Background: Important public health and clinical issues remain unanswered concerning disease-related knowledge and caregiving experiences in dementia. The aim of this study is to describe these dimensions in Portuguese clinical settings and analyze the link between knowledge and burden, and also between knowledge and positive caregiving experiences.

Methods: We studied a non-randomized sample of 116 caregivers of outpatients with ICD10-DCR diagnosis of dementia. Comprehensive assessments included Dementia Knowledge Questionnaire (DKQ), Zarit Burden Interview (ZBI), Caregiving Activity Survey (CAS), Positive Aspects of Caregiving (PAC) and General Health Questionnaire-12 (GHQ). Portuguese translations for DKQ, ZBI and PAC scales had been developed; validity aspects were documented, as well as test-retest reliability coefficients for ZBI (ICC = 0.93) and PAC (ICC = 0.85).

Results: Most caregivers were close relatives, female and living with the patient. Although positive aspects of care were reported, burden and distress levels were moderate to high. Knowledge needs were not striking. Distress was moderately correlated to burden, but no associations were found between caregivers' knowledge and ZBI, PAC or GHQ. DKQ scores did not predict PAC nor ZBI scores. A relationship was found between ZBI, as dependent variable, and PAC, GHQ and CAS.

Conclusions: A large proportion of caregivers in this sample, albeit informed about dementia, were at risk of high burden and distress. Knowledge about dementia may not be protective of burden per se, nor did it influence positive aspects of caregiving.

Background: We evaluated the effects of cognitive training on self-rated health at 1, 2, 3, and 5 years post-baseline.

Methods: In the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) randomized controlled trial, 2,802 older adults (≥65 years) were randomly assigned to memory, reasoning, speed of processing, or no-contact control intervention groups. Complete data were available for 1,804 (64%) of the 2,802 participants at five years. A propensity score model was adjusted for attrition bias. The self-rated health question was coded using the Diehr et al. (2001) transformation (E = 95/VG = 90/G = 80/F = 30/P = 15), and analyzed with change-score regression models.

Results: The speed of processing (vs. no-contact control) group had statistically significant improvements (or protective effects) on changes in self-rated health at the 2, 3 and 5 year follow-ups. The 5-year improvement was 2.8 points (p = 0.03). No significant differences were observed in the memory or reasoning groups at any time.

Conclusion: The speed of processing intervention significantly protected self-rated health in ACTIVE, with the average benefit equivalent to half the difference between excellent vs. very good health.

Background: There is increasing interest in identifying novel cognitive paradigms to help detect preclinical dementia. Promising results have been found in clinical settings using the Semantic Interference Test (SIT), a modification of an existing episodic memory test (Fuld Object Memory Evaluation) that exploits vulnerability to semantic interference in Alzheimer's disease. It is not yet known how broadly this work will generalize to the community at large.

Methods: Participants aged ≥65 years from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) were administered the SIT at study entry. Independent of neuropsychological assessment, participants were rated on the Clinical Dementia Rating (CDR) scale, based on reported loss of cognitively driven everyday functioning. In individuals free of dementia (CDR <1), the concurrent validity of the SIT was assessed by determining its association with CDR using multiple logistic regression models, with CDR 0 (no dementia) vs. 0.5 (possible dementia) as the outcome and the SIT test variables as predictors.

Results: Poorer performance on all SIT variables but one was associated with higher CDR reflecting possible dementia (Odds Ratios 2.24–4.79). Younger age and female gender also conferred a performance advantage. Years of education and reading ability (a proxy for quality of education) evidenced a very weak association with SIT performance.

Conclusions: The SIT shows promise as a valid, novel measure to identify early preclinical dementia in a community setting. It has potential utility for assessment of persons who may be illiterate or of low education. Finally, we provide normative SIT data stratified by age which may be utilized by clinicians or researchers in future investigations.

Background: Neuropsychiatric disorders are common in cognitively impaired older persons, and associated with institutionalization and caregiver stress in Alzheimer's disease (AD). Few studies have compared the occurrence of both psychiatric disorders and neuropsychiatric symptoms in patients with AD and mild cognitive impairment (MCI) subtypes. We aimed to investigate the frequency of psychiatric disorders and neuropsychiatric symptoms in AD and MCI patients, compared to controls.

Methods: We included 245 outpatients of a memory clinic in Rome, Italy (119 AD; 68 multidomain-MCI; 58 amnestic-MCI) and 107 controls. Categorical disorders of depression and apathy were diagnosed with structured interviews. Symptoms were evaluated with the Neuropsychiatric Inventory (NPI). The odds ratios (OR) of patients having neuropsychiatric symptoms compared to controls were calculated with logistic regression, adjusted for sociodemographic and clinical variables.

