Deficits in geriatric assessment are important in relation to fatigue in older patients with Inflammatory Bowel Disease.

BACKGROUND: No previous study has investigated fatigue in older patients with Inflammatory Bowel Disease (IBD). AIMS: To describe the prevalence of fatigue in older patients and compare it to the prevalence in younger patients with IBD, and to determine factors associated with fatigue. METHODS: A prospective, multicenter cohort study, including older- (≥ 65 years) and younger patients with IBD (18-64 years). A geriatric assessment was performed in older patients to measure deficits in geriatric assessment (DiG). Fatigue was defined by one item from the short Inflammatory Bowel Disease Questionnaire. Active disease was defined as the presence of clinical or biochemical disease activity. RESULTS: Fatigue prevalence in the 405 older patients varied between 45.4% (71/155) in active disease to 23.6% (60/250) in remission. Fatigue prevalence in 155 younger patients was 59.5% (47/79) and 57.4% (89/155), respectively. Female sex, clinical disease activity, use of immunomodulators and presence of DiG were associated with fatigue in older patients with IBD. CONCLUSIONS: Fatigue prevalence is lower in older patients with IBD compared to younger patients with IBD, but increases when active disease is present. Clinicians should be aware that fatigue is a relevant symptom in older patients with IBD, as it is associated with DiG.

Impact of Inflammation on Cognitive Functioning After Electroconvulsive Therapy in Older Patients with Depression with and Without White Matter Hyperintensities.

OBJECTIVE: Should we treat older, patients with depression with white matter hyperintensities (WMH) with electroconvulsive therapy (ECT)? WMH, inflammation, depression and cognitive functioning are suggested to be intertwined. Hence, this study investigates whether the association between inflammation and cognition is different in patients with depression with or without WMH. METHODS: Cognitive functioning was assessed using the Mini-Mental State Examination during and after a course of ECT in 77 older patients with depression. Serum samples (C-reactive protein [CRP], interleukin-6 [IL-6], interleukin-10 [IL-10] and tumour necrosis factor-alpha [TNF-α]) and 3T magnetic resonance imaging were obtained prior to ECT. RESULTS: An interaction effect was found for IL-10, but not for CRP, IL-6 or TNF-α. CONCLUSION: In general, the association between inflammatory markers and cognition in patients with depression treated with ECT is not different in patients with WMH compared to patients without WMH.

The Role of Insulin-Like Growth Factor 1 in Delirium: A Systematic Review and Meta-Analysis.

BACKGROUND: The relationship between delirium and low levels of insulin-like growth factor 1 (IGF-1) is contradictory and uncertain. We hypothesised that low levels of IGF-1 are a predisposing factor for delirium in medical and abdominal surgical cohorts, in contrast to other surgical cohorts. AIMS: Systematic review and meta-analysis investigating the association between peripheral levels of IGF-1 and delirium in medical and surgical patients to explore if there are distinct patterns of associations by using subgroup meta-analysis. METHODS: PubMed, Scopus, CINAHL, Cochrane, and Embase databases were searched. Inclusion criteria were prospective studies in medical and surgical populations and available data. The following were collected: the setting (surgical/medical), the type (orthopaedic surgery, abdominal, cardiovascular, or medical), the number of participants, mean age, the number of delirious patients, scale/criteria for delirium, IGF-1 levels, and MMSE. RESULTS: Thirteen studies were included and analysed. Low levels of IGF-1 are significantly associated with delirium in abdominal surgical samples and medical samples but not in the other surgical samples. Age, cognition, and the setting (medical vs. surgical) do not have any significant effect on the differences in IGF-1 levels between those with and without delirium. DISCUSSION: Delirium in acute medical and abdominal surgery is triggered by low IGF-1 which may reflect chronic conditions like frailty/cachexia/sarcopenia, while in other surgeries perhaps from an inflammatory process. CONCLUSIONS: Low peripheral levels of IGF-1 are a predisposing factor for delirium only in acute medical and abdominal surgery. More studies are needed to confirm and to explore further this finding.

Consistent patterns in the inconsistent associations of Insulin-like growth factor 1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin 6 (IL-6) levels with delirium in surgical populations. A systematic review and meta-analysis.

