Background: The study aim was to conduct a systematic review of the evidence from randomized, placebo controlled trials related to the efficacy of donepezil, rivastigmine and galantamine in the treatment of behavioral and psychological symptoms of Alzheimer's disease.

Methods: Electronic database searches of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were carried out using multiple search terms. Articles included were original publications of randomized, placebo-controlled trials of monotherapy of donepezil, rivastigmine or galantamine that reported a behavioral outcome measure.

Results: 14 studies were identified that matched inclusion criteria. Nine were of donepezil, three of galantamine and two of rivastigmine. Median study treatment length was 24 weeks (range 12–170). Most studies used the Neuropsychiatric Inventory as a behavioral outcome measure although three used specific scales for either agitation or apathy. Four studies were specifically designed to assess behavioral outcomes whilst in the majority of studies behavioral outcomes were only secondary measures. Three studies found statistically significant, albeit modest, differences in the change of NPI total score between drug and placebo. The interpretation of the results of many studies is limited by methodological considerations, including generally low NPI scores at baseline and the investigation of behavioral and psychological symptoms of dementia (BPSD) as secondary outcomes.

Conclusions: The evidence base regarding the efficacy of cholinesterase inhibitors in BPSD is limited, in part due to methodological considerations. In the absence of alternative safe and effective management options, the use of cholinesterase inhibitors is an appropriate pharmacological strategy for the management of BPSD in Alzheimer's disease.

Objectives: To estimate the annual rate of change scores (ARC) on the Mini-Mental State Examination (MMSE) in Alzheimer's disease (AD) and to identify study or population characteristics that may affect the ARC estimation. Methods: MEDLINE was searched for articles published from January 1981 to November 1997 using the following keywords: AD and longitudinal study or prognosis or cognitive decline. The bibliographies of review articles and relevant papers were searched for additional references. All retrieved articles were screened to meet the following inclusion criteria: (a) original study; (b) addressed cognitive decline or prognosis or course of AD; (c) published in English; (d) study population included AD patients with ascertainable sample size; (e) used either clinical or pathological diagnostic criteria; (f) longitudinal study design; and (g) used the MMSE as one of the outcome measures. Data were systematically abstracted from the included studies, and a random effects regression model was employed to synthesize relevant data across studies and to evaluate the effects of study methodology on ARC estimation and its effect size. Results: Of the 439 studies screened, 43 met all the inclusion criteria. After 6 studies with inadequate or overlapping data were excluded, 37 studies involving 3,492 AD patients followed over an average of 2 years were included in the meta-analysis. The pooled estimate of ARC was 3.3 (95% confidence interval [CI]: 2.9-3.7). The observed variability in ARC across studies could not be explained with the covariates we studied, whereas part of the variability in the effect size of ARC could be explained by the minimum MMSE score at entry and number of assessments. Conclusions: A pooled average estimate of ARC in AD patients was 3.3 points (95% CI: 2.9-3.7) on the MMSE. Significant heterogeneity of ARC estimates existed across the studies and cannot be explained by the study or population characteristics investigated. Effect size of ARC was related to the initial MMSE score of the study population and the number of assessments.

Objective: To provide a systematic review of selected experimental studies of psychosocial treatments of behavioral disturbances in dementia. Psychosocial treatments are defined here as strategies derived from one of three psychologically oriented paradigms (learning theory, unmet needs and altered stress thresholds).

Method: English language reports published or in press by December 2006 were identified by means of database searches, checks of previous reviews and contact with recognized experts. Papers were appraised with respect to study design, participants' characteristics and reporting details. Because people with dementia often respond positively to personal contact, studies were included only if control conditions entailed similar levels of social attention or if one treatment was compared with another.

Results: Only 25 of 118 relevant studies met every specification. Treatment proved more effective than an attention control condition in reducing behavioral symptoms in only 11 of the 25 studies. Effect sizes were mostly small or moderate. Treatments with moderate or large effect sizes included aromatherapy, ability-focused carer education, bed baths, preferred music and muscle relaxation training.

