The current therapeutic agents advocated for the treatment of delirium (Meagher, 2001) have not been developed from an understanding of the underlying pathophysiology of this condition. Rather, they have emerged from “off label” clinical practice which has sought to reduce the distress experienced by both patients and clinicians. Accordingly, their use has not developed from a strong, specific evidence base, and nor is it now supported by large, well-designed clinical trials. It is also the case that these drug treatments will address the management (usually by sedation) of patients with florid, psychotic or “positive” delirium whilst quiet or “negative” delirium remains under-diagnosed and is poorly managed despite the distress it causes patients.

Introduction: The aim of this study is to understand the long-term course and outcomes of depressive symptoms among older adults in the community by examining trajectories of depressive symptoms over time and identifying profiles of depressive symptoms predicting different trajectories.

Method: We measured depressive symptoms biennially for up to 12 years, using the modified Center for Epidemiological Studies-Depression (mCES-D) scale, in 1260 community-based adults aged 65+ years. We determined latent trajectories of total mCES-D scores over time. We identified symptom profiles based on subgroups of baseline depressive symptoms derived from factor analysis, and examined their associations with the different trajectories.

Results: Six trajectories were identified. Two had one or no depressive symptoms at baseline and flat trajectories during follow-up. Two began with low baseline symptom scores and then diverged; female sex and functional disability were associated with future increases in depressive symptoms. Two trajectories began with high baseline scores but had different slopes: the higher trajectory was associated with medical burden, higher overall baseline score, and higher baseline scores on symptom profiles including low self-esteem, interpersonal difficulties, neurovegetative symptoms, and anhedonia. Mortality was higher among those in the higher trajectories.

Conclusions: In the community at large, those with minimal depressive symptoms are more likely to experience future increases in symptoms if they are women and have functional disability. Among those with higher current symptom levels, depression is more likely to persist over time in individuals who have greater medical burden and specific depressive symptoms.

Background: We evaluated the combined and differential effects of physical, social and productive activities on cognitive decline and whether they were modified by the presence of the APOE-ε4 allele.

Methods: In a prospective cohort study of 1635 community-dwelling Chinese older adults aged 55 or older participating in the ongoing Singapore Longitudinal Aging Study, physical, social and productive leisure activities were assessed at baseline, and cognitive decline (at least one point drop) in MMSE scores between baseline and follow-up after one year.

Results: Cognitive decline was observed in 30% of the respondents. Controlling for age, gender, education and other risk factors, odds ratios (ORs) were significantly reduced in those with medium (OR: 0.60, 95% CI: 0.45–0.79) and high activity levels (OR: 0.62, 95% CI: 0.46–0.84). A stronger association was shown for productive activity (OR = 0.36), than for physical (OR = 0.78) and social activities (OR = 0.85). These associations showed statistically significant interactions with APOE genotype, being more pronounced in those with the APOE-ε4 allele.

Conclusion: Increased leisure activity, especially productive activities more than physical or social activities, was associated with a lowered risk of cognitive decline. APOE-ε4 genotype individuals appeared to be more vulnerable to the effects of low and high levels of leisure activities.

Objective: Clinical syndromes such as amnestic mild cognitive impairment (MCI) are highly predictive of future development of Alzheimer's disease (AD), but it is not known how many of the individuals that develop the disease can be identified with these syndromes. This study aims to determine how many individuals with AD show detectable symptoms or clinical signs of cognitive deficits three years before diagnosis.

Methods: 152 incident AD cases were identified in a dementia-free cohort of 1417 persons aged 75–95, after three-year follow-up from a prospective population-based study, the Kungsholmen Project. Symptoms of cognitive impairment including the subjective report of memory problems, and cognitive deficits were objectively measured with an extensive neuropsychological test battery at baseline. Incident AD was clinically diagnosed according to DSM-IIIR criteria at three-year follow-up.

Results: Only half of future AD cases reported subjective memory problems three years before diagnosis. More than one-third of incident AD cases did not exhibit detectable deficits in any of the investigated specific cognitive domains. Only 38.3% had both subjective complaints and domain-specific cognitive deficits.

