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Purpose: The aim was to investigate the associations between cognitive impairment and biopsychosocial factors among older stroke survivors and predictors of poststroke return to daily life. Materials and methods: This cross-sectional study involved 117 stroke survivors (61% men) with an average age of 77 years (range 65–91). The participants completed two questionnaires (Riksstroke and Short Form 36 questionnaires). The Montreal Cognitive Assessment (MoCA) was used to assess cognitive abilities. The International Classification of Functioning, Disability, and Health (ICF) framework guided the selection of biopsychosocial variables. We used Spearman’s correlation coefficient and multiple logistic regression in the analyses. Results: The average MoCA score was 21.7 points (range: 4–30, SD 5.6). The need for assistance from relatives and professionals, need for help with dressing and household chores, reliance on others for mobility, and reading and balance problems were correlated with more severe cognitive impairment (r = 0.20–0.33). Cognitive impairment, fatigue, and balance issues predicted an unfavorable return to daily life (odds ratio: 6.2–6.8). Conclusion: The study indicated that cognitive impairment is associated with difficulties in all ICF domains. Cognitive impairment, fatigue, and balance issues are associated with an unsuccessful return to daily life. Prioritizing these factors and screening for cognitive impairment with objective assessment tools may improve rehabilitation outcomes and enhance overall quality of life poststroke.

Background: Poor sleep is a potential modifiable risk factor for later life development cognitive impairment. The aim of this study is to examine if subjective measures of sleep duration and sleep disturbance predict future cognitive decline in a population-based cohort of 60, 66, 72 and 78-year-olds with a maximal follow up time of 18 years. Methods: This study included participants from the Swedish National Study on Ageing and Care – Blekinge, with assessments 2001–2021. A cohort of 60 (n = 478), 66 (n = 623), 72 (n = 662) and 78 (n = 548) year-olds, were assessed at baseline and every 6 years until 78 years of age. Longitudinal associations between sleep disturbance (sleep scale), self-reported sleep duration and cognitive tests (Mini Mental State Examination and the Clock drawing test) were examined together with typical confounders (sex, education level, hypertension, hyperlipidemia, smoking status, physical inactivity and depression). Results: There was an association between sleep disturbance at age 60 and worse cognitive function at ages 60, 66 and 72 years in fully adjusted models. The association was attenuated after bootstrap-analysis for the 72-year-olds. The items of the sleep scale most predictive of later life cognition regarded nightly awakenings, pain and itching and daytime naps. Long sleep was predictive of future worse cognitive function. Conclusion: Sleep disturbance was associated with worse future cognitive performance for the 60-year-olds, which suggests poor sleep being a risk factor for later life cognitive decline. Questions regarding long sleep, waking during the night, pain and itching and daytime naps should be further explored in future research and may be targets for intervention., CC BY 4.0© 2022 The AuthorsCorresponding author at: Department of Health, Blekinge Institute of Technology, Valhallavägen 1, 371 41 Karlskrona, Sweden. E-mail address: anders.behrens@bth.se (A. Behrens). SNAC is financially supported by the Ministry of Health and Social Affairs, Sweden, and the participating county councils, municipalities, and university departments.

Multidomain interventions have shown tremendous potential for improving cognition in older adults. It is unclear if multidomain interventions can be delivered remotely and whether remote intervention is beneficial for older adults who are vulnerable or at risk of cognitive decline. In a 26-week multi-site, home-based, double-blind, randomized controlled trial, 120 cognitively healthy older adults (75 robust, 45 pre-frail; age range = 60–94) recruited from Switzerland, Canada, and Belgium were randomized to receive either the StayFitLonger (SFL) computerized multidomain training program or an active control intervention. Delivered on tablets, the SFL intervention combined adapted physical exercises (strength, balance, and mobility), cognitive training (divided attention, problem solving, and memory), opportunities for social and contributive interactions, and psychoeducation. The active control intervention provided basic mobilization exercises and access to video games. Cognitive outcomes were global cognition (Z-scores of attention, verbal fluency, and episodic memory for nondemented older adults; ZAVEN), memory, executive function, and processing speed. Linear mixed model analyses indicated improved performance on the ZAVEN global cognition score in the SFL group but not in the active control group. Stratified analyses by frailty status revealed improved ZAVEN global cognition and processing speed scores following SFL in the pre-frail group but not in the robust group. Overall, the study indicates that a computerized program providing a multidomain intervention at home can improve cognition in older adults. Importantly, pre-frail individuals, who are at higher risk of cognitive decline, seem to benefit more from the intervention. Trial registration: ClinicalTrials.gov, NCT037519 Registered on January 22, 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04237519.