BACKGROUND: Biomarkers for delirium could increase diagnostic accuracy and may help to identify pathological pathways. Until now study findings concerning cytokine levels have been inconsistent. AIMS: Systematic review and meta-analysis investigating the association between peripheral levels of Insulin-like Growth Factor-1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin-6 (IL-6) and delirium in surgical patients, and to explore if there are distinct/specific patterns that may potentially explain inconsistent results. METHODS: PubMed, Scopus, CINAHL, Cochrane, and EMBASE databases were searched. Inclusion criteria were: prospective studies, surgical populations excluding preoperative delirium, available data. The following were collected: type of operation (orthopaedic, abdominal, etc), the timing of operation (acute, elective, both), demographics, number of participants with delirium, time of preoperative blood withdrawal, and preoperative levels of each biomarker. RESULTS: Low levels of IGF-1 (n = 7 studies) are significantly associated with post-operative delirium in abdominal surgical samples. High levels of C-RP (n = 9) are associated with delirium in acute orthopaedic and elective abdominal operations. IL-6 (n = 14) is a significant predictor of post-operative delirium in a variety of surgical conditions (elective or acute). DISCUSSION: A common pattern exists in the otherwise conflicting reported findings. This similarity may reflect different underling mechanisms and predisposing factors like cachexia and catabolic stages. It seems that delirium in abdominal surgery is triggered by IGF-1 disturbances, while in other surgeries by an inflammatory reaction. CONCLUSIONS: Despite the contradictory results concerning the association of IGF-1, C-RP and IL-6 with postoperative delirium, the present meta-analysis shows that there are certain patterns. IL-6 seems a consistent predictor for delirium in surgical samples.

Inflammation and Cognitive Functioning in Depressed Older Adults Treated With Electroconvulsive Therapy: A Prospective Cohort Study.

Objective: Despite the effectiveness of electroconvulsive therapy (ECT), patients and practitioners are often reluctant to start it due to the risk of transient cognitive side effects, particularly in older patients. Inflammatory processes may be associated with the occurrence of these effects. This study assessed whether inflammatory markers prior to ECT are associated with cognitive functioning in depressed patients treated with ECT.Methods: Between 2011 and 2013, 97 older patients (mean [SD] age = 73.1 [8.1] years) with severe unipolar depression (according to DSM-IV) referred for ECT were included. Mini-Mental State Examination (MMSE) scores were used to determine cognitive functioning prior to, weekly during, and in the first week after a course of ECT. Serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were assessed prior to ECT.Results: In fully adjusted models, there was an association between TNF-α and cognitive functioning (ß = -1.05; 95% CI, -2.04 to -0.06; f2 = 0.06). An association was also found between baseline levels of IL-10 and TNF-α and lower MMSE scores during ECT (IL-10: ß = -2.08; 95% CI, -3.22 to -0.95; TNF-α: ß = -0.65; 95% CI, -1.07 to -0.22). In addition, an association was found between baseline CRP and lower MMSE scores directly after a course of ECT (ß = -0.51; 95% CI, -0.93 to -0.09; f2 = 0.10). Associations with IL-6 did not reach significance.Conclusions: This study suggests that inflammatory processes are associated with lower cognitive functioning prior to ECT and predispose for further cognitive dysfunction during and after a course of ECT.Trial registration: ClinicalTrials.gov identifier: NCT02667353.

The pattern of inflammatory markers during electroconvulsive therapy in older depressed patients.

OBJECTIVES: An association is found between changes in cytokine levels and antidepressant treatment outcome. Also, a proinflammatory profile is associated with a favourable electroconvulsive therapy (ECT) outcome. This paper investigates the pattern of inflammatory markers during a course of ECT in older depressed patients and whether this pattern is associated with ECT outcome. We hypothesised that ECT has an anti-inflammatory effect. METHODS: The pattern of CRP, IL-6, IL-10, and TNF-α during a course of ECT was examined using longitudinal mixed model analyses. Serum samples were collected in 99 older depressed patients (mean age: 72.8 ± 8.3 years, MADRS score 33.8 ± 9.0). RESULTS: After Bonferroni correction, there were no statistically significant alterations in levels of inflammatory markers during and after ECT. Effect sizes (Cohen's d) were -0.29 for CRP, -0.13 for IL-6, -0.06 for IL-10, and -0.07 for TNF-α. Changes in CRP or cytokine levels did not differ between remitters and non-remitters. Median baseline levels of CRP were significantly higher in remitters. CONCLUSIONS: A small to medium effect size towards decreased CRP and IL-6 levels was observed. An anti-inflammatory effect of ECT could not be confirmed. However, the findings may suggest that patients with an inflammatory profile benefit more from ECT than other patients. Further studies are needed to confirm these findings.