Conclusions: Symptoms and signs currently used to define MCI are not always present in persons who develop AD. Increasing the number of potentially identifiable and treatable preclinical AD cases is unfeasible unless more sensitive subjective and objective markers are identified. Furthermore, as only half of future AD cases report subjective memory problems three years before diagnosis, the number of persons coming to the attention of medical care is limited.

Over 20 years ago the publication of an optimistic report by Summers and colleagues (1986) on the use of the cholinesterase inhibitor tetrahydroaminoacridine (THA/tacrine) to treat patients affected by Alzheimer's disease (AD) started an avalanche of research publications on the use of cholinesterase inhibitors for the symptomatic treatment of the cognitive deficits seen in people with AD. Despite the fact that the Summers et al. study turned out to be very deeply flawed indeed (Division of Neuropharmacological Drug Products, 1991), the juggernaut whose movement it initiated has not yet ceased to roll. Subsequent large studies of tacrine performed on people with carefully diagnosed AD established a plausible methodology for the conduct of clinical studies of drug efficacy in the treatment of AD (Ritchie et al., 2007). These studies suggested that the drug had modest beneficial effects in some patients (Ritchie et al., 2007), and revealed that it had a high rate of adverse effects on the gut (Brodaty, 1996) and liver (Ames et al., 1990).

There is broad agreement that randomized controlled double-blind trials (RCTs) do reveal only small effects of the cholinesterase inhibitors donepezil, rivastigmine and galantamine in the treatment of Alzheimer's disease (AD) (Perras et al., 2005; Cummings et al., 2002; Schneider, 2004). Furthermore, it is controversial whether the small effects shown in the RCTs are reliable or due to bias. In 2005 we published a systematic review of all RCTs on cholinesterase inhibitors which came to the conclusion that the scientific basis for a general recommendation of cholinesterase inhibitors in the treatment of AD is questionable because of the methodological shortcomings of the studies (Kaduszkiewicz et al., 2005). Following numerous debates on this topic at congresses and enriched through reviews of the U.K. National Institute for Health and Clinical Excellence (NICE, 2006) and the German Institute for Quality and Efficiency in Health Care (IQWiG, 2007), we will here present our actual view on this controversy. The main part of this article focuses on the methodology of cholinesterase inhibitor trials and on the interpretation of their results. We conclude by discussing briefly the three Cochrane reviews on cholinesterase inhibitors for AD.

The cholinesterase inhibitors (tacrine, donepezil, galantamine and rivastigmine) were the first drugs licensed for mild to moderate Alzheimer's disease (AD). Recently, the use of donepezil has been extended to severe AD. Tacrine was the first to be marketed, which, although beneficial in AD, shows a high incidence of adverse effects and is rarely used. It will not be discussed further. The cholinesterase inhibitors are widely prescribed and continue to be the first line in the treatment of AD. Considering the mode of action of the cholinesterase inhibitors it is not expected that they will alter the course of the disease, but they may help with some of the manifestations of dementia.

The emergence of evidence-based medicine has challenged many conventional ideas about medical research. Instead of focusing just on individual studies, a science of systematic reviews has evolved. The Cochrane Collaboration, still only 15 years old, aims to collate systematically all randomized controlled trials through regularly updated systematic reviews to provide the best current evidence on different therapies. The most recent update has over 3000 reviews and over 1700 more protocols registered. Many expected that methodologically rigorous systematic reviews would bring clarity and agreement on the evidence for each therapy, so at first sight the disagreements between Kaduszkiewicz et al. and Birks seem surprising.

David Ames has undertaken research with cholinesterase inhibitor drugs supported by Eisai, Janssen, Parke-Davis and Pfizer. He has received honoraria for talks and consultancies and some financial support to enable conference attendance from those four companies and from Novartis, the other pharmaceutical company to market a cholinesterase inhibitor in Australia.

Objective: To review and summarize the currently available data on the use of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate) in the treatment of behavioral and psychological symptoms of dementia (BPSD); to determine whether these medications can be recommended for routine clinical use.

Methods: Literature search in five databases (PubMed, MEDLINE, EMBASE, PsychINFO and COCHRANE collaboration) and analysis of the randomized controlled double-blinded clinical trials found therein.

