Donepezil has been shown to improve aspects of cognitive functioning in persons with Alzheimer's disease (AD), but its impact on instrumental activities of daily living has received little attention. In a within-subject design, 24 community-dwelling persons with AD were treated with open-label donepezil over a 12-month period. To assess functional abilities, a brief, objective measure of instrumental activities of daily living skills was used (Texas Functional Living Scale; TFLS). Global cognitive abilities were assessed with the Mini-Mental State Examination (MMSE). Changes in TFLS and MMSE scores were much the same. Improvements on the TFLS and MMSE were seen over a 3-month period. At 12 months, both TFLS and MMSE scores declined slightly below baseline. These results support an effect of donepezil on cognitive measures and day-to-day function and also suggest that the MMSE reflects well the actual functional ability of persons with moderate AD.

This article describes the met and ummet needs of elderly residents of nursing care (NC) and residential care (RC) settings. Thirty-four residents of an RC home and 40 residents of two NC settings were assessed. Each resident and a respective staff member were interviewed using the Camberwell Assessment of Need for the Elderly (CANE) to indicate the resident's current met and unmet needs. The Clifton Assessment Procedure for the Elderly–Behaviour Rating Scale (CAPE-BRS) was completed by the staff member to indicate the participant's current level of dependency. In addition, the Mini-Mental State Examination was administered to participants and DSM-IV diagnosis was recorded. A high number of needs were found in both RC and NC settings, the level of dependency being proportional to level of need. There was a core set of needs in both samples related to difficulties with accommodation, food preparation, and self-care. Both NC and RC homes were meeting these needs; however, RC residents had a significantly greater level of unmet need for suitable daytime activities. The greatest predictor of type of setting was gender and there were significantly more females in RC. Controlling for gender, participants in NC had greater levels of dependency, particularly problems with apathy and social skills, as measured on the CAPE-BRS. It is possible that the greater level of social needs in NC residents had led to their placement in the more specialized NC settings. On the other hand, NC settings may be left caring for a group of residents that, because of their specific needs, have been difficult to place into RC. These findings have clinical implications for the future development of continuing care for the elderly. This study also highlighted that there is a substantial need for specialist services to address the unmet needs in these two types of continuing-care settings, such as interventions for social disturbances in NC and suitable daytime activities in RC. The CANE is a useful instrument to evaluate such needs in long-term-care settings.

Background: We aimed to assess why carers seek participation for their relatives in clinical trials of Alzheimer's disease (AD) medications, and to assess carer impressions of the value of trial participation. Method: A retrospective questionnaire was sent to 31 carers of participants in clinical trials for AD conducted at the Mental Health Research Institute and the National Aging Research Institute between January 1997 and December 1999. Results: Twenty-five questionnaires (81%) were returned, completed to an extent to permit analysis. Helping a relative feel better, contributing to medical science, and hoping for a cure were the main reasons for trial participation. In general, carers found the regular consultation with research staff supportive and would recommend trial participation to others. Conclusion: A greater understanding of the motivations of carers may aid the recruitment and retention of participants in clinical trials.

This study examined the utility of the TELE, a telephone assessment for dementia, in a sample of 269 individuals that was not selected on the basis of previous dementia diagnosis. Thus, the conditions of the study reflect the actual situation in which a screening instrument might be employed. Scores on TELE were compared to dementia diagnoses. Using the best cutoff score, sensitivity was .86 and specificity was .90. Longitudinal follow-up established that false positives primarily included those who subsequently developed dementia. Telephone screening for dementia has both clinical and research applications. One recommendation based on our experience is that longitudinal studies should include a telephone interview component for anyone who drops out of the study, to enable characterizing the cognitive status of dropouts.

Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BuChE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD. The two enzymes differ in substrate specificity, kinetics and activity in different brain regions. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine analogues, MF-8622) and the dual inhibitor of both AChE and BuChE, rivastigmine, indicates potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. Recent evidence suggests that both AChE and BuChE may have roles in the aetiology and progression of AD beyond regulation of synaptic ACh levels. The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options.

