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To study the outcome of delirium in elderly hip surgery patients. Prospective matched controlled cohort study. Hip surgery patients (n = 112) aged 70 years and older, who participated in a controlled clinical trial of haloperidol prophylaxis for delirium, were followed for an average of 30 months after discharge. Patients with a diagnosis of dementia or mild cognitive impairment (MCI) were identified using psychiatric interviews. Proportions of patients with dementia/MCI were compared across patients who had postoperative delirium and selected control patients matched for preoperatively assessed risk factors who had not developed delirium during index hospitalization. Other outcomes were mortality rate and rate of institutionalization. During the follow-up period, 54.9% of delirium patients had died compared to 34.1% of the controls (relative risk = 1.6, 95% CI = 1.0-2.6). Dementia or MCI was diagnosed in 77.8% of the surviving patients with postoperative delirium and in 40.9% of control patients (relative risk = 1.9, 95% CI = 1.1-3.3). Half of the patients with delirium were institutionalized at follow-up compared to 28.6% of the controls (relative risk = 1.8, 95% CI = 0.9-3.4). The risk of dementia or MCI at follow-up is almost doubled in elderly hip surgery patients with postoperative delirium compared with at-risk patients without delirium. Delirium may indicate underlying dementia.

Objectives were to develop a frailty index (FI) based on a standard comprehensive geriatric assessment (CGA) derived from a clinical examination; to assess the validity of the FI-CGA and to compare its precision with other frailty measures. Secondary analysis of a prospective cohort study, with five-year follow-up data. Second phase of the Canadian Study of Health and Aging (CSHA-2); clinical examinations were performed in clinics, nursing homes, and patients' homes. People selected (as either cognitively impaired cases or unimpaired controls) to receive the CSHA-2 clinical examination (n = 2305; women = 1431). Clinical and performance-based measures and diagnostic data were extracted to correspond to the 10 impairment domains and the single comorbidity domain of a CGA. The proportion of deficits accumulated in each domain was calculated to yield the FI-CGA. The FI-CGA was validated and its predictive ability compared with other frailty measures. Within the seven grades of fitness/frailty identified, subjects with greater frailty were older, less educated, and more likely to be women. The FI-CGA correlated highly with a previously validated, empirically-derived frailty index (r = 0.76). Frailty was associated with higher risk of death (for each increment in frailty, the hazard ratio, adjusted for age, sex and education, was 1.23 (95% CI 1.18-1.29) and institutionalization (HR 1.20; 1.10-1.32). In a population survey, the FI-CGA is a valid means of quantifying frailty from routinely collected data.

Objectives To determine the relation between delirium in critically ill patients and their outcomes in the short term (in the intensive care unit and in hospital) and after discharge from hospital.Design Systematic review and meta-analysis of published studies.Data sources PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 January 2015.Eligibility criteria for selection studies Reports were eligible for inclusion if they were prospective observational cohorts or clinical trials of adults in intensive care units who were assessed with a validated delirium screening or rating system, and if the association was measured between delirium and at least one of four clinical endpoints (death during admission, length of stay, duration of mechanical ventilation, and any outcome after hospital discharge). Studies were excluded if they primarily enrolled patients with a neurological disorder or patients admitted to intensive care after cardiac surgery or organ/tissue transplantation, or centered on sedation management or alcohol or substance withdrawal. Data were extracted on characteristics of studies, populations sampled, identification of delirium, and outcomes. Random effects models and meta-regression analyses were used to pool data from individual studies.Results Delirium was identified in 5280 of 16 595 (31.8%) critically ill patients reported in 42 studies. When compared with control patients without delirium, patients with delirium had significantly higher mortality during admission (risk ratio 2.19, 94% confidence interval 1.78 to 2.70; P<0.001) as well as longer durations of mechanical ventilation and lengths of stay in the intensive care unit and in hospital (standard mean differences 1.79 (95% confidence interval 0.31 to 3.27; P<0.001), 1.38 (0.99 to 1.77; P<0.001), and 0.97 (0.61 to 1.33; P<0.001), respectively). Available studies indicated an association between delirium and cognitive impairment after discharge.Conclusions Nearly a third of patients admitted to an intensive care unit develop delirium, and these patients are at increased risk of dying during admission, longer stays in hospital, and cognitive impairment after discharge.

Background The sequelae of sepsis were once thought to be independent of sepsis itself and assumed to be either comorbid to sick patients or complications of critical illness. Recent studies have reported consistent patterns of functional disabilities in sepsis survivors that can last from months to years after symptoms of active sepsis had resolved. Body Post-sepsis syndrome is an emerging pathological entity that has garnered significant interest amongst clinicians and researchers over the last two decades. It is marked by a significantly increased risk of death and a poor health-related quality of life associated with a constellation of long-term effects that persist following the patient’s bout with sepsis. These include neurocognitive impairment, functional disability, psychological deficits, and worsening medical conditions. Conclusion This “post-sepsis syndrome” has been the subject of active preclinical and clinical research providing new mechanistic insights and approaches linked to survivor well-being. Here we review important aspects of these research efforts and goals of care for patients who survive sepsis.

