development of Cognitive Impairments in SHR Rats.

Data from clinical trials and animal experiments demonstrate relationship between chronic hypertension and development of cognitive impairments. Here, we review structural and biochemical alterations in the hippocampus of SHR rats with genetic hypertension, which are used as a model of essential hypertension and vascular dementia. In addition to hypertension, dysfunction of the hypothalamic-pituitary-adrenal system observed in SHR rats already at an early age may be a key factor of changes in the hippocampus at the structural and molecular levels. Global changes at the body level, such as hypertension and neurohumoral dysfunction, are associated with the development of vascular pathology and impairment of the blood-brain barrier. Changes in multiple biochemical glucocorticoid-dependent processes in the hippocampus, including dysfunction of steroid hormones receptors, impairments of neurotransmitter systems, BDNF deficiency, oxidative stress, and neuroinflammation are accompanied by the structural alterations, such as cellular signs of neuroinflammation micro- and astrogliosis, impairments of neurogenesis in the subgranular neurogenic zone, and neurodegenerative processes at the level of synapses, axons, and dendrites up to the death of neurons. The consequence of this is dysfunction of hippocampus, a key structure of the limbic system necessary for cognitive functions. Taking into account the available results at various levels starting from the body and brain structure (hippocampus) levels to molecular one, we can confirm translational validity of SHR rats for modeling mechanisms of vascular dementia.

Understanding the lived experience research priorities for improving health-related quality of life in people living with HIV with cognitive impairment.

BACKGROUND: People living with HIV experience higher rates of cognitive impairment (CI), and at younger ages, than the general population. These individuals report poor health-related quality of life (HRQL), however, interventions aimed at assisting people living with HIV to live well with CI do not currently exist and represent an important un-met need in this population. OBJECTIVE: This study aimed to identify the lived experience research priorities for improving HRQL and identify interventions to support priority areas. METHODS: A Research Advisory Group was established with 15 lived experience, academic, healthcare, and third sector professionals. Additionally, two semi-structured focus groups were undertaken, with health and third sector professionals and people living with HIV with CI. Participants were asked to rank factors impacting HRQL, identified in prior research, in terms of priority and intervention development. Findings were analysed using a combination of conventional and summative content analysis. Study findings were feedback to our Research Advisory Group. RESULTS: Five people living with HIV with CI, recruited through third sector agencies [Male 80%; median age 59 (range 56-78); White British 60%; homosexual 60%], and three healthcare and third sector participants (66% third sector professionals from two local HIV charities; 33% HIV-specific clinical psychologist) took part in two focus groups and ranked interventions targeting improvement in physical function, social connectedness, cognition and perceived control over cognitive health as priority areas. Findings were then fed back to the Research Advisory Group who recommended the development of an illness-specific cognitive rehabilitation programme and improved information provision as important avenues for intervention development. CONCLUSION: Given the absence of meaningful patient and public involvement, intervention, and support guidelines for people living with HIV with CI, this provides a roadmap for future research in this important and growing area of HIV clinical care.