Results: A large proportion of AD (49.6%) and multidomain-MCI (44.1%) patients had depression disorder. Apathy disorder was common in AD (51.3%) but less frequent in amnestic-MCI (6.9%) and multidomain-MCI (14.7%). AD patients were three times more likely to have depression disorders (OR = 3.0, CI = 1.1–7.6) or apathy (OR = 16.9, CI = 4.6–61.8) compared to amnestic-MCI, and seven times more likely to have apathy disorder than multidomain-MCI (OR = 7.5, CI = 3.0–19.2). After apathy and depression, the most prevalent neuropsychiatric symptoms in AD and MCI were anxiety, agitation, irritability, night-time behaviors, and appetite disturbances. There was an increasing prevalence of many neuropsychiatric symptoms with increasing severity of cognitive syndromes.

Conclusions: Clinicians should consider the relevance of neuropsychiatric disorders and symptoms in patients with cognitive disturbances, and incorporate a thorough psychiatric examination in the evaluation of patients.

Background: Computerized cognitive assessment tools have been developed to make precise neuropsychological assessment readily available to clinicians. Mindstreams batteries for mild impairment have been validated previously. We examined the validity of a Mindstreams battery designed specifically for evaluating those with moderate cognitive impairment.

Methods: 170 participants over the age of 60 years performed the computerized battery in addition to standard clinical evaluation. The battery consists of six technician-administered tests and one patient-administered interactive test sampling the cognitive domains of orientation (to time and place), memory, executive function, visual spatial processing, and verbal function. Staging was according to the Clinical Dementia Rating Scale (CDR) on the basis of clinical data but independent of computerized cognitive testing results, thus serving as the gold standard for evaluating the discriminant validity of the computerized measures.

Results: Seven participants received a global CDR score of 0 (not impaired), 76 were staged as CDR 0.5 (very mildly impaired), 58 as CDR 1 (mildly impaired), 26 as CDR 2 (moderately impaired), and 3 as CDR 3 (severely impaired). Mindstreams Global Score performance was significantly different across CDR groups (p < 0.001), reflecting poorer overall battery performance for those with greater impairment. This was also true for the domain summary scores, with Executive Function (d = 0.67) and Memory (d = 0.65) distinguishing best between CDR 0.5 and 1, and Orientation best differentiating among CDR 1 and 2 (d = 1.20).

Conclusions: The Mindstreams battery for moderate impairment differentiates among varying degrees of cognitive impairment in older adults, providing detailed and distinct cognitive profiles.

Background: Deposition of amyloid β in senile plaques and in cerebral blood vessels is one hallmark of the pathogenesis of Alzheimer's disease (AD). The ability of several matrix metalloproteinases (MMPs) to degrade amyloid precursor protein leading to aggregation of amyloid β, as well as the increased expression of MMPs in post mortem brain tissue of Alzheimer's patients, indicate that MMPs play an important role in the pathogenesis of AD.

Methods: We investigated levels of MMP-2,-3,-9 and -10 in plasma and cerebrospinal fluid (CSF) of AD patients (n = 14) by gelatin and casein zymography. Comparisons between AD patients and controls relative to levels of MMP-2, MMP-3, MMP-9, and MMP-10 were made with Wilcoxon rank statistics. Pearson correlations were computed as measures of association.

Results: MMP-3 in AD was significantly elevated in plasma (p = 0.006) and there was a trend towards increase in CSF (p = 0.05). MMP-2 in CSF of AD patients was significantly decreased (p = 0.02) while levels in plasma remained unchanged. MMP-9 and MMP-10 could not be detected in CSF; MMP-10 was unchanged in plasma, but MMP-9 was significantly decreased (p = 0.02).

Conclusions: These findings constitute further evidence for the important role of MMPs in the pathogenesis of AD.

Background: Investigations of mental health literacy are important because the recognition of a mental health problem is the first step in seeking appropriate mental health care. Lack of recognition is a significant barrier to accessing mental health resources. Older Chinese immigrants are at increased risk for depression; however, there is no research investigating their depression literacy, including their beliefs about treatment, etiology, and prognosis.

Methods: This study investigated depression literacy among 53 older Chinese immigrants in Canada (aged 55–87 years) and compared their literacy to Canadian-born participants of the same age who were part of a larger population-based survey. Depression literacy was assessed through interviews using a case vignette and included the following indices: rates of correct identification of depression; perceived efficacy of various people, professions and treatments; and perceptions of etiology and prognosis.