Conclusions: Some psychosocial interventions appear to have specific therapeutic properties, over and above those due to the benefits of participating in a clinical trial. Their effects were mostly small to moderate with a short duration of action. This limited action means that treatments will work best in specific, time-limited situations. In the few studies that addressed within-group differences, there were marked variations in response. Some participants benefited greatly from a treatment, while others did not. Interventions proved more effective when tailored to individuals' preferences.

Background: Anxiety and depression are common in older people but are often missed; to improve detection we must focus on those elderly people at risk. Frailty is a geriatric syndrome inferring increased risk of poor outcomes. Our objective was to explore the relationship between frailty and clinically significant anxiety and depression in later life.

Methods: This study had a cross-sectional design and involved the assessment of 567 community-dwelling people aged ≥60 years recruited from the Technology Research for Independent Living (TRIL) Clinic, Dublin. Frailty was measured using the Fried biological syndrome model; depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale; and anxiety symptoms measured using the Hospital Anxiety and Depression Scale.

Results: Higher depression and anxiety scores were identified in both pre-frail and frail groups compared to robust elders (three-way factorial ANOVA, p ≤0.0001). In a logistic regression model the odds ratio for frailty showed a significantly higher likelihood of clinically meaningful depressive and anxiety symptoms even controlling for age, gender and a history of depression or anxiety requiring pharmacotherapy (OR = 4.3; 95% CI 1.5, 11.9; p = 0.005; OR = 4.36; 95% CI 1.4, 13.8; p = 0.013 respectively).

Conclusions: Our findings suggest that even at the earliest stage of pre-frailty, there is an association with increased symptoms of emotional distress; once frailty develops there is a higher likelihood of clinically significant depression and anxiety. Frailty may be relevant in identifying older people at risk of deteriorating mental health.

Background: Agitation is common in people with dementia, is distressing to patients and stressful to their carers. Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate. Alternatives to drug treatment for agitation should be sought. The study aimed to assess the effects of bright light therapy on agitation and sleep in people with dementia.

Methods: A single center randomized controlled trial of bright light therapy versus standard light was carried out. The study was completed prior to the mandatory registration of randomized controls on the clinical trials registry database and, owing to delays in writing up, retrospective registration was not completed.

Results: There was limited evidence of reduction in agitation in people on active treatment, sleep was improved and a suggestion of greater efficacy in the winter months.

Conclusions: Bright light therapy is a potential alternative to drug treatment in people with dementia who are agitated.

Background: Normal aging and dementia are characterized by increased prevalence of sleep disorders and alterations of both sleep continuity and architecture. However, little is still known about the nature of sleep in mild cognitive impairment (MCI), which is presumably situated on the continuum from healthy aging to dementia. This unsystematic review summarizes the current literature on the prevalence and severity of sleep disturbances in MCI.

Methods: Eighteen studies addressing sleep/night-time disturbances among other neuropsychiatric symptoms in individuals with MCI were identified through a search of databases and an examination of reference lists of selected papers. Fifteen of those studies reported data on prevalence or severity of sleep/night-time disturbances.

Results: Results indicated that 14–59% of patients with MCI had sleep disturbances. These disturbances were often identified as one of the four most prevalent neuropsychiatric symptoms of MCI and were considered as clinically significant in some studies. In addition, there was some evidence that the prevalence of sleep disturbances in MCI is intermediate between that of normal aging and dementia. Longitudinal data suggest that sleep problems are associated with both incident MCI and dementia.

Conclusions: These findings support the hypothesis that sleep disturbances are one of the core non-cognitive symptoms of MCI. It remains to be known whether sleep problems could help to identify those individuals with MCI who will eventually develop dementia. Studies characterizing sleep more systematically are needed to verify this proposition and to clarify the associations between sleep disturbances and other neuropsychiatric symptoms of MCI.

