Plasma leptin, but not adiponectin, is associated with cognitive impairment in older adults

BACKGROUND: Leptin and adiponectin are adipose-tissue derived hormones primarily involved in glucose, lipid, and energy metabolism, inflammation, and atherosclerosis. Both adipokines may cross the blood-brain barrier but evidence on their roles in cognitive impairment is limited and conflicting. Here, we determined associations of plasma adipokine concentration with cognitive impairment in older adults. METHODS: Cross-sectional analysis of baseline data from 669 participants aged ≥65 years of the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study were recruited 2014–2017 at study sites in Berlin, Germany and Utrecht, the Netherlands. Cognitive impairment was defined as the lowest tertile of a cognitive summary score derived from six neuropsychological tests. RESULTS: After adjustment for age, sex, fasting, BMI, diabetes, hypertension, cerebrovascular disease, and coronary heart disease, higher leptin concentrations and a higher leptin/adiponectin ratio (LAR) were associated with a higher odds of cognitive impairment (OR per 1 SD higher leptin concentration, 1.33; 95 % CI 1.05, 1.69; p = 0.02; OR per 1 SD higher LAR, 1.26; 95 % CI 1.01, 1.57; p = 0.04). Sensitivity analyses determined that these findings were driven by the non-obese group (BMI < 30 kg/m2), whereas leptin and LAR were not associated with cognitive impairment in the obese group (BMI ≥ 30 kg/m2). Soluble leptin receptor, leptin/soluble leptin receptor ratio, total adiponectin and high-molecular weight adiponectin concentrations were each not associated with impairment. CONCLUSIONS: With leptin as a known promoter of atherosclerosis and inflammation, our findings point to a pathogenic role of leptin in age-related cognitive impairment that may be limited to non-obese individuals and warrants further investigation

Associations of the metabolic syndrome and its components with cognitive impairment in older adults

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/m2), elevated TG (TG ≥1.7 mmol/L), reduced HDL-C (males:  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)

Prospectively measured lifestyle factors and BMI explain differences in health-related quality of life between colorectal cancer patients with and without comorbid diabetes

Purpose This study aimed to assess the longitudinal association between lifestyle factors, body mass index (BMI), and health-related quality of life (HRQoL) among colorectal cancer patients with (CRCDM+) and without diabetes (CRCDM−). Methods Data from a longitudinal study among CRC patients diagnosed between 2000 and 2009 were used. Clinical characteristics were retrieved from the Netherlands Cancer Registry and questionnaires were sent in 2010, 2011, and 2012 using the Patient Reported Outcomes Following Initial Treatment and Long term Evaluation of Survivorship (PROFILES) registry. Lifestyle (including moderate-to-vigorous physical activity (MVPA), smoking and alcohol use), BMI, diabetes status, and HRQoL were assessed in the questionnaire. Results One thousand seven hundred thirty-nine (49 %) patients responded to ≥2 questionnaires, of whom 126 CRCDM+ and 789 CRCDM− patients were included. CRCDM+ patients had a higher BMI (29.1 ± 4.2 vs. 26.4 ± 3.7 kg/m2), whereas the number of alcohol users was lower (50 vs. 70 %, p value <0.0001) among CRCDM+ as compared to CRCDM− patients. Analyses adjusted for sociodemographic and cancer characteristics showed that CRCDM+ patients reported statistically significantly lower physical function (beta = -5.76; SE = 1.67), global QoL (beta = -4.31; SE = 1.48), and more symptoms of fatigue (beta = 5.38; SE = 1.95) than CRCDM− patients. However, these effects disappeared after adjustments for lifestyle factors and BMI which were all significant predictors of HRQoL. Additional adjustment for comorbidity further attenuated the main effect of DM on HRQoL. Conclusions Diabetes was not independently associated with HRQoL but deteriorated HRQoL among CRCDM+ patients seem to be explained by an unhealthier lifestyle and other comorbid conditions. Moreover, residual confounding cannot be ruled out.KeywordsColorectal cancer, Diabetes, Lifestyle, Health-related quality of lif

The association between frailty and MRI features of cerebral small vessel disease

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

Metabolic syndrome and the risk of postoperative delirium and postoperative cognitive dysfunction: a multi-centre cohort study