Abtract Functional magnetic resonance imaging (fMRI) was used to assess the effect of cognitive training on brain activation as a function of the learning phase and level of education. Forty older adults with subjective cognitive decline (SCD) received 6 1-hour memory training sessions with the method of loci. Brain imaging (N = 29) was measured during word list encoding and retrieval before training (PRE), after 3 training sessions (POST3), and after 6 training sessions (POST6). Participants showed increased activation of the left inferior pre-frontal gyrus from PRE to POST6 during encoding and reduced bilateral frontostriatal activation from PRE to POST3 during retrieval, regardless of education. Activation changes from PRE to POST3 varied as a function of education in 2 regions of the right temporal lobe: participants with lower education showed increased activation, while those with higher education showed decreased activation. These regions were initially less active in people with lower education. Results suggest a strategic shift in people with lower education and expertise building in those with higher education, along with a restoration of initial education-related differences.

Background: Sarcopenia and cognitive impairment are two leading causes of disabilities. Objective: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. Methods: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. Results: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). Conclusion: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.

Background: age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD stage at which mortality increases among older people. Methods: our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index. Results: overall, mortality was found to increase starting from eGFR = 30-44.9 ml/min/1.73 m2 (hazard ratio [HR] = 3.28, 95% confidence interval [CI] = 1.81-5.95) to ACR = 30-300 mg/g (HR = 1.96, 95%CI = 1.23-3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45-59.9 ml/min/1.73 m2, as well as patients with ACR < 30 mg/g and impaired handgrip and SPPB. Survival tree leaf node membership had greater predictive accuracy (C-index = 0.81, 95%CI = 0.78-0.84 for the eGFR survival tree and C-index = 0.77, 95%CI = 0.71-0.81 for the ACR survival tree) in comparison with that of individual measures of kidney function. Conclusions: physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild-moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function. © 2022 The Author(s). Published by Oxford University Press on behalf of the B

Background: Subjective cognitive decline (SCD) has been postulated as an early marker of Alzheimer’s Disease (AD) but it can also be associated to other non-AD pathologies such as Vascular Dementia (VaD). Nevertheless, there is scarce data about SCD as a potential harbinger of cerebrovascular pathology. Thus, we conducted a systematic review and meta-analysis on the association between SCD and cerebrovascular damage measured by neuroimaging markers. Method: This study was performed following the PRISMA guidelines. The search was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin to December 8th, 2021. Primary studies including cognitively unimpaired adults with SCD and neuroimaging markers of cerebrovascular damage (i.e., white matter signal abnormalities, WMSA) were selected. Qualitative synthesis and meta-analysis of studies with a case-control design was performed. Results: Of 241 articles identified, 21 research articles were selected. Eight case-control studies were included for the meta-analysis. A significant overall effect-size was observed for the mean WMSA burden in SCD relative to controls, where the WMSA burden was higher in SCD. Conclusion: Our findings show the potential usefulness of SCD as a harbinger of cerebrovascular disease in cognitively healthy individuals. Further research is needed in order to elucidate the role of SCD as a preclinical marker of vascular cognitive impairment.

Introduction: Neurological aspect of COVID-19 is less understood compared to its respiratory and systemic effects. We aimed to define subacute neurological sequelae in patients who recovered from mild COVID-19. Materials and Methods: This study enrolled long COVID patients who had mild infection, were non-hospitalized, and admitted to our hospital with neurological complaints occurring after COVID-19. The evaluation included detailed history of the symptoms, neurological examination, blood tests and necessary investiga-tions relevant to their personal medical situation, and also a retrospective inqu-iry about their respiratory and neurological status during the acute phase of infection. Descriptive statistical measures, Chi-square and Student’s t-test were utilized. Results: We identified 50 patients (29F/21M) with a mean age of 36.9 ± 1.6 (mean ± SEM). The average time from COVID-19 to admission was 99 days(min-max= 15-247). Most frequent neurological complaints were headache (42%) and cognitive dysfunction (42%). Sleep disturbance (36%), prolonged anosmia (30%), prolonged ageusia (22%), fatigue (22%), and dizziness (8%) followed. Most patients with headache experienced headache also as an acute manifestation of COVID-19 (p= 0.02). Acute-stage sleep disorders were found to be more associated with subacute cognitive symptoms than other central symptoms (p= 0.008). The most common neurological symptom in the acute phase was headache (74%). Six patients, despite the absence of any acute-stage neurological symptoms, presented with emergence of subacute neurological sequela. There were only five patients with pulmonary involvement during the acute stage, who were not different from the rest of the cohort in terms of neurological sequelae. There was no increase of inflammatory markers in the blood tests at the subacute stage, or no association of the symptoms to bioche-mical parameters. Conclusion: This study gives a description of neurological sequelae of mild COVID-19