Background: This study examines predictors of loneliness among low-income older adults through a framework named MODEL (Model of Depression and Loneliness), which we developed to address the need for a comprehensive and intervention-oriented theory of loneliness in old age. The framework is rooted in a cognitive-behavioral theory that conceptualizes behaviors as resulting from an interaction of cognitive processes and environmental events.

Methods: 161 residents of five independent-living buildings for low-income older adults in Maryland were interviewed individually. The assessments were based on the theoretical framework, MODEL, which describes the influences that environmental resources, health, and psychological factors have on loneliness and depression.

Results: MODEL explained a large percentage of the variance of both loneliness and depressed affect. Of all the barriers examined in the present study, our findings suggest that psychosocial factors/barriers have the strongest influence in the etiology of loneliness.

Conclusion: In this population of low-income older persons, the importance of new contacts, mobility, and financial resources in predicting loneliness suggests that preventive social services should target these factors in developing opportunities for socialization.

Background: Few people with dementia have made advance plans for their health care. Advance care planning (ACP) is a process of discussion between an individual and their care providers that takes account of wishes and preferences for future care. We aimed to examine the facilitators and inhibitors to ACP in people with dementia. We also aimed to identify key themes in the literature and critically review the methodologies used.

Methods: We systematically searched the English language literature including PubMed, CINAHL, AMED, PsychINFO, EMBASE and BNI. We included empirical studies which reported the characteristics of the patient population, the type of advance care planning used and the study setting, and which involved people with dementia, family members or professional carers.

Results: We identified 17 studies (11 quantitative methods, one qualitative and five mixed methods). We found one ACP intervention which changed outcomes for people with dementia. Key themes were identified: there is a point at which cognition decreases critically so that an advanced care plan can no longer be made; factors present in family carers and professionals can influence decision-making and the ACP process; ACPs are affected by preferences for life sustaining treatments; ACP in dementia may differ from other illness groups; and there is a need for education relating to ACP.

Conclusion: The current evidence base for ACP in dementia is limited. Since UK government policy recommends that all people should engage in ACP, more evidence is needed to understand the feasibility and acceptability of advanced care plans for people with dementia.

Rapid transcranial magnetic stimulation (rTMS) applied to the left dorsal lateral frontal cortex has been shown to produce antidepressant effects. Older depressed patients, however, in one study showed a lower response rate than younger patients. The current study examined treatment response in 20 depressed, treatment-refractory patients (mean age 60.7 ± 9.8 years) given five sessions of rTMS at 20 Hz for 2 seconds over 20 trains at 80% of motor threshold or identical placebo stimulation, after patients had been withdrawn from their antidepressants. There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days' follow-up. There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders (p=.03). These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS.

Background: Cognitive training (CT) may be effective as a therapeutic strategy to prevent cognitive decline in older adults. This review evaluates CT as a preventive tool at various stages of a prevention hierarchy with specific reference to healthy older adults, “at risk” and clinical populations. It also considers the underlying mechanism of CT, namely that which suggests that CT acts via promoting neuroplasticity.

Methods: Evidence for CT in healthy, “at risk” and clinical populations has been systematically reviewed elsewhere. This review re-examines several studies in each group to clarify the potential of CT as a preventive technique, with a key focus on the secondary level of prevention.

Results: Studies in healthy older adults and those with mild cognitive impairment are largely positive and suggest that CT has the potential to improve cognition. However, findings in relation to Alzheimer's disease are mixed. Limitations of existing research include diverse methodologies and CT programs, small samples, insufficient focus on functional outcomes, sustainability and generalization of effects and the need for imaging data to delineate mechanisms of change. Additionally, there is limited data on those with late-life depression, despite this being an independent risk factor for dementia.

Conclusions: CT offers promise as a preventive therapeutic technique in healthy older adults and particularly as a secondary prevention method for “at risk” groups. Future investigations need to focus on methodological constraints and delineating possible neuroplastic mechanisms of action. Nonetheless, CT programs may represent a viable, non-pharmacological early intervention strategy, as they are easily-implemented, engaging and promote social interaction in group settings.

Interpretation of cognitive test performance among individuals from a given population requires an understanding of cognitive norms in that population. Little is known about normative test performance among elderly illiterate non-English-speaking individuals. An age-stratified random sample of men and women, aged 55 years and older, was drawn from a community-based population in the rural area of Ballabgarh in northern India. These Hindi-speaking individuals had little or no education and were largely illiterate. A battery of neuropsychological tests, specially adapted from the CERAD neuropsychological battery, which was adminstered to this sample, is described. Subjects also underwent a protocol diagnostic examination for dementia. Norms for test performance of 374 nondemented subjects on these tests are reported across the sample and also by age, gender, and literacy.

The Canadian Study of Health and Aging (CHSA) provided an opportunity to examine the positive aspects of aging. CHSA-2 included the 18-item Ryff multidimensional measure of well-being, which taps six core theoretical dimensions of positive psychological functioning. The measure was administered to 4,960 seniors without severe cognitive impairment or dementia at CSHA-2. Intercorrelations across scales were generally low. At the same time, the internal consistency reliability of each of the 6 subscales was not found to be high. Confirmatory factor analyses provide support for a 6-factor model, although some items demonstrate poor factor loadings. The well-being measures in CSHA-2 provide an opportunity to examine broad, descriptive patterns of well-being in Canadian seniors.

Background: While dementia is more common in older people and suicide rates in many countries are higher among the elderly, there is some doubt about the association between these two phenomena.

Methods: A search of the major relevant databases was carried out to examine the evidence for this possible association.

Results: The association between dementia and suicide and also non-fatal self-harm did not appear strong but many studies have significant methodological limitations and there are few studies of suicide or self-harm in vascular, frontotemporal, Lewy body and HIV dementia where such behavior might be expected to be more common. Rates of self-harm may be increased in mild dementia and are higher before than after predictive testing for Huntington's disease. Overall, the risk of suicide in dementia appears to be the same or less than that of the age-matched general population but is increased soon after diagnosis, in patients diagnosed with dementia during hospitalization and in Huntington's disease. Putative risk factors for suicide in dementia include depression, hopelessness, mild cognitive impairment, preserved insight, younger age and failure to respond to anti-dementia drugs. Large, good quality prospective studies are needed to confirm these findings.

Conclusions: Further research should be undertaken to examine how rates of suicide and self-harm change during the course of the illness and vary according to the specific sub-type of dementia.

Background: The purpose of this study was to examine if Type 2 diabetes mellitus is a risk factor for dementia in very old age, specifically for Alzheimer's disease (AD) and vascular dementia (VaD). Methods: We evaluated the risk of dementia in relation to Type 2 diabetes using a population-based sample of 702 individuals aged 80 years and older (mean age 83 years). A total of 187 persons received a dementia diagnosis. Thirty-one individuals had a diabetes diagnosis prior to onset of the dementia. Results: Cox proportional hazard analyses, adjusted for age, gender, education, smoking habits, and circulatory diseases, indicated an elevated risk to develop VaD (relative risk = 2.54, 95% confidence interval 1.35–4.78) in individuals with diabetes mellitus. No association was found between diabetes and AD. Conclusion: Type 2 diabetes is selectively related to the different subtypes of dementia. There is no increased risk of AD but more than a twofold risk of VaD in persons with diabetes.

Background: In the U.K. about 141,460 people with dementia (PWD) live alone. They are at risk of social isolation and inadequate social and medical supervision. The aims of this study were to identify the needs of PWD living alone and to compare the needs of PWD living alone versus those living with others. It was predicted that PWD living alone would have significantly more unmet needs than those living with others.

Methods: 152 PWD were interviewed about their cognitive status and quality of life (QoL); and 128 informal carers were interviewed about the PWD's QoL, social networks, behavioral and psychological symptoms (BPSD), functional status, and services used. For 24 PWD no carer was available. Carers were also interviewed about their own symptoms of depression, anxiety, burden, and satisfaction. Researchers rated PWD's needs. One-third of the PWD (50) were living alone.