BACKGROUND: Metabolic syndrome and its components are risk factors for cognitive impairment, but their contribution to perioperative neurocognitive disorders is unknown. We examined their associations with the risk of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in older patients. METHODS: In 765 male and female participants aged =65 years, we measured preoperative metabolic parameters and screened for POD for 7 days or until discharge. POCD was defined through comparison of cognitive change on six neuropsychological tests with non-surgical controls. Multiple logistic regression analyses examined the association of metabolic parameters with risk of POD and POCD with adjustment for age, sex, and surgery type. RESULTS: A total of 149 patients (19.5% of 765) developed POD and 53 (10.1% of 520 attendees) had POCD at 3 months. Patients with metabolic syndrome were at 1.85-fold higher risk of POD (95% confidence interval [CI] 1.26-2.70). Each 1 mmol L(-1) higher high-density lipoprotein cholesterol (HDL-C) was associated with a 0.47-fold lower POD risk (95% CI 0.30-0.74). Each 1 kg m(-2) higher body mass index (BMI) was associated with a 1.09-fold higher POCD risk (95% CI 1.02- 1.16). CONCLUSIONS: Older surgical patients with metabolic syndrome were at increased risk of POD. Only reduced HDL-C was significantly associated with POD. For POCD, a higher preoperative BMI was identified as a risk factor. These findings add to mounting evidence of a distinct epidemiology of POD and POCD. Screening programmes taking advantage of HDL-C and BMI measurements and of metabolic interventions in reducing perioperative neurocognitive disorders should be evaluated

Basal forebrain cholinergic system volume is associated with general cognitive ability in the elderly

OBJECTIVE: At the present, it is unclear whether association of basal forebrain cholinergic system (BFCS) volume with cognitive performance exists in healthy as well as in cognitively impaired elderly subjects. Whereas one small study reported an association of BFCS volume with general cognitive ability 'g' in healthy ageing, effects on specific cognitive domains have only been found in subjects with cognitive decline. Here we aim to clarify whether an association of BFCS volume and 'g' is present in a larger sample of elderly subjects without obvious symptoms of dementia and whether similar associations can also be observed in specific cognitive domains. METHODS: 282 pre-surgical patients from the BioCog study (aged 72.7±4.9 years with a range of 65-87 years, 110 women) with a median MMSE score of 29 points (range 24-30) were investigated. BFCS and brain volume as well as brain parenchymal fraction were assessed in T1-weighted MR images using SPM12 and a probabilistic map of the BFCS. Neuropsychological assessment comprised the CANTAB cognitive battery and paper-and-pencil based tests. For data analysis, generalised linear models and quantile regression were applied. RESULTS: Significant associations of BFCS volume with 'g' and several cognitive domains were found, with the strongest association found for 'g'. BFCS volume explained less variance in cognitive performance than brain volume. The association was not confounded by brain parenchymal fraction. Furthermore, the association of BFCS volume and 'g' was similar in high- and low-performers. CONCLUSION: Our results extend previous study findings on BFCS volume associations with cognition in elderly subjects. Despite the observed associations of BFCS volume and cognitive performance, this association seems to reflect a more general association of brain volume and cognition. Accordingly, a specific association of BFCS volume and cognition in non-demented elderly subjects is questionable

Stability of neuropsychological test performance in older adults serving as normative controls for a study on postoperative cognitive dysfunction

OBJECTIVE: Studies of postoperative cognitive dysfunction (POCD) rely on repeat neuropsychological testing. The stability of the applied instruments, which are affected by natural variability in performance and measurement imprecision, is often unclear. We determined the stability of a neuropsychological test battery using a sample of older adults from the general population. Forty-five participants aged 65 to 89 years performed six computerized and non-computerized neuropsychological tests at baseline and again at 7 day and 3 months follow-up sessions. Mean scores on each test were compared across time points using repeated measures analyses of variance (ANOVA) with pairwise comparison. Two-way mixed effects, absolute agreement analyses of variance intra-class correlation coefficients (ICC) determined test-retest reliability. RESULTS: All tests had moderate to excellent test-retest reliability during 7-day (ICC range 0.63 to 0.94; all p < 0.01) and 3-month intervals (ICC range 0.60 to 0.92; all p < 0.01) though confidence intervals of ICC estimates were large throughout. Practice effects apparent at 7 days eased off by 3 months. No substantial differences between computerized and non-computerized tests were observed. We conclude that the present six-test neuropsychological test battery is appropriate for use in POCD research though small sample size of our study needs to be recognized as a limitation. Trial registration ClinicalTrials.gov Identifier NCT02265263 (15th October 2014)

Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study

Objectives To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers