Diagnostic Impact of CSF Biomarkers in a Local Hospital Memory Clinic Revisited.

BACKGROUND/AIMS: Research guidelines on predicting and diagnosing Alzheimer's disease (AD) acknowledge cerebrospinal fluid (CSF) levels as pivotal biomarkers. We studied the usefulness of CSF biomarkers in the diagnostic workup of patients in a geriatric outpatient memory clinic of a community-based hospital, attempted to determine a cutoff age for the use of CSF biomarkers in this group of patients, and compared the total τ/Aß ratio as an alternative CSF diagnostic rule with the usual rules for interpreting CSF levels. METHODS: This was a prospective study of consecutively referred patients. Inclusion criteria were described on the basis of previous study results in the same setting. The CSF tool was applied either to differentiate between AD and no AD or to increase certainty having made the diagnosis of AD. Clinicians were asked to judge whether the CSF results were helpful to them or not. RESULTS: The reasons to use the CSF tool in the diagnostic workup were in 78/106 patients to decide between the diagnosis "AD" and "no AD" and in 28/106 patients to increase the certainty regarding the diagnosis. In 75% of cases the CSF levels were considered diagnostically helpful to the clinicians. Results in the present setting suggest 65 years as the cutoff age to use CSF as a diagnostic tool. The sensitivity and specificity of the total τ/Aß ratio using the clinical diagnosis as the gold standard were at least as good as the usual categorization rule. CONCLUSIONS: Our study results corroborate earlier findings that the CSF tool is of added value to the diagnostic workup in daily clinical practice outside tertiary referral centers. CSF levels can best be used in patients under 66 years of age. Given the limited use of this tool in settings outside research facilities, we recommend that the usefulness of CSF biomarkers is studied in a multicenter study. When in the future CSF levels can be reliably measured in plasma, this may become even more relevant.

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.

Course of Cognitive Functioning in Institutionalized Persons With Moderate to Severe Dementia: Evidence From the Severe Impairment Battery Short Version.

OBJECTIVES: To adequately monitor the course of cognitive functioning in persons with moderate to severe dementia, relevant cognitive tests for the advanced dementia stages are needed. We examined the ability of a test developed for the advanced dementia stages, the Severe Impairment Battery Short version (SIB-S), to measure cognitive change over time. Second, we examined type of memory impairment measured with the SIB-S in different dementia stages. METHODS: Participants were institutionalized persons with moderate to severe dementia (N = 217). The SIB-S was administered at 6-month intervals during a 2-year period. Dementia severity at baseline was classified according to Global Deterioration Scale criteria. We used mixed models to evaluate the course of SIB-S total and domain scores, and whether dementia stage at baseline affected these courses. RESULTS: SIB-S total scores declined significantly over time, and the course of decline differed significantly between dementia stages at baseline. Persons with moderately severe dementia declined faster in mean SIB-S total scores than persons with moderate or severe dementia. Between persons with moderate and moderately severe dementia, there was only a difference in the rate of decline of semantic items, but not episodic and non-semantic items. CONCLUSIONS: Although modest floor and slight ceiling effects were noted in severe and milder cases, respectively, the SIB-S proved to be one of few available adequate measures of cognitive change in institutionalized persons with moderate to severe dementia. (JINS, 2019, 25, 204-214).

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.

Clinician and caregiver agreement on neuropsychiatric symptom severity: a study using the Neuropsychiatric Inventory - Clinician rating scale (NPI-C).

BACKGROUND: Neuropsychiatric symptoms (NPS) are highly prevalent in dementia. The recently developed Neuropsychiatric Inventory - Clinician rating scale (NPI-C) includes clinical judgment and new symptom domains. Our objective was to evaluate NPI-C reliability and to compare caregiver and clinician ratings across the range of mild to severe cognitive impairment. METHODS: This is a cross-sectional observational study. Participants were geriatric memory clinic patients and nursing-home residents (n = 30) with an established diagnosis of dementia or Mild Cognitive Impairment (MCI). A psychiatrist (MK) interviewed caregiver-patient dyads using the NPI-C. Neuropsychological tests and Mini-Mental State Examination (MMSE) were used to assess cognitive impairment. Two NPI-C caregiver interviews were videotaped and rated by psychologists and geriatricians. Intra-class correlations (ICCs) were used to examine inter-rater agreement. Correlation coefficients were calculated to evaluate caregiver and psychiatrist NPI-C ratings. Disagreement between caregiver and clinician was expressed in delta scores and examined across the range of mild to severe cognitive impairment, using Levene's homogeneity of variances tests. RESULTS: Inter-rater agreement on ratings of two caregiver videos was high (ICC = 0.99-1.0). Clinician-caregiver concordance on NPI-C total severity ratings was high (r = 0.77). Variability in clinician-caregiver concordance was associated with cognitive impairment: MMSE (P = 0.02), CAMCOG-R (Cambridge Cognitive Examination-revised) total scores (P = 0.02), CAMCOG-R Memory scores (P = 0.04) and Language scores (P = 0.01). CONCLUSIONS: The NPI-C is a reliable measure of NPS in patients with MCI or dementia. Clinician-caregiver agreement on NPS severity may vary with cognitive impairment, underlining the importance of clinician-based measures of NPS.

