OBJECTIVEPeople with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Hypoglycemia is a candidate risk factor, but the direction of association between episodes of severe hypoglycemia and cognitive decline in type 2 diabetes remains uncertain. RESEARCH DESIGN AND METHODSIn the Edinburgh Type 2 Diabetes Study, cognitive function was assessed in 831 adults with type 2 diabetes (aged 60-75 years) at baseline and after 4 years. Scores on seven neuropsychological tests were combined into a standardized general ability factor g. Self-reported history of severe hypoglycemia at baseline (history of hypoglycemia) and at follow-up (incident hypoglycemia) was recorded. RESULTSA history of hypoglycemia was reported by 9.3% of subjects, and 10.2% reported incident hypoglycemia. Incident hypoglycemia was associated with poorer cognitive ability at baseline (age-and sex-adjusted odds ratio for lowest tertile of g 2.04 [95% CI 1.25-3.31], P = 0.004). Both history of hypoglycemia and incident hypoglycemia were also associated with greater cognitive decline during followup (mean follow-up g adjusted for age, sex, and baseline g 20. CONCLUSIONSThe relationship between cognitive impairment and hypoglycemia appeared complex, with severe hypoglycemia associated with both poorer initial cognitive ability and accelerated cognitive decline. Diabetes Care 2014;37:507-515 | DOI: 10.233737:507-515 | DOI: 10. /dc13-1384 Type 2 diabetes is associated with an increased risk of cognitive impairment, agerelated cognitive decline, and dementia (1). Given the increasing numbers of elderly people with type 2 diabetes in the general population, the identification of potentially modifiable risk factors and the prevention of cognitive decline during older age in this group are of major importance to public health. Although the

Older people with type 2 diabetes are at increased risk of developing cognitive impairment, for which several potential risk factors have been proposed. The present article reviews evidence in people with type 2 diabetes for associations of cognitive impairment with a range of vascular, metabolic, and psychosocial risk factors, many of which have a higher prevalence in people with type 2 diabetes than in non-diabetic adults of a similar age. Definitive research studies in this field are few in number. The risk factors may be involved in causal pathways or may act as useful markers of cerebrovascular damage (or both), and for which relatively consistent evidence is available, include poor glycemic control, hypoglycemia, microvascular disease, inflammation, and depression. For macrovascular disease, the strength of the association with cognitive impairment appears to depend on which vascular system has been examined. A role for pre-morbid ability in young adulthood as influencing the risk of both diabetes and cognitive impairment has also been suggested. The importance of considering inter-relationships between risk factors when investigating their potential contribution to cognitive impairment in future investigations is discussed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-015-0130-5) contains supplementary material, which is available to authorized users.

Patients with a relatively higher level of education are at reduced risk of POCD. Risk stratification of surgical patients according to educational level may prove useful.

Patients with diabetes appear to have a higher risk of POCD compared with diabetes-free persons. Among patients with diabetes, POCD risk may further increase with poorer glycemic control as indexed by higher HbA1c. The roles of HbA1c levels among nondiabetic persons in POCD risk warrant further research.

OBJECTIVEMacrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes. We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes.RESEARCH DESIGN AND METHODSEight hundred thirty-one men and women (aged 60–75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS). At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP). Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g). Adjustment of follow-up g for baseline g assessed 4-year cognitive change. Adjustment for vocabulary (estimated premorbid ability) was used to estimate lifetime cognitive change.RESULTSMeasures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. The association of stroke with increased estimated lifetime cognitive decline (standardized β, −0.12) and of subclinical markers with actual 4-year decline (standardized β, −0.12, 0.12, and −0.15 for NT-proBNP, ABI, and cIMT, respectively) reached the Bonferroni-adjusted level of statistical significance (P < 0.006). Results altered only slightly on adjustment for vascular risk factors.CONCLUSIONSStroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes. Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted.

Background The metabolic syndrome (MetS) is an established cardiovascular risk factor. Here, we investigated its role in cognitive impairment. Methods Baseline data from 202 participants (aged 65 to 87 years) of the BioCog study were used. All were free of clinical dementia (MMSE≥24/30). Cognitive impairment was defined as the lowest tertile of a cognitive summary score. Multiple logistic regression analyses examined associations of body mass index (BMI), triglycerides (TG), high-density lipoprotein (HDL-C), glucose and glycated hemoglobin A1c (HbA1c) levels with the odds of cognitive impairment. MetS was defined as ≥3 of its 5 components obesity (BMI ≥ 30 kg/m 2 ), elevated TG (TG ≥1.7 mmol/L), reduced HDL-C (males: < 1.0 mmol/L; females: < 1.3 mmol/L), elevated glucose (glucose ≥5.5 mmol/L and/or diagnosed diabetes) and elevated blood pressure (history of hypertension). Analyses controlled for age, sex and smoking history. Results Lower HDL-C was significantly associated with a higher odds of cognitive impairment (OR 2.70 per 1 mmol/L reduction; 95% CI 1.25, 5.56; p = 0.011), whereas BMI, TG, glucose and HbA1c were not (all p > 0.05). Results for HDL-C were similar when HDL-C, glucose, BMI and TG were entered into a single model (OR 2.56 per 1 mmol/L reduction, 95% CI 1.09, 5.88, p = 0.031) and when cerebrovascular disease and coronary heart disease were additionally controlled for (OR 2.56 per 1 mmol/L reduction, 95% CI 1.06, 6.25, p = 0.036). Among the 5 MetS components, participants with elevated TG were at 2-fold increased odds of impairment (OR 2.09, 95% CI 1.08, 4.05, p = 0.028) including when the remaining 4 MetS components were entered (OR 2.23, 95% CI 1.07, 4.65, p = 0.033), but the finding was no longer statistically significant when cerebrovascular disease and coronary heart disease were additionally controlled for ( p = 0.11). Presence of MetS and of obesity, reduced HDL-C, elevated glucose or elevated blood pressure were not significantly associated with impairment (all p > 0.05). Conclusion Our findings support low HDL-C as an independent risk marker of cognitive impairment in older age. The need for research into mediatory and confounding factors, and re-evaluation of traditional cut-off points is highlighted. Trial registration The study was registered on 15th October 2014 at clinicaltrials.gov ( NCT02265263 ).

Obesity and post-operative cognitive dysfunction: a systematic review and meta-analysis Feinkohl, I. and Winterer, G. and Pischon, T. This is the final version of the manuscript. It is the peer reviewed version of the following article: Email: insa.feinkohl@mdc-berlin.de Abstract Background Post-operative cognitive dysfunction (POCD) occurs frequently after surgery, and is related to dementia and premature death. Obesity increases the risk of late-life cognitive impairment, but little is known about its role in POCD. We conducted a systematic review and metaanalysis of studies on the association between obesity and risk of POCD. Methods PubMed and the Cochrane Library were systematically searched. Studies were included if they had prospective designs, reported on human adults undergoing surgery, if cognitive function was measured pre-and post-surgery, if obesity, body mass index (BMI) and/or body weight were ascertained, and if associations with POCD were reported as relative risks or odds ratios. Underweight, weight loss, and post-operative delirium were not considered. Results Inclusion criteria were met by six articles. Samples totaled 1432 older patients (mean age ≥62 years) who were followed up for 24 hours to twelve months after surgery. Analysis of studies with obesity defined as a categorical measure found a non-significantly higher risk of POCD among persons with BMI>30 kg/m 2 versus ≤30 kg/m 2 (RR 1.27; 95% CI 0.95, 1.70; p=0.10). No such associations were found for studies that analyzed BMI or body weight continuously as predictors of POCD (RR 0.98 per kg/m 2 ; 95% CI 0.93, 1.03, p=0.45; RR 0.99 per kg; 95% CI 0.89, 1.09; p=0.83, respectively). Conclusions Few studies have addressed the topic, and the results of these studies provide only limited support for an increased risk of POCD in patients who are obese. Further large-scale, prospective investigations are necessary for clarification.Keywords: obesity, body weight, adiposity, post-operative cognitive dysfunction, POCD. Table): 3129 Introduction Post-operative cognitive dysfunction (POCD) is a frequent condition that may occur after any type of surgery. POCD broadly refers to a "deterioration in cognition temporally associated with surgery" [1]. In contrast to post-operative delirium (POD), POCD is characterized by intact consciousness and a more subtle onset [2], and it is thought to be caused by distinct pathology. POCD is considered as a transient condition [3], but disease progression and resulting cognitive trajectories of POCD vary substantially between individuals [4] and depend on the time since surgery. Overall incidence rates in older age groups range between 10-38% [5][6][7][8] within the first 2 to 3 months and 3-24% at 6 to 12 months after surgery [7,9,10]. Further, POCD appears to increase the risk of subsequent dementia diagnosis as well as premature death [3,6,11,12]. The etiology and pathophysiology of POCD are relatively unclear, and only a few risk factors have been identified to date, including higher age and preexisting cog...

Objectives: Hemophagocytic lymphohistiocytosis is a cytokine release syndrome caused by uncontrolled immune activation resulting in multiple organ failure and death. In this systematic review, we aimed to analyze triggers, various treatment modalities, and mortality in critically ill adult hemophagocytic lymphohistiocytosis patients. Data Sources: MEDLINE database (PubMed) at October 20, 2019. Study Selection: Studies and case series of patients greater than or equal to 18 years old, of whom at least one had to be diagnosed with hemophagocytic lymphohistiocytosis and admitted to an ICU. Data Extraction: Source data of studies and case series were summarized and analyzed on an individual basis. Multivariable logistic regression analysis was performed adjusting for age, sex, and trigger groups. Each single treatment agent was entered as a dichotomous variable to determine treatments associated with survival, regardless if given alone or in combination. Data Synthesis: In total, 661 patients from 65 studies and case series were included. Overall mortality was 57.8%. Infections were the most frequent trigger (49.9%), followed by malignancies (28.0%), autoimmune diseases (12.1%), unknown triggers (9.4%), and drugs (0.6%). Treatment with IV immunoglobulins was associated with improved survival (odds ratio, 0.548; 95% CI, 0.337–0.891; p = 0.015), while treatment with cyclosporine was associated with increased risk of death (odds ratio, 7.571; 95% CI, 3.702–15.483; p < 0.001). Considering different trigger groups separately, same results occurred only for infection-triggered hemophagocytic lymphohistiocytosis. No information was available on disease severity and other confounding factors. Conclusions: Mortality of hemophagocytic lymphohistiocytosis in the ICU is high. Most common triggers were infections. Results of survival analyses may be biased by treatment indication and disease severity. Future studies prospectively investigating treatment tailored to critically ill hemophagocytic lymphohistiocytosis patients are highly warranted.