Results: PWD living alone had significantly more unmet needs (M = 3.9, s.d. 3.1) than those living with others (M = 2.0, s.d. 2.0) (U = 1578, p < 0.01) particularly in the areas of looking after home (χ2 = 17.23, p < 0.001), food (χ2 = 13.91, p < 0.002), self-care (χ2 = 10.23, p < 0.002) and accidental self-harm (χ2 = 16.51, p < 0.001). The most frequent unmet needs were daytime activities (27, 54.0%), company (26, 52.0%), psychological distress (22, 44.0%), eyesight/hearing (16, 32.0%), and accidental self-harm (16, 32.0%).

Conclusion: PWD living alone are a vulnerable group who are at increased risk for unmet social, environmental, psychological and medical needs. This study illustrates the need to identify these individuals and to make provisions among social service agencies to monitor their well-being regularly and provide a higher level of support when needs are identified.

Many people with dementia reside in care facilities. Little is known about how key parameters impact upon their quality of life (QOL). All 209 people with dementia in six facilities received a standardized assessment (Neuropsychiatric Inventory [NPI], Barthel Scale, psychotropic drugs). One hundred twelve residents were assessed using Dementia Care Mapping, an observational method for QOL indices. Lower performance on activities of daily living (reduced well-being [WB] r = +0.39, p < .0001; social withdrawal [SW] r = +0.42, p < .0001; engagement in activities [EA] r = +0.31, p = .001) and taking psychotropics (WB 2.5 vs. 3.2, t = .2.3, p = .02; SW 11.4% vs. 2.7%, t = 3.0, p = .004; EA 56.5% vs. 71.9%; t = 3.5, p = .001) were associated with reduced QOL, but symptoms from the NPI were not. More focused prescribing of psychotropics and better staff training are essential.

Normative data were collected in a study population of 150 randomly selected elderly subjects. Using the SIDAM (Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, multi-infarct dementia, and dementias of other etiology according to DSM-III-R and ICD-10), both the dimensional and the categorical aspects of dementia and “mild cognitive impairment” are considered. With the SIDAM score (SISCO) [range 0 (minimum)-55 (maximum, no cognitive impairment)] and the SIDAM Mini-Mental State Examination (MMSE) (range 0–30), appropriate cutoffs for the category of DSM-III-R and ICD-10 dementia and “mild cognitive impairment” were defined. MMSE scores of 0–22 were found to be indicative of DSM-III-R and ICD-10 dementia. For “mild cognitive impairment,” MMSE scores ranged from 23–27 according to a DSM-III-R definition (ICD-10: 23–28). An MMSE score of 22 or less was found to differentiate between DSM-III-R/ICD-10 dementia and “mild cognitive impairment,” with a specificity of 92% (ICD-10: 95.6) and a sensitivity of 96% (ICD-10: 96%). With the SIDAM-based DSM-III-R/ICD-10 diagnoses of dementia as the criterion, the SISCO was 97.3% specific (ICD-10: 99%) and 94% sensitive (ICD-10: 94%) in detecting dementia. A SISCO of 0–33 was highly indicative of DSM-III-R and ICD-10 dementia. For “mild cognitive impairment,” a SISCO between 34–47 (ICD-10: 34–51) was found. The SISCO covers a broader range of cognitive functions that the MMSE and is more useful in detecting even very mild cognitive decline. Furthermore, the newly defined category of “mild cognitive impairment” could be validated successfully by means of GDS Stages 2–3 and CDR Stage 0.5. These findings confirm the value of the SIDAM as a short diagnostic instrument for measurement and diagnosis of dementia and “mild cognitive impairment.”

Direct observations of 24 highly agitated, cognitively impaired nursing home residents were performed during each hour of the 24-hour day for 2–3 months. Results showed that agitated behaviors (in particular, strange noises, requests for attention, repetitious mannerisms, picking at things, strange movements, and pacing) were manifested at very high frequencies. The data also showed that daytime agitation was positively related to nighttime agitation. Patterns of agitation were specific to each resident, an important finding for future research and intervention.