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.

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.

Detecting delirium in nursing home residents using the Informant Assessment of Geriatric Delirium (I-AGeD): a validation pilot study.

PURPOSE: Early delirium detection in nursing home residents is vital to prevent adverse outcomes. Despite the potential of structured delirium screening tools to enhance delirium detection, they are rarely used in nursing homes. To promote delirium screening tools in nursing homes, they should be easy to integrate into the daily routine of care workers. The I-AGeD, was developed as a simple and easily understandable tool to detect delirium in older adults. The aims of this study were to record the prevalence of delirium, to investigate the feasibility of the I-AGeD, and to compare these results with the DSM-5 as the reference standard. METHODS: This is a cross-sectional prospective single-center pilot study. Seven registered nurses assessed the participants with the I-AGeD. The research assistant conducted delirium assessments based on the DSM-5 criteria, to identify delirium symptoms for the same participants. The feasibility test was verified using a five-point Likert scale ranging from very easy to very difficult. RESULTS: 85 nursing home residents participated in the study. A delirium prevalence of 5.9% was found. The sensitivity was 60% and specificity 94% at a cut point of ≥ 4 to indicate delirium. The feasibility test showed that the 10 items of the I-AGeD were easy or very easy to answer. CONCLUSION: The I-AGeD showed an acceptable performance to assess delirium in nursing home residents. Additionally, it was found feasible and due to its brevity the I-AGeD could easily be integrated into the routine of daily care in nursing homes.

Episodic recognition memory based on incidental learning of visual associations is largely preserved compared to recall in amnestic mild cognitive impairment and mild Alzheimer's disease.

We investigated preserved episodic recognition memory based on incidental learning of visual associations in Alzheimer's disease (AD). In a cross-sectional design, we analyzed episodic memory score profiles of patients with amnestic mild cognitive impairment (a-MCI) (n = 42) or mild AD (n = 19) who had hippocampal atrophy, and healthy elderly controls (n = 43). The Visual Association Test-Extended served as a measure of episodic memory. Multiple-choice cued recognition was compared with paired associate recall and free recall within groups. Results showed that patients recognized learned material much better compared to when they had to recall material, resulting in large effect sizes (Cohen's d) ranging from 1.3 to 3.5. We conclude that episodic recognition memory based on incidental learning of visual associations is largely preserved when compared to recall in a-MCI and mild AD. This suggests that the episodic memory impairment in AD may be characterized as a retrieval impairment rather than a consolidation impairment, indicating that preserved recognition compared to recall may be compatible with AD being the correct diagnosis. Measuring the episodic memory impairment in AD may benefit from using tests that capture different aspects of memory processes such as incidental learning of visual associations.

Regression-Based Normative Data for the Montreal Cognitive Assessment (MoCA) and Its Memory Index Score (MoCA-MIS) for Individuals Aged 18-91.

(1) Background: There is a need for a brief assessment of cognitive function, both in patient care and scientific research, for which the Montreal Cognitive Assessment (MoCA) is a psychometrically reliable and valid tool. However, fine-grained normative data allowing for adjustment for age, education, and/or sex are lacking, especially for its Memory Index Score (MIS). (2) Methods: A total of 820 healthy individuals aged 18-91 (366 men) completed the Dutch MoCA (version 7.1), of whom 182 also completed the cued recall and recognition memory subtests enabling calculation of the MIS. Regression-based normative data were computed for the MoCA Total Score and MIS, following the data-handling procedure of the Advanced Neuropsychological Diagnostics Infrastructure (ANDI). (3) Results: Age, education level, and sex were significant predictors of the MoCA Total Score (Conditional R2 = 0.4, Marginal R2 = 0.12, restricted maximum likelihood (REML) criterion at convergence: 3470.1) and MIS (Marginal R2 = 0.14, REML criterion at convergence: 682.8). Percentile distributions are presented that allow for age, education and sex adjustment for the MoCA Total Score and the MIS. (4) Conclusions: We present normative data covering the full adult life span that can be used for the screening for overall cognitive deficits and memory impairment, not only in older people with or people at risk of neurodegenerative disease, but also in younger individuals with acquired brain injury, neurological disease, or non-neurological medical conditions.