Are Apathy and Depressive Symptoms Related to Vascular White Matter Hyperintensities in Severe Late Life Depression?

OBJECTIVE: Apathy symptoms are defined as a lack of interest and motivation. Patients with late-life depression (LLD) also suffer from lack of interest and motivation and previous studies have linked apathy to vascular white matter hyperintensities (WMH) of the brain in depressed and nondepressed patients. The aim of this study was to investigate the relationship between apathy symptoms, depressive symptoms, and WMH in LLD. We hypothesize that late-onset depression (LOD; first episode of depression after 55 years of age) is associated with WMH and apathy symptoms. METHODS: Apathy scores were collected for 87 inpatients diagnosed with LLD. Eighty patients underwent brain magnetic resonance imaging. Associations between depressive and apathy symptoms and WMH were analyzed using linear regression. RESULTS: All 3 subdomains of the 10-item Montgomery-Åsberg Depression Rating Scale correlated significantly with the apathy scale score (all P < .05). In the total sample, apathy nor depressive symptoms were related to specific WMH. In LOD only, periventricular WMH were associated with depression severity (ß = 5.21, P = .04), while WMH in the left infratentorial region were associated with apathy symptoms (ß coefficient = 5.89, P = .03). CONCLUSION: Apathy and depressive symptoms are highly overlapping in the current cohort of older patients with severe LLD, leading to the hypothesis that apathy symptoms are part of depressive symptoms in the symptom profile of older patients with severe LLD. Neither apathy nor depressive symptoms were related to WMH, suggesting that radiological markers of cerebrovascular disease, such as WMH, may not be useful in predicting these symptoms in severe LLD.

Delirium, insulin-like growth factor I, growth hormone in older inpatients.

BACKGROUND: Delirium is a common disorder in elderly medical inpatients with serious adverse outcomes and is characterized by sudden onset, disturbance in attention, awareness, consciousness and cognition, and often with behavioural disturbances. Central to understanding delirium, is understanding mechanisms by which body and brain wellbeing are linked and in particular how brain responses to bodily homeostatic stress is mediated. A number of studies have investigated the relationship between insulin-like growth factor I (IGF-I) and delirium in medically ill hospitalised patients with conflicting results. However, none have investigated growth hormone (GH) which is related to IGF-I via negative feedback. AIM: To investigate the relationship between serum levels of IGF-I and GH, and the occurrence of delirium. METHODS: Prospective, longitudinal, observational study. Consecutive elderly inpatients (aged 70+), were assessed twice weekly with Montreal cognitive assessment (MoCA), Confusion assessment method (CAM), Acute Physiology and Chronic Health Evaluation II. Delirium was defined using CAM. Previous history of dementia was evaluated with the Informant Questionnaire on Cognitive Decline in the Elderly. IGF-I and GH levels were estimated with the ELISA method. Generalized estimating equations (GEE) model was applied for the first five assessments to analyze those longitudinal data. RESULTS: The sample consisted of 198 participants (mean age 80.63 ± 6.81; range 70-97). Of these 92 (46.5%) were females. Eighty six (43.4%) were identified with a history of dementia. Incident or prevalent delirium during hospitalisation was identified with CAM in 40 participants (20.2%). Evaluation of missing values with Little's MCAR test indicated that they were missing completely at random (MCAR χ 2 = 12.24, u: 9, P = 0.20). Using GEE for the analysis we found that low MoCA scores, low levels of IGF-I and high levels of GH were significantly associated with any delirium (prevalence, incident, or fluctuating , during the study period (Wald χ 2 = 12.231; u: 1, P < 0.001, Wald χ 2 = 7.196, u: 1, P = 0.007, Wald χ 2 = 6.210; : u: 1, P = 0.013 respectively). CONCLUSION: The results show that low levels of IGF-I, high levels of GH and low scores in cognition are independently associated with the occurrence of any delirium during the hospitalisation of medically ill older people. The results of the study supports the hypothesis that deficits in the immunoreactivity of the brain (low cerebral reserve) may be associated with delirium.