Introduction: Neurological aspect of COVID-19 is less understood compared to its respiratory and systemic effects. We aimed to define subacute neurological sequelae in patients who recovered from mild COVID-19. Materials and Methods: This study enrolled long COVID patients who had mild infection, were non-hospitalized, and admitted to our hospital with neurological complaints occurring after COVID-19. The evaluation included detailed history of the symptoms, neurological examination, blood tests and necessary investiga-tions relevant to their personal medical situation, and also a retrospective inqu-iry about their respiratory and neurological status during the acute phase of infection. Descriptive statistical measures, Chi-square and Student’s t-test were utilized. Results: We identified 50 patients (29F/21M) with a mean age of 36.9 ± 1.6 (mean ± SEM). The average time from COVID-19 to admission was 99 days(min-max= 15-247). Most frequent neurological complaints were headache (42%) and cognitive dysfunction (42%). Sleep disturbance (36%), prolonged anosmia (30%), prolonged ageusia (22%), fatigue (22%), and dizziness (8%) followed. Most patients with headache experienced headache also as an acute manifestation of COVID-19 (p= 0.02). Acute-stage sleep disorders were found to be more associated with subacute cognitive symptoms than other central symptoms (p= 0.008). The most common neurological symptom in the acute phase was headache (74%). Six patients, despite the absence of any acute-stage neurological symptoms, presented with emergence of subacute neurological sequela. There were only five patients with pulmonary involvement during the acute stage, who were not different from the rest of the cohort in terms of neurological sequelae. There was no increase of inflammatory markers in the blood tests at the subacute stage, or no association of the symptoms to bioche-mical parameters. Conclusion: This study gives a description of neurological sequelae of mild COVID-19

This thesis investigates the association of acute illness hospitalisation (AIH) with posthospitalisation cognitive decline (PHCD). It includes a systematic review which summarises 24 reports with samples exposed to mixed diagnosis AIH. Eleven of these concluded that cognition was worse following AIH, both in the short term and long term. Three specifically reported an accelerated rate of decline in cognition following AIH. Meta-analysis (MA) of seven of the 24 studies (41,453 participants), demonstrated a Cohen’s d value for poorer cognition of 0.25 standard deviation units for hospitalised compared with non-hospitalised participants. Although several methodological challenges limited the generalisability of the MA, it suggested there is a long-term risk of PHCD following AIH exposure.The association of AIH exposure and cognition was investigated using the Sydney Memory and Ageing study (MAS) sample. Latent growth modelling was used to estimate global cognition latent intercept and slope from neuropsychological data in four biennial waves. Electronically linked hospitalisation data were computed in time intervals to clarify recency effects. Overall AIH effect, as well as surgical, medical and AIH with delirium exposures were investigated. A novel approach was taken to include concurrent hospitalisation variables in the same model to allow effects to overlap, and use continuous variables to quantify effects accurately.The sample had a mean age of 78.8 years, a mean Mini-Mental State Examination score of 28.7 and was functionally independent. Over ten years, 82% were hospitalised with a mean of 1.7 medical and 1.6 surgical hospitalisations. Their mean global cognition z-score decline per year was -0.105. Recent AIH exposure was associated with an increased rate of decline (-0.014 ± 0.005 p = .008). AIH episodes had a greater association with cognitive decline than length of stay. This association was greater for medical admissions and especially so for AIH complicated

While the biological substrates of brain and behavioural changes in persons with schizophrenia remain unclear, increasing evidence implicates that inflammation is involved. In schizophrenia, including first-episode psychosis and anti-psychotic naive patients, there are numerous reports of increased peripheral inflammation, cognitive deficits and neuropathologies such as cortical thinning. Research defining the relationship between inflammation and schizophrenia symptomatology and neuropathology is needed. Therefore, we analysed the level of C-reactive protein (CRP), a peripheral inflammation marker, and its relationship with cognitive functioning in a cohort of 644 controls and 499 schizophrenia patients. In a subset of individuals who underwent MRI scanning (99 controls and 194 schizophrenia cases), we tested if serum CRP was associated with cortical thickness. CRP was significantly increased in schizophrenia patients compared to controls, co-varying for age, sex, overweight/obesity and diabetes (p < 0.006E-10). In schizophrenia, increased CRP was mildly associated with worse performance in attention, controlling for age, sex and education (R =- 0.15, p = 0.001). Further, increased CRP was associated with reduced cortical thickness in three regions related to attention: the caudal middle frontal, the pars opercularis and the posterior cingulate cortices, which remained significant after controlling for multiple comparisons (all p < 0.05). Together, these findings indicate that increased peripheral inflammation is associated with deficits in cognitive function and brain structure in schizophrenia, especially reduced attention and reduced cortical thickness in associated brain regions. Using CRP as a biomarker of peripheral inflammation in persons with schizophrenia may help to identify vulnerable patients and those that may benefit from adjunctive anti-inflammatory treatments.Copyright © 2021, Springer-Verlag GmbH, DE part of Springer Nature.