The association between the APOE gene and Alzheimer's disease and other forms of dementia has been widely documented, but its relevance as a genetic risk factor in specific ethnic groups other than Caucasians in the United States and Europe is limited. The aim of this work was to describe the distribution of the APOE genotype in 80 subjects of Spanish origin, over 60 years old, who were institutionalized in the Spanish Hospital of Mexico City. Thirty-eight subjects who met the DSM-IV and ICD-10 criteria for Alzheimer's disease or vascular dementia and 42 controls without dementia underwent genotyping. APOE ε allele frequencies were as follows: for affected individuals, ε2, 7.9%, ε3, 69.7%, and ε4, 22.4%; for controls, ε2, 4.8%, ε3, 91.6%, and ε4, 3.6%. The higher frequency of the ε4 allele in the affected group (χ2 = 14.5; df = 4, p = .006) confirms an association between this APOE molecular variant and dementia in elderly Spaniards.

Objectives: To investigate what kind of changes spouse caregivers of demented patients experience after the onset of dementia (a) in the general atmosphere, happiness, and relations of marriage and (b) in the sexual side of marriage. Design: Semistructured telephone interviews of spouse caregivers of demented patients. Setting: Community-living demented patients and their spouse caregivers in eastern Finland. Participants: The spouse caregivers of 42 demented patients recruited from a previous intervention study. Measures: The questionnaire covered different areas of marriage from the time before and after the onset of dementia. Results: A statistically significant decline had occured in extent of happiness (p = .012), in equal relations (p = .001), and in patients' expressions of sexual needs (p < .001) when compared the time before and after dementia. Twenty-five (60%) of the caregivers reported that the demented patient had shown at least one negative sexual behavioral change during the course of dementia. Seven male patients (24%) had shown the behavioral symptom of constantly expressing need for making love. One in 10 caregivers had experienced positive sexual behavioral changes. In one third of the patients, the expressions of tenderness towards the caregiver had increased. Dementia did not affect significantly the general atmosphere of the marriage. Out of those still in home care, at 3 years from the onset of dementia, 19 couples (46%) continued to practice intercourse, at 5 years the number was 15 couples (41%), and at 7 years it had declined to 7 couples (28%). Conclusions: Dementing illness has a major negative impact on many dimensions of marriage. However, there are also positive changes and preserved aspects of marriage. Dementia seems to have a surprisingly little impact on whether the couple continues to have intercourse when compared with the general aging population.

The correlates of dropout, efficacy, and adverse events in the tratment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (ChEI) are unclear. To investigate these issues, a 26-week prospective, randomized, open-labeled trail with donepezil or rivastigmine was undertaken. Sixty-four Korean patients with AD were recruited, and data on sociodemographic and clinical characteristics and several assessment scales were collected. Characteristics of available caregivers were also gathered. Information on adverse events and dropout was recorded. Thirty-five (55%) patients dropped out during treatment with ChEI, for reasons mainly related to financial burden of caregivers. Of the 29 patients who completed the 26-week trial, 16 (55%) were responsive to ChEI. Lower scores on the Clinical Dementia Rating and Blessed Dementia Scale at baseline were associated with the efficacy of ChEI. Of the total participants, 26 (41%) experienced adverse events, although these seemed to be mild and appeared to be associated with the psychological state of patients or coadministration of psychotropic drugs. In conclusion, ChEI seemed to be effective and well tolerated in the treatment of Korean patients with AD, but the use of this drug was limited mainly by the financial burden of caregivers.

This review provides an overview of the three most widely used cholinesterase (ChE) inhibitors: donepezil, rivastigmine, and galantamine. Differences in pharmacologic profiles will be discussed, and consideration will be given to how such differences may relate to and influence the clinical efficacy and tolerability of the various agents. In addition to providing cognitive benefits in patients with Alzheimer's disease (AD), growing clinical evidence also suggests that ChE inhibitors can produce favorable and clinically relevant effects on neuropsychiatric/behavioral disturbances and activities of daily living. Furthermore, recent data indicate that these agents may be effective at all levels of disease severity and for all rates of disease progression. The clinical utility of ChE inhibitors in a wider spectrum of dementias which share a common cholinergic deficit, such as Lewy body dementia, Parkinson's disease dementia, and vascular dementia, is currently under investigation. Beyond symptomatic relief, data suggest that ChE inhibitors may also slow the underlying disease process. As clinical and research experience with these agents continues to accumulate, the differences in their effects will become more apparent and will help physicians tailor ChE inhibition treatment to the needs of the individual patient.