Preoperative Cerebrospinal Fluid Cortisol and the Risk of Postoperative Delirium: A Prospective Study of Older Hip Fracture Patients.

BACKGROUND: Ageing, depression, and neurodegenerative disease are common risk factors for delirium in the elderly. These risk factors are associated with dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in higher levels of cortisol under normal and stressed conditions and a slower return to baseline. OBJECTIVES: We investigated whether elevated preoperative cerebrospinal fluid (CSF) cortisol levels are associated with the onset of postoperative delirium. METHODS: In a prospective cohort study CSF samples were collected after cannulation for the introduction of spinal anesthesia of 75 patients aged 75 years and older admitted for surgical repair of acute hip fracture. Delirium was assessed with the confusion assessment method (CAM) and the Delirium Rating Scale-Revised-98 (DRS-R98). Because the CAM and DRS-R98 were available for time of admission and 5 postoperative days, we used generalized estimating equations and linear mixed modeling to examine the association between preoperative CSF cortisol levels and the onset of postoperative delirium. RESULTS: Mean age was 83.5 (SD 5.06) years, and prefracture cognitive decline was present in one-third of the patients (24 [33%]). Postoperative delirium developed in 27 (36%) patients. We found no association between preoperative CSF cortisol levels and onset or severity of postoperative delirium. CONCLUSIONS: These findings do not support the hypothesis that higher preoperative CSF cortisol levels are associated with the onset of postoperative delirium in elderly hip fracture patients.

S100 calcium-binding protein B in older patients with depression treated with electroconvulsive therapy.

BACKGROUND: Increasing evidence suggests that glial mediated disruption of neuroplasticity contributes to depression. S100 calcium-binding protein B (S100B) promotes neuronal protection in nanomolar concentrations. Studies on its possible role as a treatment outcome marker in affective disorders are limited. Recent evidence suggests a putative role for S100B as a state marker of illness activity as it is found elevated in episodes of major depression. AIM: To investigate whether higher S100B is associated with favourable treatment outcome following electroconvulsive therapy (ECT) and to further explore whether S100B reflects a state marker of depression activity. METHODS: Serum S100B samples, at baseline and post-ECT and clinical assessments including Montgomery Åsberg Rating scales were collected in 91 older depressed patients (mean age: 73.0 years), referred for ECT. Change in pre- and post-ECT S100B was compared between remitters and nonremitters. Logistic and Cox regression analyses were used to determine whether S100B was associated with remission of depression. RESULTS: Patients with S100B levels in the intermediate tertile, that is, between 33 ng/L and 53 ng/L, had higher odds on remission, odds ratio: 5.5 (95%Confidence Interval (CI): 1.55-19.20, p = <0.01), and were more likely to remit from depression over time, hazard ratio: 1.96 (95%CI: 1.04-3.72, p = 0.04), compared with patients in the lowest tertile. There was no significant decrease in levels of S100B after ECT in both remitters and nonremitters. CONCLUSION: Our findings demonstrate that patients with higher S100B levels at baseline were more likely to remit from depression suggesting an association between higher S100B and responsiveness to ECT. Next, S100B levels do not decrease after remission, suggesting S100B is not a state marker of depression. S100B is not capable of predicting treatment outcome by itself, further research may combine outcome markers.

Inflammation and remission in older patients with depression treated with electroconvulsive therapy; findings from the MODECT study✰.