This study aimed to examine whether pulmonary function and cognition are independently associated at multiple time points. We included 8264 participants (49.9% women) aged 50-94 years at baseline from the China Health and Retirement Longitudinal Study in our analysis. Participants were enrolled in 2011 and followed up in 2013 and 2015. Cognitive function was assessed through a face-to-face interview in each survey. Pulmonary function was assessed via peak expiratory flow. Pulmonary function and cognitive function decreased significantly with age in both genders. Individuals in quintile 5 of pulmonary function had a relative increase in immediate memory (beta (95% CI): 0.19 (0.09, 0.30)) and delayed memory (0.16 (0.04, 0.28)) during follow-up compared with those in quintile 1. In the repeated-measures analysis, each standard deviation increment of pulmonary function was associated with a 0.44 (95% CI: 0.34, 0.53), 0.12 (0.09, 0.15), 0.12 (0.08, 0.16), 0.08 (0.06, 0.11), and 0.10 (0.07, 0.14) higher increase in global cognitive score, immediate memory, delayed memory, orientation and subtraction calculation, respectively. The inverse association between pulmonary function and cognitive decline during follow-up was more evident in women (P for interaction=0.0333), low educated individuals (P for interaction=0.0002), or never smokers (P for interaction=0.0412). In conclusion, higher baseline pulmonary function was independently associated with a lower rate of cognitive decline in older adults. The positive association between pulmonary function and cognition was stronger in women, lower educated individuals, or never smokers.Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

BACKGROUND: Cigarette smoking is associated with worse cognition and decreased cortical volume and thickness in healthy cohorts. Chronic cigarette smoking is prevalent in schizophrenia spectrum disorders (SSD), but the effects of smoking status on the brain and cognition in SSD are not clear. This study aimed to understand whether cognitive performance and brain morphology differed between smoking and non-smoking individuals with SSD compared to healthy controls. METHOD(S): Data were obtained from the Australian Schizophrenia Research Bank. Cognitive functioning was measured in 299 controls and 455 SSD patients. Cortical volume, thickness and surface area data were analysed from T1-weighted structural scans obtained in a subset of the sample (n = 82 controls, n = 201 SSD). Associations between smoking status (cigarette smoker/non-smoker), cognition and brain morphology were tested using analyses of covariance, including diagnosis as a moderator. RESULT(S): No smoking by diagnosis interactions were evident, and no significant differences were revealed between smokers and non-smokers across any of the variables measured, with the exception of a significantly thinner left posterior cingulate in smokers compared to non-smokers. Several main effects of smoking in the cognitive, volume and thickness analyses were initially significant but did not survive false discovery rate (FDR) correction. CONCLUSION(S): Despite the general absence of significant FDR-corrected findings, trend-level effects suggest the possibility that subtle smoking-related effects exist but were not uncovered due to low statistical power. An investigation of this topic is encouraged to confirm and expand on our findings.

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an “Eastern Slavic NBS hot spot.” The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reac

Metaphorically, the future can be perceived as approaching us (time-moving metaphor) or as being approached by us (ego-moving metaphor). Also, in line with findings that our eyes look more up when thinking about the future than the past, the future’s location can be conceptualized in upwards terms. Eye movements were recorded in 19 participants with PTSD and 20 healthy controls. Participants with PTSD showed downward and healthy controls upward eye movements while processing an ego/time-moving ambiguous phrase, suggesting a passive (time-moving) outlook toward the future. If replicated, our findings may have implications for the conceptualization and treatment of PTSD.