ObjectiveTo investigate whether concomitant Alzheimer's disease (AD) pathology, reflected by cerebrospinal fluid (CSF) biomarkers, has an impact on dementia with Lewy bodies (DLB) in terms of clinical presentation, cognitive decline, nursing home admittance and survival.ParticipantsWe selected 111 patients with probable DLB and CSF available from the Amsterdam Dementia Cohort. On the basis of the AD biomarker profile (CSF tau/amyloid-β 1–42 (Aβ42) ratio >0.52), we divided patients into a DLB/AD+ and DLB/AD– group. Of the 111 patients, 42 (38%) had an AD CSF biomarker profile. We investigated differences between groups in memory, attention, executive functions, language and visuospatial functions. Difference in global cognitive decline (repeated Mini-Mental State Examination (MMSE)) was investigated using linear mixed models. Cox proportional hazard analyses were used to investigate the effects of the AD biomarker profile on time to nursing home admittance and time to death.ResultsMemory performance was worse in DLB/AD+ patients compared with DLB/AD− patients (p<0.01), also after correction for age and sex. Hallucinations were more frequent in DLB/AD+ (OR=3.34, 95% CI 1.22–9.18). There was no significant difference in the rate of cognitive decline. DLB/AD+ patients had a higher mortality risk (HR=3.13, 95% CI 1.57 to 6.24) and nursing home admittance risk (HR=11.70, 95% CI 3.74 to 36.55) compared with DLB/AD− patients.ConclusionsDLB-patients with a CSF AD profile have a more severe manifestation of the disease and a higher risk of institutionalisation and mortality. In clinical practice, CSF biomarkers may aid in predicting prognosis in DLB. In addition, DLB-patients with positive AD biomarkers could benefit from future treatment targeting AD pathology.

We present a simple and efficient hypothesis-free machine learning pipeline for risk factor discovery that accounts for non-linearity and interaction in large biomedical databases with minimal variable pre-processing. In this study, mortality models were built using gradient boosting decision trees (GBDT) and important predictors were identified using a Shapley values-based feature attribution method, SHAP values. Cox models controlled for false discovery rate were used for confounder adjustment, interpretability, and further validation. The pipeline was tested using information from 502,506 UK Biobank participants, aged 37–73 years at recruitment and followed over seven years for mortality registrations. From the 11,639 predictors included in GBDT, 193 potential risk factors had SHAP values ≥ 0.05, passed the correlation test, and were selected for further modelling. Of the total variable importance summed up, 60% was directly health related, and baseline characteristics, sociodemographics, and lifestyle factors each contributed about 10%. Cox models adjusted for baseline characteristics, showed evidence for an association with mortality for 166 out of the 193 predictors. These included mostly well-known risk factors (e.g., age, sex, ethnicity, education, material deprivation, smoking, physical activity, self-rated health, BMI, and many disease outcomes). For 19 predictors we saw evidence for an association in the unadjusted but not adjusted analyses, suggesting bias by confounding. Our GBDT-SHAP pipeline was able to identify relevant predictors ‘hidden’ within thousands of variables, providing an efficient and pragmatic solution for the first stage of hypothesis free risk factor identification.

Results of the few cohort studies from countries with low incomes or middle incomes suggest a lower incidence of dementia than in high-income countries. We assessed incidence of dementia according to criteria from the 10/66 Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders (DSM) IV, the effect of dementia at baseline on mortality, and the independent effects of age, sex, socioeconomic position, and indicators of cognitive reserve. We did a population-based cohort study of all people aged 65 years and older living in urban sites in Cuba, the Dominican Republic, and Venezuela, and rural and urban sites in Peru, Mexico, and China, with ascertainment of incident 10/66 and DSM-IV dementia 3–5 years after cohort inception. We used questionnaires to obtain information about age in years, sex, educational level, literacy, occupational attainment, and number of household assets. We obtained information about mortality from all sites. For participants who had died, we interviewed a friend or relative to ascertain the likelihood that they had dementia before death. 12 887 participants were interviewed at baseline. 11 718 were free of dementia, of whom 8137 (69%) were reinterviewed, contributing 34 718 person-years of follow-up. Incidence for 10/66 dementia varied between 18·2 and 30·4 per 1000 person-years, and were 1·4–2·7 times higher than were those for DSM-IV dementia (9·9–15·7 per 1000 person-years). Mortality hazards were 1·56–5·69 times higher in individuals with dementia at baseline than in those who were dementia-free. Informant reports suggested a high incidence of dementia before death; overall incidence might be 4–19% higher if these data were included. 10/66 dementia incidence was independently associated with increased age (HR 1·67; 95% CI 1·56–1·79), female sex (0·72; 0·61–0·84), and low education (0·89; 0·81–0·97), but not with occupational attainment (1·04; 0·95–1·13). Our results provide supportive evidence for the cognitive reserve hypothesis, showing that in middle-income countries as in high-income countries, education, literacy, verbal fluency, and motor sequencing confer substantial protection against the onset of dementia. Wellcome Trust Health Consequences of Population Change Programme, WHO, US Alzheimer's Association, FONACIT/ CDCH/ UCV