Results: A total of seven RCTs were identified (two for carbamazepine and five for valproate). One study showed statistically significant improvement of BPSD in the medication group in comparison to the placebo group; five studies showed no significant differences; one study showed statistically significant worsening of the symptoms in the medication group vs. placebo. The majority of the studies reported significantly more frequent adverse effects in the medication group.

Conclusion: Although clearly beneficial in some patients, anticonvulsant mood stabilizers cannot be recommended for routine use in the treatment of BPSD at the present time.

Background: Rapid response to antidepressant therapy is desirable and may be particularly critical in elderly patients with major depressive disorder (MDD).

Methods: Findings are based on post-hoc analyses from a double-blind trial of elderly patients with MDD ≥ 65 years, randomly assigned 2:1 to duloxetine 60 mg QD (N = 207) or placebo (N = 104) for 8 weeks. Depression and pain measures included the Geriatric Depression Scale (GDS), 17-item Hamilton Depression Scale (HAMD17), CGI-Severity, and Visual Analog Scale (VAS) for overall pain. The time to response and remission for duloxetine compared with placebo was evaluated using Cox proportional hazards (PH) modeling, Kaplan-Meier estimation, and categorical repeated measures analysis.

Results: Significant improvements of estimated HAMD17 response and remission rates for duloxetine started at week 2 (P = 0.022 and P = 0.033, respectively). Time to HAMD17 response and remission were significantly shorter for duloxetine versus placebo (P < 0.001 and P = 0.004, respectively). Placebo-referenced duloxetine hazard ratios (HR) for HAMD17 response and remission were 2.03 (P = 0.002) and 2.01 (P = 0.006), respectively. Results for GDS-based response (HR = 1.54, P = 0.023) and remission (HR = 1.54, P = 0.104) rates were consistent with the HAMD17 findings. Patients ≥75 years (n = 93) responded with similar rapidity to duloxetine compared with those <75 years (n = 199, P > 0.10 for all PH treatment-by-age interactions). The placebo-referenced duloxetine HR for time to 50% reduction in overall pain was 1.75 (P = 0.024) for patients with moderate to severe pain.

Conclusion: Duloxetine demonstrated a faster time to antidepressant response and improvement in self-reported pain as compared with placebo.

Clinical trial registry number for this study: NCT00062673, at www.clinicaltrials.gov.

Background: Apathy is defined as lack of motivation and occurs in a variety of neuropsychological disorders. The Apathy Evaluation Scale (AES) has been shown to be valid and reliable for assessing apathy in depression but the validity and reliability of the Chinese version has never been examined. The aims of the study were to (1) evaluate the validity and reliability of the Chinese version of the AES in late-life depression and (2) evaluate the severity of apathy in late-life depression.

Methods: We translated the AES into Chinese and used a cross-sectional design to evaluate apathy in elderly subjects. Diagnostic and Statistical Manual of Mental Disorders (DSM) -IV criteria and Hamilton Depression Rating Scale (HDRS) were applied for diagnosis and assessment. Three groups of subjects were recruited including one group (n = 31) of patients with major depressive disorder with current depression, the second group (n = 30) with major depressed disorder with remission, and the third group (n = 31) of healthy controls. Convergent validity was tested using four apathy-related items from the HDRS (loss of interest, psychomotor retardation, loss of energy, and loss of insight). Multiple forms of reliability (including internal consistency, test-retest, and interrater) and discriminant validity were examined.

Results: We demonstrated that the internal consistency (coefficient α = 0.90) and test-retest reliability (p < 0.001) were satisfied. Discriminant validity of apathy severity among these three groups was significant. The convergent validity and correlation coefficients based on the four apathy-related items from the HDRS and AES were acceptable.

Conclusion: Apathy is a distinct syndrome which may be treatable when depression is effective managed. Further application of the Chinese version of the AES to study the association of apathy with other neuropsychological symptoms is necessary.

