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.

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.

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.

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.

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.

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.

Apolipoproteins E and J interfere with amyloid-beta uptake by primary human astrocytes and microglia in vitro.

Defective clearance of the amyloid-ß peptide (Aß) from the brain is considered a strong promoter in Alzheimer's disease (AD) pathogenesis. Astrocytes and microglia are important mediators of Aß clearance and Aß aggregation state and the presence of amyloid associated proteins (AAPs), such as Apolipoproteins E and J (ApoE and ApoJ), may influence Aß clearance by these cells. Here we set out to investigate whether astrocytes and microglia differ in uptake efficiency of Aß oligomers (Aßoligo ) and Aß fibrils (Aßfib ), and whether the Aß aggregation state and/or presence of AAPs affect Aß uptake in these cells in vitro. Adult human primary microglia and astrocytes, isolated from short delay post-mortem brain tissue, were exposed to either Aßoligo or Aßfib alone or combined with a panel of certain AAPs whereafter Aß-positive cells were quantified using flow cytometry. Upon exposure to Aß combined with ApoE, ApoJ, α1-antichymotrypsin (ACT) and a combination of serum amyloid P and complement C1q (SAP-C1q), a clear reduction in astrocytic but not microglial Aßoligo uptake, was observed. In contrast, Aßfib uptake was strongly reduced in the presence of AAPs in microglia, but not in astrocytes. These data provide the first evidence of distinct roles of microglia and astrocytes in Aß clearance. More importantly we show that Aß clearance by glial cells is negatively affected by AAPs like ApoE and ApoJ. Thus, targeting the association of Aß with AAPs, such as ApoE and ApoJ, could serve as a therapeutic strategy to increase Aß clearance by glial cells.

White matter hyperintensities and cognitive impairment during electroconvulsive therapy in severely depressed elderly patients.

OBJECTIVE: Transient cognitive impairment during electroconvulsive therapy (ECT) can be a reason to discontinue ECT in depressed elderly patients. We hypothesized that both white matter hyperintensities and medial temporal lobe atrophy contribute to transient cognitive impairment during ECT. METHODS: In 81 elderly patients with depression, magnetic resonance images (MRI) were recorded before ECT. We rated white matter hyperintensities (WMH) with the Age-Related White Matter Changes scale (ARWMC). Cognitive impairment during ECT was measured weekly with the Mini Mental State Examination (MMSE), 2 days after each session. RESULTS: The mean MMSE score at baseline for all patients was 25.5 points, the lowest MMSE score during ECT was 23.3 points, and the mean MMSE score after ECT was 26.3 points. Stratification for the ECT method showed no significant difference in the lowest MMSE scores of patients with or without WMH, receiving unilateral ECT (22.5 points versus 23.9 points). There was a difference in the lowest MMSE scores in patients who switched from unilateral ECT to bilateral ECT (18.7 points in patients with WMH versus 22.0 points in patients without WMH). CONCLUSION: Depressed elderly patients with WMH who receive bilateral ECT are at increased risk of transient cognitive impairment. Our findings show, however, that cognitive impairment improves when ECT is continued. This implies that ECT does not have to be discontinued when patients experience transient cognitive impairment during ECT.

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.

Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients.

BACKGROUND: Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. METHODS: Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann-Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. RESULTS: Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. CONCLUSIONS: Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process. TRIAL REGISTRATION: The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient. REGISTRATION NUMBER: NCT00497978. Local ethical protocol number: NL16222.094.07.

The care needs of elderly patients with schizophrenia spectrum disorders.

OBJECTIVE: Elderly patients constitute the fastest growing segment of the schizophrenia population. Still, their needs for care are poorly understood. This study aimed to gain insight into the care needs of older patients with schizophrenia spectrum disorders. SETTING AND PARTICIPANTS: Patients, aged 60 years and older, in contact with mental health services within a Dutch psychiatric catchment area, diagnosed with schizophrenia spectrum disorders. MEASUREMENTS: Needs and the extent to which these were met were assessed from the perspective of both patients and staff members. Agreement between patients and staff on the presence of needs was evaluated. In addition, the association between patient characteristics and the number of unmet needs was examined. RESULTS: On average, patients (N = 114, mean age: 69 years) reported 7.6 needs, of which 6.1 were met and 1.5 were unmet. Staff members reported slightly more needs, both met and unmet. Patients and staff showed consensus on the presence of most needs, but discrepancies existed in individual need areas. Psychological and social needs were unmet more often than environmental and physical needs. The number of unmet needs correlated with several patient variables, with the strongest association found for self-reported quality of life. CONCLUSION: In elderly schizophrenia patients, similar to what has been reported in younger patients, psychological and social needs appear to be under serviced. Having more unmet needs was associated with a lower perceived quality of life.