Background: Accumulating evidence suggests that prenatal chemical exposure triggers epigenetic modifications that could influence health outcomes later in life. In this study, we investigated whether DNA methylation (DNAm) levels at the glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B) gene underlies the association between prenatal exposure to an endocrine disrupting chemical (EDC), bisphenol F (BPF), and lower cognitive functions in 7-year-old children. Methods: Data from 799 children participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) pregnancy cohort was analyzed. Prenatal BPF exposure was assessed by measuring BPF levels in maternal urine. At age 7, DNAm of three CpG sites in a regulatory region of the GRIN2B gene was analyzed from buccal swabs using bisulfite-Pyrosequencing. Cognitive functions, including full-scale IQ and four subscales, were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Associations between prenatal BPF exposure and GRIN2B DNAm, as well as between GRIN2B DNAm and cognitive functions, were determined using regression models adjusted for potential confounders. Generalized structural equation models (gSEM) were used to evaluate if GRIN2B DNAm mediates the association between prenatal BPF exposure and cognitive functions at 7 years of age. Results: Prenatal BPF exposure was positively associated with GRIN2B DNAm levels at the third CpG site (CpG3), while CpG3 methylation was inversely associated with cognitive test scores. Mediation analyses showed that CpG3 methylation exerted 6–9% of the association between BPF exposure and full-scale IQ, as well as verbal comprehension and perceptual reasoning in boys, while not significant in girls. Conclusions: This study is the first to identify locus-specific DNAm as a mediating factor underlying an epidemiological association between prenatal EDC exposure and cognitive functions in childhood. It also confirms previous fin

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.

Background: There is a paucity of information on the role of microvascular and inflammatory biomarkers in cognitive dysfunction. Objective: This study sought to evaluate the relationships between established and a number of peripheral biomarkers on cognitive patterns in 108 older adults with memory complaints. Methods: Participants in the AIBL Active study aged 60 years and older with at least one vascular risk factor and memory complaints completed a neuropsychological test battery and provided cross-sectional health data. Linear regression models adjusted for covariates examined associations between cognitive performance and a panel of vascular risk factors (Framingham cardiovascular scores, hs-CRP, homocysteine, fasting glucose, LDL-cholesterol) and peripheral biomarkers (TNF-α, BDNF, VCAM-1, ICAM-1, PAI-1, CD40L). Results: Higher fasting glucose and homocysteine levels were independent factors associated with poorer performance in Trail Making Test (TMT) B (adjusted β = 0.40 ± 0.10 and 0.43 ± 0.09, respectively). Increasing homocysteine levels were weakly associated with poorer global cognition and delayed recall (adjusted β = 0.23 ± 0.10 and -0.20 ± 0.10 respectively). Increasing Framingham cardiovascular scores were related to poorer performance in TMT B (β = 0.42 ± 0.19). There was early evidence of associations between increasing plasma TNF-α and poorer TMT B (adjusted β = 0.21 ± 0.10) and between increasing BDNF and better global cognition (β = -0.20 ± 0.09). Conclusion: This study provides evidence to support the associations between vascular risk factors (Framingham scores, fasting glucose, and homocysteine) and poorer cognitive functions. Additionally, we measured several peripheral biomarkers to further investigate their associations with cognition. The relationship between TNF-α, BDNF, and cognitive performance in various domains may offer new insights into potential mechanisms in vascular cognitive impairment. © 2020 - IOS Press and the authors. All r

Genetic mutations in FUS, a DNA/RNA-binding protein, are associated with inherited forms of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A novel transgenic FUS[1-359]-tg mouse line recapitulates core hallmarks of human ALS in the spinal cord, including neuroinflammation and neurodegeneration, ensuing muscle atrophy and paralysis, as well as brain pathomorphological signs of FTLD. However, a question whether FUS[1-359]-tg mouse displays behavioural and brain pro-inflammatory changes characteristic for the FTLD syndrome was not addressed. Here, we studied emotional, social and cognitive behaviours, brain markers of inflammation and plasticity of pre-symptomatic FUS[1-359]-tg male mice, a potential FTLD model. These animals displayed aberrant behaviours and altered brain expression of inflammatory markers and related pathways that are reminiscent to the FTLD-like syndrome. FTLD-related behavioural and molecular Journal of Cellular and Molecular Medicine features were studied in the pre-symptomatic FUS[1-359]-tg mice that received standard or new ALS treatments, which have been reported to counteract the ALS-like syndrome in the mutants. We used anti-ALS drug riluzole (8 mg/kg/d), or anti-inflammatory drug, a selective blocker of cyclooxygenase-2 (celecoxib, 30 mg/kg/d) for 3 weeks, or a single intracerebroventricular (i.c.v.) infusion of human stem cells (Neuro-Cells, 500 000-CD34+), which showed anti-inflammatory properties. Signs of elevated anxiety, depressive-like behaviour, cognitive deficits and abnormal social behaviour were less marked in FUS-tg–treated animals. Applied treatments have normalized protein expression of interleukin-1β (IL-1β) in the prefrontal cortex and the hippocampus, and of Iba-1 and GSK-3β in the hippocampus. Thus, the pre-symptomatic FUS[1-359]-tg mice demonstrate FTLD-like abnormalities that are attenuated by standard and new ALS treatments, including Neuro-Cell preparation. © 2020 The Authors. Journal