Introduction: Studies in the West have concluded that the severity of depression is the strongest predictor of the course of suicidal ideations among the elderly. However, Asian culture tends to be more reserved and this may impact on the reporting of suicidal ideations. This study aims to determine the prevalence of suicidal ideation among depressed elderly people in Singapore and attempts to investigate the relationship between severity of depression and suicidality.

Method: Eighty consecutive depressed patients were recruited and severity of depressive symptoms rated with Beck's Depression Inventory (BDI). Suicidality was assessed using the Beck's Hopelessness Scale (BHS) and Beck's Suicide Intent Scale (BSS). Suicidal ideation was defined as any thought of wanting to kill oneself over the past seven days and not just a passive wish to die.

Results: 53.8% verbalized thoughts of wanting to kill themselves. Males were three times more likely to report suicidal thoughts. Severity of depression did not significantly influence the presence of suicidal thinking. The association of depression severity and suicidal ideations is not strongly supported.

Conclusions: Elderly males were more likely to report suicidal ideations when depressed. Elderly patients who reported suicidal ideations were likely to be more severely depressed. However, in a depressed elderly person, the absence of suicidal ideations would not infer that the episode of depression was less severe.

Background: Socioeconomic status may influence cross-national variations in elderly suicide rates.

Methods: The relationship between suicide rates in both sexes in the age-bands 65–74 years and 75+ years and (i) life expectancy, (ii) measures of socioeconomic status (per capita gross national domestic product (GDP) and the Gini coeffcient), and (iii) measures of the quality and quantity of available healthcare services (the proportion of GDP spent on health, per capita expenditure on health and child mortality rates) was examined using data from the World Health Organization and the United Nations.

Results: The main findings were: (i) a significant negative correlation between the Gini coefficient and suicide rates for both sexes in both age-bands; (ii) a significant positive correlation between per capita expenditure on health and suicide rates for both sexes in both age-bands; (iii) the significant positive correlation between the proportion of GDP spent on health and suicide rates was only evident in males in both age-bands; (iv) a significant negative correlation between child mortality rates and suicide rates for both sexes in both age-bands; and, (v) the significant positive correlation between life expectancy and suicide rates was evident in females in both age-bands.

Conclusions: A potentially testable model with five sequential stages was proposed to explain these findings.

Background: Nursing care for people with dementia diseases affecting the frontal lobes places special demands on staff, but there is little information available about how best to tailor nursing care. The aim of this study was to describe nurses' experience of difficulties and possibilities in caring for people with dementia diseases with frontal-lobe dysfunction.

Method: The study was carried out as a descriptive qualitative study. Data collected during interviews with nursing staff (n = 10) were analyzed using qualitative content analysis.

Results: The difficulties experienced were related to the patients' lack of inhibition and judgment, anxiety, agitation, reduced ability to deal with physical needs, egocentricity, imbalance between rest and activity and depressed mood. The possibilities were seen in relation to the nursing staff's professional encounters, characterized as being clear and consistent, a step ahead, flexible, calm and creating a positive atmosphere, close and trusting and being and doing things together. Continuous feedback and support were prerequisites for the engagement of the staff.

Conclusion: Nursing care in this context involves ethical issues whereby the residents' integrity must be balanced against a safe and secure environment. Nursing care is a sensitive but also demanding task, where nurses' actions can reduce the negative effects of the disease. It is therefore important to support staff in nursing care so they are able to manage their work and reduce the risk of emotional exhaustion.

Background: Psychiatric symptoms and behavioral disturbances are highly prevalent in the residents of nursing homes. The Neuropsychiatric Inventory (NPI) is a commonly used scale for the assessment of such symptoms in diverse settings. We have conducted a study of the reliability and the validity of the Norwegian version of the NPI nursing home version (NPI-NH).

Methods: The reliability study comprised 41 patients. We established inter-rater reliability between raters with various levels of health education using κ statistics. Fifty patients were included in the validity study. The patients were examined by a physician, who also rated the patient's behavior using “behavioral pathology in Alzheimer's disease” (BEHAVE-AD). Subsequently, a research nurse performed a standardized interview using the NPI and the Cornell scale. Concurrent validity of the NPI and the BEHAVE-AD was analyzed.