Cognitive impairment in late life schizophrenia and bipolar I disorder.

OBJECTIVE: Evidence in younger populations suggests quantitative but not categorical differences in cognitive impairments between schizophrenia and bipolar disorder. It is uncertain whether a similar distinction applies to patients in later life. METHODS: We compared the cognitive abilities of older, community-living schizophrenia patients, controlling for their state of symptomatic remission, with those of older euthymic patients with bipolar I disorder. The study included 67 patients with schizophrenia (20 in symptomatic remission, 47 not in symptomatic remission; mean age 68 years) and 74 euthymic bipolar I patients (mean age 70 years), who were compared using analysis of covariance on clinical and neuropsychological variables (e.g., attention/working memory, verbal memory, executive function and verbal fluency) and contrasted with 69 healthy controls. RESULTS: Remitted (SR) and non-remitted (SN) schizophrenia patients and bipolar I (BP) patients were impaired relative to healthy controls, with mostly large effect sizes for verbal memory (Cohen's d: SR 1.34, SN 1.48, BP 1.09), executive function (Cohen's d: SR 0.87, SN 1.29, BP 0.71) and verbal fluency (Cohen's d: SR 1.09, SN 1.25, BP 0.88), but smaller effect sizes for the domain of attention/working memory (Cohen's d: SR 0.26, SN 0.18, BP 0.52). Differences in cognitive performance between the remitted schizophrenia patients and the bipolar I patients were not significant. CONCLUSIONS: In both older patients with schizophrenia and with bipolar disorder, serious and pervasive cognitive deficits can be demonstrated. Trait-related cognitive deficits in schizophrenia and bipolar disorder may share major phenotypic similarity in later life.

Affective functioning after delirium in elderly hip fracture patients.

BACKGROUND: Delirium in elderly patients is associated with various long-term sequelae that include cognitive impairment and affective disturbances, although the latter is understudied. METHODS: For a prospective cohort study of elderly patients undergoing hip fracture surgery, baseline characteristics and affective and cognitive functioning were assessed preoperatively. During hospital admission, presence of delirium was assessed daily. Three months after hospital discharge, affective and global cognitive functioning was evaluated again in patients free from delirium at the time of this follow-up. This study compared baseline characteristics and affective functioning between patients with and without in-hospital delirium. We investigated whether in-hospital delirium is associated with increased anxiety and depressive levels, and post-traumatic stress disorder (PTSD) symptoms three months after discharge. RESULTS: Among 53 eligible patients, 23 (43.4%) patients experienced in-hospital delirium after hip fracture repair. Patients who had experienced in-hospital delirium showed more depressive symptoms at follow-up after three months compared to the 30 patients without in-hospital delirium. This association persisted in a multivariate model controlling for age, baseline cognition, baseline depressive symptoms, and living situation. The level of anxiety and symptoms of PTSD at follow-up did not differ between both groups. CONCLUSION: This study suggests that in-hospital delirium is associated with an increased burden of depressive symptoms three months after discharge in elderly patients who were admitted to the hospital for surgical repair of hip fracture. Symptoms of depression in patients with previous in-hospital delirium cannot be fully explained by persistent (sub)syndromal delirium or baseline cognitive impairment.

The neuropsychological sequelae of delirium in elderly patients with hip fracture three months after hospital discharge.

BACKGROUND: Delirium is a risk factor for long-term cognitive impairment and dementia. Yet, the nature of these cognitive deficits is unknown as is the extent to which the persistence of delirium symptoms and presence of depression at follow-up may account for the association between delirium and cognitive impairment at follow-up. We hypothesized that inattention, as an important sign of persistent delirium and/or depression, is an important feature of the cognitive profile three months after hospital discharge of patients who experienced in-hospital delirium. METHODS: This was a prospective cohort study. Fifty-three patients aged 75 years and older were admitted for surgical repair of acute hip fracture. Before the surgery, baseline characteristics, depressive symptomatology, and global cognitive performance were documented. The presence of delirium was assessed daily during hospital admission and three months after hospital discharge when patients underwent neuropsychological assessment. RESULTS: Of 27 patients with in-hospital delirium, 5 were still delirious after three months. Patients with in-hospital delirium (but free of delirium at follow-up) showed poorer performance than patients without in-hospital delirium on tests of global cognition and episodic memory, even after adjustment for age, gender, and baseline cognitive impairment. In contrast, no differences were found on tests of attention. Patients with in-hospital delirium showed an increase of depressive symptoms after three months. However, delirium remained associated with poor performance on a range of neuropsychological tests among patients with few or no signs of depression at follow-up. CONCLUSION: Elderly hip fracture patients with in-hospital delirium experience impairments in global cognition and episodic memory three months after hospital discharge. Our results suggest that inattention, as a cardinal sign of persistent delirium or depressive symptomatology at follow-up, cannot fully account for the poor cognitive outcome associated with delirium.