Assessing neuropsychiatric symptoms in nursing home patients with dementia: reliability and Reliable Change Index of the Neuropsychiatric Inventory and the Cohen-Mansfield Agitation Inventory.

OBJECTIVE: The aim of the study was to estimate inter-observer and test-retest reliability of the Neuropsychiatric Inventory Nursing Home version (NPI-NH) and the Cohen-Mansfield Agitation Inventory (CMAI), and to establish their Reliable Change Index (RCI). Reliable Change methodology is a practical method for estimating the least change acquired in outcome measures. METHODS: Nursing home physicians and certified nurses assessed 105 patients with dementia (in five nursing homes) at baseline and after 2 weeks. Spearman rank correlations were calculated and Reliable Change Difference Scores (S(diff) (80)). RESULTS: NPI-NH inter-observer correlations ranged 0.14-0.70. NPI-NH test-retest correlations ranged 0.23-0.80. CMAI inter-observer correlations ranged -0.10 to 0.72. CMAI test-retest correlations ranged 0.32-1.00 (CMAI total score, ρ=0.89). S(diff) (80) for NPI-NH items ranged 1.7-5.0. A change of 11 points on the NPI-NH total score can be considered a true behavioral change. S(diff) (80) for CMAI total score was 8 and factor analysis based sub-scale scores physically aggressive behavior, physically non-aggressive behavior, and verbally agitated behavior were 3, 6, and 4, respectively. CONCLUSION: Reliability estimates and RCI for the NPI-NH were modest, seriously challenging its reliability and sensitivity to change over time. NPI-NH may only be useful for monitoring behavioral changes in individual patients with dementia, when symptoms are moderate to severe, or when effect sizes are large. Reliability of the CMAI was good, supporting its usefulness in clinical practice. Poor inter-observer agreement on behavioral observations poses a real challenge in nursing homes. Reliable scales are needed that include unambiguously formulated items.

Psychotropic drug prescription in nursing home patients with dementia: influence of environmental correlates and staff distress on physicians' prescription behavior.

BACKGROUND: The aim of the study was to examine whether staff distress and aspects of the nursing home environment were associated with psychotropic drug use (PDU) in patients with dementia. METHODS: This was a cross-sectional study of 1289 nursing home patients with dementia from 56 Dementia Special Care Units (SCUs) in the Netherlands. The primary outcome was PDU. Potential correlates of PDU were staff distress, environmental correlates (the number of patients per unit or per living room, staff/patient ratio, and the presence of a walking circuit), and patient factors (gender, age, dementia severity, and neuropsychiatric symptoms (NPS)). Multilevel logistic regression analysis was used to estimate the relative contributions of predictor variables in explaining PDU. RESULTS: Staff distress, aspects of the physical nursing home environment and patients' neuropsychiatric symptoms were independently associated with PDU. Staff distress at patients' agitation was associated with antipsychotic and anxiolytic drug use (OR 1.66, 95% CI (1.16-2.36) and 1.62 (1.00-2.61), respectively). SCUs with more patients per living room had higher hypnotic drug use (OR 1.08, 95% CI (1.02-1.14)). Low staff/patient ratio was associated with high antidepressant drug use (OR 0.13, 95% CI (0.04-0.47)). The effects of nursing home environment on study outcome were smallest for antidepressant use (intra-SCU correlation 0.005) and highest for hypnotic use (intra-SCU correlation 0.171). CONCLUSION: Staff distress and other environmental aspects are independently associated with PDU. These findings raise questions about the appropriateness of psychoactive drug prescriptions for nursing home patients with dementia.

Course of neuropsychiatric symptoms in residents with dementia in nursing homes over 2-year period.