BACKGROUND: Compelling evidence links elevated levels of C-reactive protein (CRP) and other inflammatory markers to poor treatment outcome of antidepressant medication. Little is known about the contribution of low-grade inflammation to treatment response to electroconvulsive therapy (ECT) in severely depressed patients. METHOD: Associations between serum levels of CRP, interleukin-6, interleukin-10, and tumour necrosis factor-α as well as remission of depression, time to remission, and speed of decline of depressive symptoms were examined in 95 older (mean age: 73.1 years) depressed patients treated with ECT. RESULTS: Moderately elevated levels of CRP at baseline (3 to 10 mg/L), but no other inflammatory markers, were associated with higher remission rates. In patients with moderately elevated CRP levels, the odds ratio for remission was 3.62 (95% confidence interval [CI], 1.09-11.97; p = 0.04). Time to remission was shorter in those with moderately elevated CRP levels (p = 0.05). Speed of decline was higher in patients with moderately elevated CRP levels as compared with those with low CRP levels (decline of 3.2 Montgomery Åsberg Depression Rating Scale points per administration vs. 2.3 points per administration, p = 0.03). LIMITATIONS: Because of the observational design, residual confounding through other lifestyle or demographic factors cannot be ruled out. CONCLUSIONS: Although earlier studies showed that low-grade inflammation contributes to poor treatment response in those treated with antidepressants, our study provides clues that low-grade inflammation does not have such a detrimental effect on the treatment response to ECT. This is underscored by our finding that moderately elevated CRP levels were associated with increased remission rates in depressed patients treated with ECT. Replication studies are warranted.

The trajectory of C-reactive protein serum levels in older hip fracture patients with postoperative delirium.

OBJECTIVES: Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. METHODS: This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C-reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. RESULTS: Forty-one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1-2 days) and more prolonged delirium (3 days or more). CONCLUSIONS: Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory-vascular) pathological pathway of postoperative delirium.

Exploring resting state connectivity in patients with psychotic depression.

BACKGROUND: Severe depression is associated with high morbidity and mortality. Neural network dysfunction may contribute to disease mechanisms underlying different clinical subtypes. Here, we apply resting-state functional magnetic resonance imaging based measures of brain connectivity to investigate network dysfunction in severely depressed in-patients with and without psychotic symptoms. METHODS: A cohort study was performed at two sites. Older patients with major depressive disorder with or without psychotic symptoms were included (n = 23 at site one, n = 26 at site two). Resting state 3-Tesla functional MRI scans, with eyes closed, were obtained and Montgomery-Åsberg Depression Rating Scales were completed. We denoised data and calculated resting state networks in the two groups separately. We selected five networks of interest (1. bilateral frontoparietal, 2.left lateralized frontoparietal, 3.right lateralized frontoparietal, 4.default mode network (DMN) and 5.bilateral basal ganglia and insula network) and performed regression analyses with severity of depression, as well as presence or absence of psychotic symptoms. RESULTS: The functional connectivity (FC) patterns did not correlate with severity of depression. Depressed patients with psychotic symptoms (n = 14, 61%) compared with patients without psychotic symptoms (n = 9, 39%) from site one showed significantly decreased FC in the right part of the bilateral frontoparietal network (p = 0.002). This result was not replicated when comparing patients with (n = 9, 35%) and without (n = 17, 65%) psychotic symptoms from site two. CONCLUSION: Psychotic depression may be associated with decreased FC of the frontoparietal network, which is involved in cognitive control processes, such as attention and emotion regulation. These findings suggest that FC in the frontoparietal network may be related to the subtype of depression, i.e. presence of psychotic symptoms, rather than severity of depression. Since the findings could not be replicated in the 2nd sample, replication is needed before drawing definite conclusions.

The Pitfall of Behavioral Variant Frontotemporal Dementia Mimics Despite Multidisciplinary Application of the FTDC Criteria.