Falls among older people with diabetes mellitus (DM) are a major health concern. Preventive measures can be implemented to reduce the likelihood of falls. The aim of this study was to determine the factors most strongly associated with falls in older people living with DM who receive at-home care support services. This will inform home-visiting nurses to prioritise falls prevention strategies in the care of clients who are at high risk of falls. A retrospective analysis of routinely collected data from a large not-for-profit community aged care service provider was undertaken. The sample comprised adults aged >=65 years residing in Victoria, Australia, with a recorded diagnosis of DM, and who received at least one episode of care by the aged care provider during July 1, 2014 and June 30, 2015. Self-reported data on falls in previous 6 months was obtained via the Comprehensive Health Assessment Tool (CHAT). Selection of factors associated with falls was guided by the Falls Risk for Older People in the Community (FROP-Com) assessment tool. For the study population, data for these factors were obtained from clients' self-reported CHAT data, and from International Classification of Disease codes obtained from medical records. Descriptive statistics were used to identify the demographic and clinical profile; logistic regression was used to assess the strength of association between various factors and the occurrence of a fall. Data were obtained for 1,574 older adults; overall prevalence of falls was 30.6% (n = 482). Significant factors displaying the highest odds of falling were gait issues (OR: 2.11, p = 0.002); needing help to walk (OR: 1.91, p = <0.001); and cognitive dysfunction (OR: 1.55, p = 0.001). Interpreted with caution, several factors contribute to an increased odds of falling in older people with DM. Home-visiting nurses are uniquely placed to introduce preventive interventions to reduce the likelihood of debilitating falls in this population.Copyright © 20

BACKGROUND: In schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain-cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness. METHOD(S): Age-related change in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 individuals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR. RESULT(S): Patients showed exaggerated age-related decline in brain structure, but not fluid reasoning compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients. CONCLUSION(S): In schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure - cognition outcomes in the extant literature.

Objective: Delirium is common in intensive care patients and is associated with short- and long-term adverse outcomes. We investigated the long-term risk of cognitive impairment and post-traumatic stress disorder (PTSD) in intensive care patients with and without delirium. Method(s): This is a prospective cohort study in ICUs in two Australian university-affiliated hospitals. Patients were eligible if they were older than 18 years, mechanically ventilated for more than 24 h and did not meet exclusion criteria. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Variables assessing cognitive function and PTSD symptoms were collected at ICU discharge, after 6 and 12 months: Mini-Mental State Examination, Telephone Interview for Cognitive Status, Impact of Events Scale-Revised and Informant Questionnaire for Cognitive Decline (caregiver). Result(s): 103 participants were included of which 36% developed delirium in ICU. Patients with delirium were sicker and had longer duration of mechanical ventilation and ICU length of stay. After 12 months, 41/60 (68.3%) evaluable patients were cognitively impaired, with 11.6% representing the presence of symptoms consistent with dementia. When evaluated by the patient's caregiver, the patient's cognitive function was found to be severely impaired in a larger proportion of patients (14/60, 23.3%). Delirium was associated with worse cognitive function at ICU discharge, but not with long-term cognitive function. IES-R scores, measuring PTSD symptoms, were significantly higher in patients who had delirium compared to patients without delirium. In regression analysis, delirium was independently associated with cognitive function at ICU discharge and PTSD symptoms at 12 months. Conclusion(s): Intensive care survivors have significant rates of long-term cognitive decline and PTSD symptoms. Delirium in ICU was independently associated with short-term but not long-term cognitive function, and with long-term P

Delirium, a syndrome characterized by an acute change in attention, awareness and cognition, is caused by a medical condition that cannot be better explained by a pre-existing neurocognitive disorder. Multiple predisposing factors (for example, pre-existing cognitive impairment) and precipitating factors (for example, urinary tract infection) for delirium have been described, with most patients having both types. Because multiple factors are implicated in the aetiology of delirium, there are likely several neurobiological processes that contribute to delirium pathogenesis, including neuroinflammation, brain vascular dysfunction, altered brain metabolism, neurotransmitter imbalance and impaired neuronal network connectivity. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) is the most commonly used diagnostic system upon which a reference standard diagnosis is made, although many other delirium screening tools have been developed given the impracticality of using the DSM-5 in many settings. Pharmacological treatments for delirium (such as antipsychotic drugs) are not effective, reflecting substantial gaps in our understanding of its pathophysiology. Currently, the best management strategies are multidomain interventions that focus on treating precipitating conditions, medication review, managing distress, mitigating complications and maintaining engagement to environmental issues. The effective implementation of delirium detection, treatment and prevention strategies remains a major challenge for health-care organizations globally.Copyright © 2020, Springer Nature Limited.