OBJECTIVE: To determine the course of neuropsychiatric symptoms (NPSs) in nursing home residents with dementia and to determine their variability across diagnosis. DESIGN: Prospective cohort study over 2 years. SETTING: Fourteen dementia special care units in nine nursing homes in The Netherlands. PARTICIPANTS: One hundred seventeen residents with dementia. MEASUREMENTS: NPSs were measured using the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). RESULTS: The majority of residents had moderately severe to severe dementia. All but a few residents (97%) showed any NPS, and co-occurrence of NPSs was high. Agitation, irritability, and aberrant motor behavior were the most prevalent over the 2 years. Depression and anxiety as well as NPI total score decreased over time, whereas apathy tended to increase. Agitation and aberrant motor behavior were the most persistent symptoms. In asymptomatic residents, highest incidence rates were found for apathy, aggression/ agitation, irritability, and aberrant motor behavior. Anxiety and apathy were more prevalent in Alzheimer disease (AD) compared with vascular disease (VaD); vice versa, aggression and depression were more prevalent in VaD. Differences in change over time between AD and VaD were found for irritability and disinhibition. CONCLUSION: This is the first study examining the 2-year course of NPSs in a large group of nursing home residents with dementia. Virtually all residents demonstrated and/or developed NPSs. Although affective symptoms decreased, apathy tended to increase. Agitated behaviors were particularly persistent. Our data may contribute to improve mental healthcare for demented nursing home residents.

Environmental correlates of neuropsychiatric symptoms in nursing home patients with dementia.

OBJECTIVE: The aim of the study was to estimate the influence of environmental correlates of neuropsychiatric symptoms in nursing home patients with dementia. METHODS: 1289 patients in 56 Dementia Special Care Units (SCUs) in the Netherlands were assessed using the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) and the Cohen-Mansfield Agitation Inventory (CMAI). Potential correlates of the neuropsychiatric symptoms studied were gender and age of the patient, dementia severity, psychoactive medication use and environmental correlates such as the number of patients per unit or per living room, staff size/patient ratio, time spent on care activities and presence of a walking circuit. Multilevel logistic regression analysis was used to estimate the relative contribution of the different factors in explaining neuropsychiatric symptoms variability. RESULTS: The prevalence of neuropsychiatric symptoms differed between SCUs, also after correcting for patient factors. Patient-related factors explained 7-21% of the total variance of neuropsychiatric symptoms. Intra Class Correlation (the correlation of symptoms of patients within SCUs) ranged from 0.039 (psychosis) to 0.163 (apathy). The variance in SCU symptom prevalence (variance between SCUs) accounted for 3.5-14.8% of the total variance in neuropsychiatric symptoms. In SCUs of which the staff spent more time on care activities did the patients show lower levels of apathy. Other environmental correlates did not predict neuropsychiatric symptoms. CONCLUSION: The substantial variation of prevalence rates between SCUs in combination with the clustering of symptoms within SCUs is strong evidence for the environmental contribution to neuropsychiatric symptoms and the multifactorial nature of behaviour in dementia.

Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis.

CONTEXT: Delirium is a common and serious complication in elderly patients. Evidence suggests that delirium is associated with long-term poor outcome but delirium often occurs in individuals with more severe underlying disease. OBJECTIVE: To assess the association between delirium in elderly patients and long-term poor outcome, defined as mortality, institutionalization, or dementia, while controlling for important confounders. DATA SOURCES: A systematic search of studies published between January 1981 and April 2010 was conducted using the databases of MEDLINE, EMBASE, PsycINFO, and CINAHL. STUDY SELECTION: Observational studies of elderly patients with delirium as a study variable and data on mortality, institutionalization, or dementia after a minimum follow-up of 3 months, and published in the English or Dutch language. Titles, abstracts, and articles were reviewed independently by 2 of the authors. Of 2939 references in the original search, 51 relevant articles were identified. DATA EXTRACTION: Information on study design, characteristics of the study population, and outcome were extracted. Quality of studies was assessed based on elements of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies. DATA SYNTHESIS: The primary analyses included only high-quality studies with statistical control for age, sex, comorbid illness or illness severity, and baseline dementia. Pooled-effect estimates were calculated with random-effects models. The primary analysis with adjusted hazard ratios (HRs) showed that delirium is associated with an increased risk of death compared with controls after an average follow-up of 22.7 months (7 studies; 271/714 patients [38.0%] with delirium, 616/2243 controls [27.5%]; HR, 1.95 [95% confidence interval {CI}, 1.51-2.52]; I(2), 44.0%). Moreover, patients who had experienced delirium were also at increased risk of institutionalization (7 studies; average follow-up, 14.6 months; 176/527 patients [33.4%] with delirium and 219/2052 controls [10.7%]; odds ratio [OR], 2.41 [95% CI, 1.77-3.29]; I(2), 0%) and dementia (2 studies; average follow-up, 4.1 years; 35/56 patients [62.5%] with delirium and 15/185 controls [8.1%]; OR, 12.52 [95% CI, 1.86-84.21]; I(2), 52.4%). The sensitivity, trim-and-fill, and secondary analyses with unadjusted high-quality risk estimates stratified according to the study characteristics confirmed the robustness of these results. CONCLUSION: This meta-analysis provides evidence that delirium in elderly patients is associated with poor outcome independent of important confounders, such as age, sex, comorbid illness or illness severity, and baseline dementia.