BACKGROUND: The behavioral variant of frontotemporal dementia (bvFTD) has a broad differential diagnosis including other neurological and psychiatric disorders. Psychiatric misdiagnoses occur in up to 50% of bvFTD patients. Numbers on misdiagnosis of bvFTD in psychiatric disorders are lacking. OBJECTIVE: The aim of our study was to investigate the frequency and characteristics of bvFTD misdiagnoses in psychiatric disorders and other neurologic disorders. METHODS: Thirty-five patients with a (possible or probable) bvFTD diagnosis made by specialized memory clinic neurologists were included. Change in diagnosis after consulting a psychiatrist at baseline was recorded as well as change in diagnosis after two years of multidisciplinary neuropsychiatric follow-up. Differences in cognitive and behavioral profiles were investigated per diagnostic group after follow-up (bvFTD, psychiatry, other neurologic disorders). Clinical profiles are described in detail. RESULTS: In 17 patients (48.5%), the bvFTD baseline diagnosis changed: Two at baseline after psychiatric consultation, and 15 after two years of multidisciplinary follow-up. Eleven (64.5%) of these 17 patients (31.5% of total) were reclassified with a psychiatric diagnosis. We found no differences for cognitive baseline profiles between patients with bvFTD versus psychiatric diagnoses. CONCLUSION: In almost half of cases, the initial bvFTD diagnosis was changed after follow-up, most often into a psychiatric disorder. A multidisciplinary neuropsychiatric approach in the diagnostic process of bvFTD results in the identification of treatable disorders. Our findings illustrate a limited specificity of the [18F]FDG-PET-scan and the bvFTD criteria in a neuropsychiatric cohort, especially combined with certain clinical symptoms, like disinhibition, apathy, or loss of empathy.

Early- and Late-Onset Depression in Late Life: A Prospective Study on Clinical and Structural Brain Characteristics and Response to Electroconvulsive Therapy.

OBJECTIVE: The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset <55 and ≥55 years). METHODS: Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT-treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study. Clinical profile and somatic health were assessed. Magnetic resonance imaging (MRI) scans were performed before the first ECT and visually rated. RESULTS: Response rate was 78.2% and similar between the two sites but significantly higher in LOD compared with EOD (86.9 versus 67.3%). Clinical, somatic, and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. CONCLUSION: The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients.

Mortality and Its Determinants in Late-Life Schizophrenia: A 5-Year Prospective Study in a Dutch Catchment Area.

OBJECTIVE: It is uncertain if the raised mortality in schizophrenia persists in later life. Register-based studies suggest that excess mortality continues, although at a lower level than in younger age groups. However, prospective follow-up studies of older schizophrenia samples are lacking. METHODS: A cohort of 157 older patients (mean age at study entry: 68 years) diagnosed with schizophrenia or schizoaffective disorder in a psychiatric catchment area in Amsterdam, the Netherlands was studied. Standardized mortality rate (SMR) was estimated at a 5-year follow-up, in referral to the same age group in the general catchment area population. The impact on survival time of a range of independent demographic and clinical predictors was evaluated. RESULTS: The cohort had an all-cause SMR of 1.89 (95% CI: 1.28-2.70). SMR was higher in men (2.60; 95% CI: 1.42-4.37) than in women (1.78; 95% CI: 1.02-2.90). All deaths were from natural causes. Reduced survival was associated with higher age (HR: 1.10; 95% CI: 1.05-1.16), male gender (HR: 3.94; 95% CI: 1.87-8.31), and having had one or more compulsory admissions in the past (HR: 2.61; 95% CI: 1.46-4.68). In contrast, no mortality associations were found with diagnosis (schizophrenia versus schizoaffective disorder), age at onset of the disorder, or current prescription of antipsychotics. CONCLUSION: The excess mortality in schizophrenia continues into late life, affecting men more often than women. Given the poor insight into the underlying mechanisms of this disquieting finding, there is a need to identify modifiable clinical and social risk factors.

The mediating role of cardiovascular risk factors in the relationship between symptoms of apathy and incident cardiovascular disease in community-dwelling older individuals.

BACKGROUND: In old age, both apathy and depression have been associated with an increased cardiovascular disease (CVD) risk. This study evaluated the mediating role of cardiovascular risk factors in the relationship of apathy and mood symptoms with incident CVD. METHODS: Prospective cohort study of 1,790 community-dwelling older individuals (70-78 years) without a history of CVD or stroke. At baseline, apathy and mood symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15), of which three items represent apathy symptoms. The mediational risk factors included were diabetes mellitus (DM), body mass index (BMI), current smoking, physical inactivity, systolic blood pressure, and total cholesterol. Incident CVD was evaluated after two years of follow-up. Data were analyzed using structural equation modeling (SEM). RESULTS: Incident CVD occurred in 59 (3.3%) participants. Apathy symptoms had a significant estimated total effect on incident CVD, with increases of 2.2% for each unit increase in apathy score. Of this total effect, 22.7% was due to the mediational effects of physical inactivity (13.6%), current smoking (4.5%), and DM (4.5%). The remaining 77.3% was due to direct effects reflecting other mediational dynamics. No significant (in)direct effects of mood symptoms on incident CVD were found. CONCLUSIONS: Physical inactivity, smoking, and DM account for nearly one-fourth of the variation reflecting the link between apathy symptoms and incident CVD. This illustrates the relevance of unfavorable health behaviors and assessment of DM in older individuals with apathy. The majority of the effect of apathy symptoms on incident CVD is caused by other, yet unknown, factors.

Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium: A proteomics and validation study.

BACKGROUND: A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery. METHODS: Patients (≥ 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays. RESULTS: In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium. CONCLUSION: Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings. GENERAL SIGNIFICANCE: This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling.

Contribution of white matter hyperintensities, medial temporal lobe atrophy and cortical atrophy on outcome, seven to twelve years after ECT in severely depressed geriatric patients.

BACKGROUND: Depression and cognitive decline are highly prevalent and often coexisting, however, the association between depression and dementia remains unclear. White matter hyperintensities (WMH), medial temporal lobe atrophy (MTA) and global cortical atrophy (GCA) are associated with depression, mild cognitive impairment and dementia; these structural abnormalities may therefore represent a common underlying mechanism of these diseases. We conducted a naturalistic prospective follow-up study in patients with severe geriatric depression who were formerly treated with ECT. The aim of the study was to investigate the effects of structural abnormalities in the brain on cognitive decline, dementia and survival. METHOD: Survival data of 76 patients was obtained. 39 (51.3%) of them also participated in the follow-up study. Cognitive decline was identified 7-12 years after ECT (median 8.0), using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A diagnosis of dementia was obtained from the family doctor of the patients. RESULTS: Forty-two out of the 76 (55.3%) of the patients died during follow-up. Twenty-four out of the remained 39 (65.1%) patients who participated in the follow-up study reported cognitive decline and 7 among the 39 patients (17.9%) were diagnosed with dementia. Depression with psychotic symptoms was significantly associated with absence of cognitive decline at follow-up (p=0.007). WMH was significantly associated with mortality (plog rank=0.048). Finally, we observed a trend in significance between the association of GCA and cognitive decline at follow-up (p=0.078), CONCLUSIONS: Depression with psychotic symptoms is a depression subtype that might not be associated with cognitive decline at follow-up. Moderate or severe WMH before ECT in our cohort of depressed patients was associated with higher mortality and GCA was possibly associated with cognitive decline at follow-up.

Low-grade inflammation differentiates between symptoms of apathy and depression in community-dwelling older individuals.

BACKGROUND: Systemic low-grade inflammation has repeatedly been associated with depression in old age, but the relationship with apathy is less clear. The present study assessed whether C-reactive protein (CRP) is differentially associated with symptoms of apathy and depression. METHODS: A population-based cohort study was carried-out. At baseline and after two and four years of follow-up, CRP levels were assessed and symptoms of apathy and depression were measured using the 15-item Geriatric Depression Scale. Logistic regression analysis was used to investigate the cross-sectional and longitudinal associations of CRP with symptoms of apathy and depression. RESULTS: Two thousand forty-seven community-dwelling participants (70-78 years) without a history of cardiovascular disease or stroke were studied. A cross-sectional association was found between CRP and apathy symptoms at three time points (odds ratio (OR) per natural log unit increase in CRP: baseline visit = 1.40, 95% CI = 1.12-1.75; two-year follow-up visit = 1.62, 95% CI = 1.17-2.25; four-year follow-up visit = 1.51, 95% CI = 1.03-2.21). This did not change after adjustment for demographics and depressive symptoms, and was slightly attenuated after adjustment for cardiovascular risk factors. No cross-sectional association was found with depressive symptoms. Baseline CRP did not predict incident apathy or depressive symptoms during four years of follow-up. CONCLUSIONS: Increased CRP levels are associated with apathy symptoms but not with depressive symptoms. This suggests a differential effect of inflammation on apathy and depression. In older persons, symptoms of apathy may be a behavioral manifestation of concurrent low-grade inflammation.