Background and objectives Older adults with cognitive impairment are vulnerable to frequent hospital admissions and emergency department presentations. The aim of this study was to use a codesign approach to develop MyCare Ageing, a programme that will train volunteers to provide psychosocial support to older people with dementia and/or delirium in hospital and at home when discharged from hospital. Setting Melbourne, Victoria, Australia. Research design This study adopts an action research methodology. We report on two co-design workshops with keystakeholders: Workshop 1: identification of components from three existing programmes to inform the development of the MyCare Ageing program logic and, Workshop 2: identification of implementation strategies. Participants The key stakeholders and workshop participants included clinicians (geriatricians, nurses and allied health), hospital staff (volunteer coordinators and hospital executives), Baptcare staff, a consumer, researchers and implementation experts and project staff. Results Workshop 1 identified the components from three existing programmes - the Volunteer Dementia and Delirium Care programme, Home-Start and MyCare for inclusion in MyCare Ageing. In workshop 2, the p implementation plan was developed taking into consideration hospital-specific processes, training and support needs of volunteers and safety and risk management processes. Discussion and conclusion The codesign process was successfully applied to develop the MyCare Ageing programme to provide volunteer support to patients with dementia and/or delirium in hospital and their transition home. MyCare Ageing is an innovative programme that meets an identified need from hospitals and consumers to support patients with dementia and/or delirium to improve psychosocial outcomes on discharge from hospital.Copyright © 2020 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Background:Themajority of older people who fall and present to EmergencyDepartments (EDs) are reported not to receive guideline level care to reduce future risk of falls. The aim of this randomized controlled trial was to evaluate whether RESPOND, a 6-month telephone-based patient-centred program had an effect on falls and fall injuries in older people presenting to ED after a fall. Method(s): 541 older fallers who presented to a WA or Victorian ED were recruited (inclusion criteria: discharged home <72 hours, could walk without hands-on assistance, use a telephone, and no cognitive impairment (MMSE>23). Intervention participants (n=263, mean age=73) received the RESPOND intervention, comprising (1) home-based risk assessment; (2) six months telephone-based education, coaching, goal setting and support for evidence-based risk factor management; and (3) linkages to existing services; while controls (n=260, mean age=73) received usual care. Primary outcomes were falls and fall injuries in the 12-month follow-up. Secondary outcomes included ED presentations, hospital admissions, fractures, death, falls risk, falls efficacy and quality of life. Result(s): Falls rate was significantly lower in the RESPOND group (incidence rate ratio 0.65 [95%CI 0.43-0.99]; p=0.042). Although there was no significant difference in fall injuries (p=0.374), the rate of fractures was significantly lower in the RESPOND group (p=0.03).There were no significant group differences in other secondary outcomes. Conclusion(s): The RESPOND falls prevention program reduced falls and fractures, in older people presenting to the ED with a fall. Key learnings for translation include: potential scalability and sustainability of a patient-centred and predominantly telephonebased program.

Objective To describe the perspectives on life participation by young adults with childhood-onset chronic kidney disease (CKD). Design Semi-structured interviews; thematic analysis. Setting Multiple centres across six countries (Australia, Canada, India, UK, USA and New Zealand). Participants Thirty young adults aged 18 to 35 years diagnosed with CKD during childhood. Results We identified six themes: struggling with daily restrictions (debilitating symptoms and side effects, giving up valued activities, impossible to attend school and work, trapped in a medicalised life, overprotected by adults and cautious to avoid health risks); lagging and falling behind (delayed independence, failing to keep up with peers and socially inept); defeated and hopeless (incapacitated by worry, an uncertain and bleak future, unworthy of relationships and low self-esteem and shame); reorienting plans and goals (focussing on the day-to-day, planning parenthood and forward and flexible planning); immersing oneself in normal activities (refusing to miss out, finding enjoyment, determined to do what peers do and being present at social events); and striving to reach potential and seizing opportunities (encouragement from others, motivated by the illness, establishing new career goals and grateful for opportunities). Conclusions Young adults encounter lifestyle limitations and missed school and social opportunities as a consequence of developing CKD during childhood and as a consequence lack confidence and social skills, are uncertain of the future, and feel vulnerable. Some re-adjust their goals and become more determined to participate in 'normal' activities to avoid missing out. Strategies are needed to improve life participation in young adult 'graduates' of childhood CKD and thereby strengthen their mental and social well-being and enhance their overall health.Copyright ©