Objective: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. Methods: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5–17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiaric Inventory (NPI). Results: Baseline demographics were similar between the treatment groups. Least squares mean (± SE) baseline NPI 12-item total scores were 19.55 ± 1.48 and 19.30 ± 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). Conclusions: Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.

The aim of this study was to describe the epidemiological features of agitation and aggressiveness in elderly individuals living in French nursing and retirement homes in the year 2000. Data were collected on the type, time of onset, and duration of symptoms, medical evaluation and treatment, and medical and psychiatric comorbidities of the elderly patients. The most frequently reported behavior was verbal aggressiveness and the least reported behavior was physical aggressiveness. A triggering factor initiating the symptoms of agitation or aggressiveness was reported in 61% of the cases. In 61% of the study population, there were several morbidities reported as caused by the agitated or aggressive behavior (anorexia, weight loss, dehydration). A specialist was consulted for nearly half of the agitated or aggressive patients. For 55% of the patients, a new medication regimen was started or the administration of previous medications was modified, the most frequently prescribed drugs being antipsychotics. The results of our study and others show that agitation and aggression have a substantial impact on the lives of the elderly population, as well as on the lives of their family members and caretakers.

Background: Volumetric magnetic resonance imaging (MRI) has been extensively studied in the last decade as a method to help with the clinical diagnosis of Alzheimer's disease (AD). In recent years, researchers have also started investigating if that technique would be useful to identify individuals with mild cognitive impairment (MCI), differentiating them from AD patients and from normal elderly controls. This research project was planned to assess the accuracy of volumetric MRI to differentiate those groups of individuals. Method: The investigation involved 39 patients with diagnosis of mild to moderate dementia in AD, according to the criteria of the NINCDS-ADRDA, DSM-III-R, and ICD-10; 21 subjects with complaints of cognitive decline without other psychiatric disorders (MCI); and 20 normal elderly controls. All the subjects were submitted to a standard protocol, including volumetric MRI evaluations. Results: The results indicated that all regions of interest measured (amygdala, hippocampus, and parahippocampal gyrus) were significantly different (p < .005) in AD patients compared to MCI subjects and controls. The left volumetric measures (amygdala, hippocampus, and parahippocampal gyrus) were also significantly different between the MCI subjects and controls (p < .05). The discriminant function analysis correctly classified 88.14% of the AD patients and controls, 81.67% of AD patients and MCI subjects, and 80.49% of the MCI subjects and controls. Conclusions: The results suggest that measures of medial temporal lobe regions are useful to identify mild to moderate AD patients and MCI subjects, separating them from normal elderly individuals.

The objectives of this randomized clinical trial were to investigate the impact of the discontinuation of long-term antipsychotics in residents with dementia in chronic care institutions and to identify clinical predictors of safe discontinuation. Subjects included 34 residents with dementia who were on antipsychotics for more than 6 months and whose behavior was currently stable. Subjects were randomized to either continue receiving their regular dosage of antipsychotics or to receive placebo for 6 months. Early withdrawal from the study was not statistically different between the groups (relative risk [RR] = 1.57, 95% confidence interval [CI] 0.76–3.26), and though not significantly different, subjects in the placebo group were more likely to be withdrawn from the study because of worsening behavior (RR = 1.25, 95% CI 0.33–4.76). Three subjects in the placebo group were withdrawn from the study due to worsening of extrapyramidal symptoms. The active treatment group had more behavioral problems (e.g., physical aggression towards others, p < .05) compared to the placebo group. The placebo group developed more apathy, but balancing this outcome was a relative improvement in congitive functioning. Baseline antipsychotic dose was predictive of behavioral worsening upon discontinuation of long-term antipsychotic drugs. The primary limitation of the study was the small sample size. In conclusion, a trial of discontinuation of antipsychotics should be considered in this population.