Despite several studies demonstrating an independent and inverse association between cognition and mortality, the nature of this association still remains unclear. To examine the association of cognition and mortality after accounting for sociodemographic, health and lifestyle factors and to explore both test and population characteristics influencing this relationship. In a population based cohort of 8585 men and women aged 48-92 years, who had cognitive assessments in 2006-2011 and were followed up till 2016 for mortality, we examined the relationship between individual cognitive tests as well as a global cognition score to compare their ability in predicting mortality and whether these differed by population characteristics. Risk of death was estimated using Cox proportional hazard regression models including sociodemographic, lifestyle and health variables, and self-reported comorbidities, as covariates in the models. Poor cognitive performance (bottom quartile of combined cognition score) was associated with higher risk of mortality, Hazard Ratio = 1.32 (95% Confidence Interval 1.09, 1.60); individual cognitive tests varied in their mortality associations and also performed differently in middle-age and older age groups. Poor cognitive performance is independently associated with higher mortality. This association is observed for global cognition and for specific cognitive abilities. Associations vary depending on the cognitive test (and domain) as well as population characteristics, namely age and education.

ObjectiveHistorical cohort studies have reported adverse neurodevelopment following cardiac surgery during early infancy. Advances in surgical techniques and perioperative care have coincided with updating of neurodevelopmental assessment tools. We aimed to determine perioperative risk factors for impaired neurodevelopment at 2 years following surgery for congenital heart disease (CHD) in early infancy.Design and patientsWe undertook a prospective longitudinal study of 153 full-term infants undergoing surgery for CHD before 2 months of age. Infants were excluded if they had a genetic syndrome associated with neurodevelopmental impairment.Outcome measuresPredefined perioperative parameters were recorded and infants were classified according to cardiac anatomy. At 2 years, survivors were assessed using the Bayley Scales of Infant Development-III.ResultsAt 2 years, 130 children (98% of survivors) were assessed. Mean cognitive, language and motor scores were 93.4±13.6, 93.6±16.1 and 96.8±12.5 respectively (100±15 norm). Twenty (13%) died and 12 (9%) survivors had severe impairment (score <70), mostly language (8%). The lowest scores were in infants born with single ventricle physiology with obstruction to the pulmonary circulation who required a neonatal systemic-to-pulmonary artery shunt. Additional risk factors for impairment included reduced gestational age, postoperative elevation of lactate or S100B and repeat cardiac surgery.ConclusionsIn the modern era of infant cardiac surgery and perioperative care, children continue to demonstrate neurodevelopmental delays. The use of updated assessment tools has revealed early language dysfunction and relative sparing of motor function. Ongoing follow-up is critical in this high-risk population.

Background Significant heterogeneity in clinical features of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) cases with the pathogenic C9orf72 expansion (C9P) have been described. To clarify this issue, we compared a large C9P cohort with carefully matched non-expansion (C9N) cases with a known or highly-suspected underlying TAR DNA-binding protein 43 (TDP-43) proteinopathy. Methods A retrospective case-control study was carried out using available cross-sectional and longitudinal clinical and neuropsychological data, MRI voxel-based morphometry (VBM) and neuropathological assessment from 64 C9P cases (ALS=31, FTLD=33) and 79 C9N cases (ALS=36, FTLD=43). Results C9P cases had an earlier age of onset (p=0.047) and, in the subset of patients who were deceased, an earlier age of death (p=0.014) than C9N. C9P had more rapid progression than C9N: C9P ALS cases had a shortened survival (2.6±0.3 years) compared to C9N ALS (3.8±0.4 years; log-rank λ2=4.183, p=0.041), and C9P FTLD showed a significantly greater annualised rate of decline in letter fluency (4.5±1.3 words/year) than C9N FTLD (1.4±0.8 words/year, p=0.023). VBM revealed greater atrophy in the right frontoinsular, thalamus, cerebellum and bilateral parietal regions for C9P FTLD relative to C9N FTLD, and regression analysis related verbal fluency scores to atrophy in frontal and parietal regions. Neuropathological analysis found greater neuronal loss in the mid-frontal cortex in C9P FTLD, and mid-frontal cortex TDP-43 inclusion severity correlated with poor letter fluency performance. Conclusions C9P cases may have a shorter survival in ALS and more rapid rate of cognitive decline related to frontal and parietal disease in FTLD. C9orf72 genotyping may provide useful prognostic and diagnostic clinical information for patients with ALS and FTLD.