Background: Postpartum weight retention is a significant contributor to obesity in women, adverse perinatal events in subsequent pregnancies, and chronic disease risk. Health literacy is known to impact health behaviors. The study aimed to identify the health literacy domains utilized in postpartum weight management interventions and to determine their impact on weight, diet and physical activity in postpartum women. Method(s): We searched MEDLINE, CINAHL, EMBASE, PSYCINFO, and EBM databases. We included random control trials of lifestyle intervention in postpartum women (within two years post-delivery) published up to 3 May 2019. Subgroup analyses were performed to determine the effect of health literacy domains on outcomes. Result(s): Out of 5000 studies, 33 studies (n = 3905) were included in the systematic review and meta-analysis. The health literacy domain self-care (skills and knowledge) was associated with a significant reduction in body weight (mean difference (MD) -2.46 kg; 95% confidence interval (CI) from -3.65 to -1.27) and increase in physical activity (standardized mean difference (SMD) 0.61; 95% CI 0.20 to 1.02). No other health literacy domain was associated with significant outcomes in weight, energy intake, or physical activity. Conclusion(s): Health literacy skills such as knowledge of self-care are effective in improving weight and in increasing physical activity in postpartum women. The efficacy of other health domains was not supported.Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Serum alkaline phosphatase (ALP) is associated with incident cardiovascular disease (CVD), coronary artery disease, vascular calcification, cerebral small vessel disease and ischemic stroke. Recent studies also associate elevated ALP with impaired cognition, suggesting neuronal or neurovascular dysfunction. To date there is no specific pharmacological means to lower ALP. Bromodomain & extraterminal (BET) proteins bind to acetylated histones on chromatin and regulate gene transcription. Apabetalone (ABET) targets the second bromodomain of BET proteins and inhibits expression of genes that participate in vascular inflammation and calcification, coagulation and the complement pathway. In CVD patients (pts), ABET lowers serum ALP in a dose-dependent manner. Method(s): In phase 2 ABET studies (n=795) up to 26 weeks' duration in CVD pts, we assessed the relationship of ALP and CVD events. In the ongoing phase 3 BETonMACE study with ABET (n=2,425), baseline cognitive function (Montreal Cognitive Assessment, MoCA) and ALP were measured in pts aged 70 yrs and older (n=467). Result(s): In phase 2 studies, CVD events (death, non-fatal MI, coronary revascularization, or hospitalization for CV cause) were lowered by 44% (p=0.02) with ABET. Baseline ALP (median 72 U/L) independently predicted CVD events (hazard ratio [HR] per standard deviation [SD] 1.6, 95% CI 1.2-2.1, p<0.001). Mean ABET decrease in ALP from baseline was 8.45% (p<0.001), or 6.6 U/L. A 1 SD (13.0 U/L) reduction in ALP with ABET was associated with a HR for MACE of 0.58 (95% CI 0.43-0.78, p<0.001). In the BETonMACE trial pts were classified by baseline MoCA >26 (normal, n=221), 21-25 (borderline, n=161), or <21 (impaired, n=85). Pts with impaired cognition had higher ALP (trend p-value 0.006), lower eGFR (66 vs. 71, p=0.04), and higher hsCRP (4.8 vs.1.8, p=0.03). Conclusion(s): Serum ALP is associated with coronary and cerebral vascular disease. ABET is a BET-inhibitor that lowers serum ALP in CVD pts

Childhood adversity, such as physical, sexual, and verbal abuse, as well as neglect and family conflict, is a risk factor for schizophrenia. Such adversity can lead to disruptions of cognitive function during development, undermining intellectual capabilities and academic achievement. Schizophrenia is a neurodevelopmental disorder that is associated with cognitive impairments that may become evident during childhood. The Australian Schizophrenia Research Bank database comprises a large community cohort (N = 1169) in which we previously identified 3 distinct cognitive groups among people with schizophrenia: (1) Compromised, current, and estimated premorbid cognitive impairment; (2) Deteriorated, substantial decline from estimated premorbid function; and (3) Preserved, performing in the normal cognitive range without decline. The compromised group displayed the worst functional and symptom outcomes. Here, we extend our previous work by assessing the relationship among these categories of cognitive abilities and reported childhood adversity in 836 patients and healthy controls. Exploratory factor analysis of the Childhood Adversity Questionnaire revealed 3 factors (lack of parental involvement; overt abuse; family breakdown and hardship). People with schizophrenia reported significantly more childhood adversity than healthy controls on all items and factors. People with schizophrenia in the compromised group reported significantly more lack of parental involvement and family breakdown and hardship and lower socioeconomic status than those in the deteriorated group. The cognitive groups were not related to family history of psychosis. These findings identify specific social and family factors that impact cognition, highlighting the important role of these factors in the development of cognitive and functional abilities in schizophrenia.Copyright © 2019 Crown copyright 2019.