Predictors of neuropsychiatric symptoms in nursing home patients: influence of gender and dementia severity.

INTRODUCTION: The aim of the study was to assess the influence of dementia severity and gender on neuropsychiatric symptoms in demented nursing home patients. METHODS: Neuropsychiatric symptoms were assessed in a large sample of 1319 Dutch nursing home patients using the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). The influence of gender and severity of cognitive decline, assessed with the Global Deterioration Scale (GDS), was investigated using logistic regression analysis and subsequently corrected for possible confounders, such as age, duration of institutionalization and psychoactive medication use. RESULTS: While physically aggressive behaviour was more common in patients with very severe cognitive deterioration (GDS stage 7), disinhibition, irritability, physically non-aggressive and verbally agitated behaviour were more common in patients in GDS stage 5 or 6. Physically aggressive behaviour was more common in men, whereas female patients demonstrated more verbally agitated behaviour. With respect to other neuropsychiatric symptoms, delusions and depression were also more common in patients in GDS stage 5 and 6, while prevalences of anxiety and apathy further increased in severely demented patients (GDS stage 7). Apathy was more prevalent in male patients, while depression and anxiety were more common in females. CONCLUSION: In nursing home patients, neuropsychiatric symptoms were associated with the severity of dementia, with most symptoms occurring in patients showing (moderately) severe cognitive decline. Only physical aggression, anxiety and apathy were more common in patients with very severe cognitive decline. Dementia severity and gender were important predictors of neuropsychiatric symptoms in this patient cohort.

Testing Episodic Memory in Elderly Subjects: Not as Simple as It Looks.

BACKGROUND/AIMS: The available episodic memory tests are not specifically constructed to examine older subjects. Their use in outpatient memory clinics may result in aborted test administration. We used a strict adherence to the test protocol in cognitively healthy, amnestic mild cognitive impairment (aMCI), and Alzheimer's disease dementia subjects to assess the possibility of preventing this. METHODS: This is a cross-sectional study in memory outpatient subjects with a mean age of 74.5 years. Primary study outcomes were: number of missing values and test results in the Visual Association Test (VAT) and the 15 Word Test (15WT). RESULTS: A strict adherence to the test protocol resulted in a 10-fold decrease in the number of missing values in the VAT. For the 15WT this could not be realized mostly because the test was deemed too demanding for 1 in 6 patients. CONCLUSIONS: This study is one of the few examining the applicability of well-known episodic memory tests in older subjects. A strict adherence to the test protocol reduced the number of missing values. Floor effects were stronger for the 15WT than for the VAT. Results favor the use of the VAT in senior subjects and show the unsuitability of the 15WT in this group.

Visual associations to retrieve episodic memory across healthy elderly, mild cognitive impairment, and patients with Alzheimer's disease.

Episodic memory tests need to determine the degree to which patients with moderate to severe memory deficits can still benefit from retrieval support. Especially in the case of Alzheimer's disease (AD), this may support health care to be more closely aligned with patients' memory capacities. We investigated whether the different measures of episodic memory of the Visual Association Test-Extended (VAT-E) can provide a more detailed and informative assessment on memory disturbances across a broad range of cognitive decline, from normal to severe impairment as seen in AD, by examining differences in floor effects. The VAT-E consists of 24 pairs of black-and-white line drawings. In a within-group design, we compared score distributions of VAT-E subtests in healthy elderly controls, mild cognitive impairment (MCI), and AD (n = 144), as well as in relation to global cognitive impairment. Paired associate recall showed a floor effect in 41% of MCI patients and 62% of AD patients. Free recall showed a floor effect in 73% of MCI patients and 84% of AD patients. Multiple-choice cued recognition did not show a floor effect in either of the patient groups. We conclude that the VAT-E covers a broad range of episodic memory decline in patients. As expected, paired associate recall was of intermediate difficulty, free recall was most difficult, and multiple-choice cued recognition was least difficult for patients. These varying levels of difficulty enable a more accurate determination of the level of retrieval support that can still benefit patients across a broad range of cognitive decline.

Long-term cognitive outcome of delirium in elderly hip surgery patients. A prospective matched controlled study over two and a half years.

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