Schizophrenia spectrum disorders in later life: prevalence and distribution of age at onset and sex in a dutch catchment area.

OBJECTIVES: The prevalence of schizophrenia in later life is affected by both outflow of early onset patients, due to recovery and excess mortality, and inflow of patients with a later age at onset, making it likely that characteristics of older patients differ markedly from younger patients. We assessed the prevalence of schizophrenia and spectrum disorders and their distribution according to age at onset and sex in an elderly population. DESIGN: Case register study. SETTING AND PARTICIPANTS: All patients age 60 years and older, in contact with the Mental Health Organization in a psychiatric catchment area in Amsterdam (the Netherlands), diagnosed with schizophrenia, schizoaffective disorder, or delusional disorder. MEASUREMENTS: One-year prevalence estimates, including rates according to age group, age at onset, and sex. In addition, we determined the effect of using different criteria for age at onset. RESULTS: The one-year prevalence of all disorders was 0.71%, subdivided in 0.55% for schizophrenia, 0.14% for schizoaffective disorder, and 0.03% for delusional disorder. The one-year prevalence of early-onset schizophrenia was 0.35%, of late-onset schizophrenia 0.14%, and of very-late-onset schizophrenia-like psychosis 0.05%. Variation of onset criterion affected the proportion of early-onset versus late-onset schizophrenia patients stronger in women than in men. Women outnumbered men markedly in the prevalence estimates for most diagnostic subgroups, including early-onset schizophrenia. CONCLUSIONS: We found the prevalence of schizophrenia among older persons to be well within the range reported for younger populations. The considerable proportion with a later age at onset and the strong female preponderance are distinguishing characteristics of older patients with clinical implications.

Routine use of the confusion assessment method for the intensive care unit: a multicenter study.

RATIONALE: Delirium is often unrecognized in ICU patients and associated with poor outcome. Screening for ICU delirium is recommended by several medical organizations to improve early diagnosis and treatment. The Confusion Assessment Method for the ICU (CAM-ICU) has high sensitivity and specificity for delirium when administered by research nurses. However, test characteristics of the CAM-ICU as performed in routine practice are unclear. OBJECTIVES: To investigate the diagnostic value of the CAM-ICU in daily practice. METHODS: Teams of three delirium experts including psychiatrists, geriatricians, and neurologists visited 10 ICUs twice. Based on cognitive examination, inspection of medical files, and Diagnostic and Statistic Manual of Mental Disorders, 4th edition, Text Revision criteria for delirium, the expert teams classified patients as awake and not delirious, delirious, or comatose. This served as a gold standard to which the CAM-ICU as performed by the bedside ICU-nurses was compared. Assessors were unaware of each other's conclusions. MEASUREMENTS AND MAIN RESULTS: Fifteen delirium experts assessed 282 patients of whom 101 (36%) were comatose and excluded. In the remaining 181 (64%) patients, the CAM-ICU had a sensitivity of 47% (95% confidence interval [CI], 35%-58%); specificity of 98% (95% CI, 93%-100%); positive predictive value of 95% (95% CI, 80%-99%); and negative predictive value of 72% (95% CI, 64%-79%). The positive likelihood ratio was 24.7 (95% CI, 6.1-100) and the negative likelihood ratio was 0.5 (95% CI, 0.4-0.8). CONCLUSIONS: Specificity of the CAM-ICU as performed in routine practice seems to be high but sensitivity is low. This hampers early detection of delirium by the CAM-ICU.

Innate immunity and the etiology of late-onset Alzheimer's disease.

BACKGROUND: Neuropathological studies supported by experimental animal studies show that the constituents of the innate immunity are intimately involved in the early steps of the pathological cascade of Alzheimer's disease (AD). OBJECTIVES: To show the evidence that constituents of the innate immunity contribute to the etiology of late-onset AD. METHODS: Evaluation of the relationship between the constituents of the innate immunity and genetic risk factors for late-onset AD. RESULTS: Complement activation and activated microglia are early neuropathogical events in AD brains. Genome-wide association studies have demonstrated gene loci that are linked to the complement system. The production capacity for inflammatory cytokines is under genetic control and the offspring with a parental history of late-onset AD have a higher production capacity for inflammatory cytokines. CONCLUSION: Epidemiological and genetic data suggest that the innate immunity is involved in the etiology of late-onset AD.