Results: Internal consistency, as measured by Cronbach's α was above 0.8. Inter-rater reliability was, except for one item, between 0.85 and 1.0 across assessors with different levels of health education. All correlations between the NPI and the BEHAVE-AD were significant, ranging from 0.38 to 0.72. The weakest correlations were between items assessing affective and anxiety symptoms.

Conclusion: The Norwegian version of the NPI-NH is a reliable and valid instrument for assessing psychiatric symptoms and behavioral disturbances in the residents of nursing homes. The investigation of depressive symptoms merits particular attention.

Background: Behavioral symptoms and caregivers' responses may differ among various ethnic and cultural groups. Therefore it is important to have a reliable instrument to assess behavioral disturbances of dementia in various cultures. The Neuropsychiatric Inventory (NPI) has been widely used in many countries. To date there has been no reliability study of this instrument in Brazil.

Methods: The psychometric properties of the Brazilian Portuguese version of the NPI were studied in a sample of 36 Alzheimer's disease (AD) outpatients from southern Brazil. Test-retest, inter-rater reliability and internal consistency were estimated. The profile of neuropsychiatric symptoms and caregiver distress were also evaluated. The NPI was translated into Portuguese and then back translated to English.

Results: The Brazilian Portuguese version of the NPI showed good inter-rater and test-retest reliability with the coefficients of all scales > 0.85. Internal consistency was also good (Cronbach's α 0.70 for total severity and distress). Apathy provided higher NPI scores of total severity and distress.

Conclusions: This NPI version was found to be a reliable instrument for the evaluation of neuropsychiatric symptoms and caregiver distress due to dementia in AD. The profile of behavioral disturbances was similar to that observed in other countries. Severity of dementia may have biased some caregivers' answers.

Background: The aim of this study was to determine the prevalence of dementia in a socioeconomically disadvantaged population of older adults living in the city of São Paulo, Brazil.

Methods: A cross-sectional one-phase population-based study was carried out among all residents aged ≥ 65 in defined census sectors of an economically disadvantaged area of São Paulo. Identification of cases of dementia followed the protocol developed by the 10/66 Dementia Research Group.

Results: Of 2072 individuals in the study, 105 met the criteria for a diagnosis of dementia, yielding a prevalence of 5.1%. Prevalence increased with age for both men and women after age 75 years, but was stable from 65 to 74 years. Low education and income were associated with increased risk of dementia.

Conclusions: The prevalence of dementia among older adults from low socioeconomic backgrounds is high. This may be partly due to adverse socioeconomic conditions and consequent failure to compress morbidity into the latter stages of life. The increasing survival of poorer older adults with dementia living in developing countries may lead to a rapid increase in the prevalence of dementia worldwide.

Background: Dementia differs from other terminal illnesses both in its slow progression and the fact that patients and family members often do not perceive it as a cause of death. Furthermore, because decisional incapacity is almost universal in patients with advanced dementia, decisions must be made by surrogates. However, little is known about the factors that influence how surrogates make decisions for persons with late-stage dementia.

Methods: The setting was the first wave of a study of patients with advanced dementia in three Maryland nursing homes (The Care of Nursing Home Residents with Advanced Dementia Study). Of 125 consented participants, 123 residents and their surrogates provided adequate information and agreed to interviews and medical record reviews. Bivariate analysis and logistic regression models were used to explore whether variables related to demographics, illness, communication and surrogate background were associated with surrogate decisions to not provide aggressive treatments (i.e. hospitalization or surgery).

Results: Treatment decisions regarding aggressive medical care had been made by 81% of surrogates over the preceding 6 months. In bivariate analysis the following factors were significantly associated with not providing aggressive care: resident and surrogate of white race, older surrogate age, worse resident medical illness, worse surrogate perception of resident quality of life, presence of a ‘do not hospitalize’ order (DNH), and more contact with nurses. In the multivariate analysis, resident white race and presence of a DNH were significant predictors of surrogate decisions to not provide aggressive treatments. Treatment decisions were not associated with surrogate relationship or religiosity.

Conclusions: Treatment decisions for individuals with advanced dementia are mostly strongly associated with the patient's race and presence of DNH and less so with changeable features of illness or environment.