Background: Delirium is frequently observed in clinical practice, particularly in medical and surgical wards and more so among patients at risk, especially elderly with pre-existing central nervous system impairments. Objective: Despite the severe consequences of delirium, epidemiological data relating to incidence of delirium following “minor” surgery are lacking. The aim of the present study was to evaluate the incidence of delirium following cataract surgery in community-dwelling patients. Outcome: For purposes of the present study, the Confusion Rating Scale was used. Results: Of 296 patients fulfilling the inclusion criteria, 13 (4.4%) had had immediate postoperative delirium. The two variables that significantly differentiated between delirious and nondelirious patients were older age (82.1 vs. 73.06 years; p < .001) and more frequent use of benzodiazepine premedication (69% vs. 39.9%; p < .002). Conclusion: These findings suggest that the incidence of delirium following cataract surgery requires greater awareness, possibly changes in premedication, and a longer observation period in the very old.

Major advances in understanding the physiology and genetics of circadian rhythm in the past decade challenge the researcher of sleep/wake disorders in Alzheimer's disease (AD) to distinguish patient characteristics stable across the course of illness (“traits”) from characteristics that vary with stage of illness (“states”). A components-of-variance approach with a repeated measures model was used to examine the between-subjects variance over time (“trait”) vs. within-subjects (“state”) variance in 42 patients with probable AD followed, on average, over 2 years on actigraphic sleep/wake measures. Mental status scores indexed stage of illness. Actigraphic measures of sleep efficiency and circadian rhythmicity appeared predominantly “trait,” with between-individual differences accounting for over 55% of variance compared to the less than 5% of variance related to stage of cognitive impairment. We discuss how “state-trait” analyses can be helpful in identifying areas of assessment most likely to be fruitful objectives of physiologic and genetic research on sleep/wake disturbance in AD.

Objective: Falls are an everyday risk for the elderly and their etiology is multifactorial. Because there are little data focusing on falls among elderly psychiatric inpatients, we aimed to retrospectively assess the characteristics of inpatients that had sustained a fall during hospitalization. Methods: Over 4 years, all adverse-event reports of falls were reviewed. Inclusion criteria were age > 65 years and intact cognition. The control group consisted of the previous and next admission of an elderly patient to the same ward. Anti-cholinergic score was calculated for each patient. Results: Of 414 admissions of elderly patients, 34 (8.2%) patients had had a fall. The control group (n = 68) did not differ in mean age, distribution of diagnoses, or use of benzodiazepines, antidepressants, or antipsychotics. Two variables were significantly associated with falls: female gender (68% vs. 39%, p < .05) and anticholinergic burden score (ABS) (mean: 3.7 vs. 2.1, p < .05). Conclusions: Our results support reported findings of higher rates of falls among elderly women and suggest that ABS may be a risk factor for falls.

Dementia with Lewy bodies (DLB) is the second most common neuropathologically diagnosed cause of degenerating dementia after Alzheimer's disease. We report the first autopsy-confirmed case in sub-Saharan Africa in a Nigerian patient. The case presented highlights the varied clinical presentation of DLB, and is intended to raise awareness about another possible cause of dementia in Nigerian subjects.

In this exploratory study, we compared the performance of 10 African American and 26 European American persons with early-to mid-stage Alzheimer's disease (AD) to 20 nondemented elderly (NE), using a shortened version of the Test of Problem Solving (TOPS). The TOPS measures verbal reasoning to solve everyday problems in five areas: explaining inferences, determining causes, answering negative why questions, determining solutions, and avoiding problems. Six linguistic measures were also examined: total utterances, abandoned utterances, length of utterances, maze words, questions, and total words. NE performed better than AD subjects on all but one measure of verbal reasoning ability. AD subjects also showed a trend to use more total utterances and abandoned utterances than NE. For the AD group, no ethnic differences were found for verbal reasoning or linguistic measures. The findings from this preliminary investigation suggest that, compared to European Americans, African American persons with AD demonstrate similar everyday problem solving and linguistic skills. Thus, assessments such as TOPS that examine everyday problem solving may be a useful nonbiased evaluation tool for persons with AD in these two ethnic groups.