Results: In the Chinese sample, 11.3% correctly identified depression in the case vignette. In contrast, 74.0% of participants in the population-based survey correctly identified depression. Differences in the perceptions of helpful people and interventions, etiology, and prognosis were also noted between the samples. Both samples strongly endorsed physical activity as helpful in the treatment of depression.

Conclusions: In light of these results, it is clear that older Chinese immigrants would benefit from information regarding the symptoms, etiology, and treatment of depression, and that this information may begin to address the serious underutilization of mental health services among this group. Our discussion highlights practice implications and promising interventions.

Background: Developments in data collection technology enable evaluation of kinematic characteristics of the drawing process. We examined the clock drawing task in elderly patients with mild Major Depressive Disorder (MDD), assessed the relative importance of kinematic measures that differentiate the groups and analyzed associations between computerized measures, and the cognitive and depression status of the study groups.

Methods: The participants comprised 20 elderly people with mild MDD and 20 matched controls. Both groups performed a clock drawing task using a computerized system. Kinematic measures included: number of segments drawn, performance time, pressure implemented towards the drawing surface, and pen azimuth. Three representative spatial characteristics were analyzed per segments drawn on the paper: height, width and length. The clock drawing tasks were blindly scored with Freedman's method. Cognitive state was quantified using the Mini-mental State Examination (MMSE) and depression with the Geriatric Depression Scale (GDS).

Results: Freedman's method found no between-group differences. Pressure and azimuth measures and spatial measures of segments height, width and length were significantly lower in the mild MDD group, while the number of paper segments and performance time did not differ. The azimuth measure correlated with the GDS score, and pressure with the MMSE and the GDS scores. Spatial measures did not correlate with either the MMSE or GDS. Pressure, segment width and length, azimuth and segment height allowed correct classification of 81.1% of the participants.

Conclusions: A computerized system focusing on the clock drawing task might be sensitive to altered performance among elderly people with mild MDD.

Background: Late-onset Alzheimer disease (LOAD) is a clinically heterogeneous complex disease defined by progressively disabling cognitive impairment. Psychotic symptoms which affect approximately one-half of LOAD subjects have been associated with more rapid cognitive decline. However, the variety of cognitive trajectories in LOAD, and their correlates, have not been well defined. We therefore used latent class modeling to characterize trajectories of cognitive and behavioral decline in a cohort of AD subjects.

Methods: 201 Caucasian subjects with possible or probable Alzheimer's disease (AD) were evaluated for cognitive and psychotic symptoms at regular intervals for up to 13.5 years. Cognitive symptoms were evaluated serially with the Mini-mental State Examination (MMSE), and psychotic symptoms were rated using the CERAD behavioral rating scale (CBRS). Analyses undertaken were latent class mixture models of quadratic trajectories including a random intercept with initial MMSE score, age, gender, education, and APOE ϵ4 count modeled as concomitant variables. In a secondary analysis, psychosis status was also included.

Results: AD subjects showed six trajectories with significantly different courses and rates of cognitive decline. The concomitant variables included in the best latent class trajectory model were initial MMSE and age. Greater burden of psychotic symptoms increased the probability of following a trajectory of more rapid cognitive decline in all age and initial MMSE groups. APOE ϵ4 was not associated with any trajectory.

Conclusion: Trajectory modeling of longitudinal cognitive and behavioral data may provide enhanced resolution of phenotypic variation in AD.

Background: Predisposing factors alone explain only a limited proportion of the variation in fall events, especially in people with dementia. The aim of this study was to identify precipitating factors for falls among people with dementia.

Methods: We examined prospective fall registrations over a two-year period on a psychogeriatric hospital ward in the north of Sweden. Circumstances associated with each fall event were analyzed by independent reviewers, possible precipitating factors were documented, evaluated and the most likely precipitating factors were identified. In total, 223 patients with any type of diagnosed dementia were admitted to the ward and 91 fell at least once. Of these, 46 were women and 45 were men (mean age 80.3 years, range 60–94).

Results: A total of 298 falls were registered, 62% of which were sustained by men. The most likely factor or combination of factors could be ascertained in 247 falls (83%). Falls took place at all hours but almost half of the falls (44%) occurred during the nightshift (between 9pm and 7am). Acute disease or symptoms of disease and/or acute drug side-effects were, alone or in combination with other factors, judged to precipitate more than three out of four falls.

Conclusion: It is possible to identify many precipitating factors that may contribute to a fall. Falls in people with dementia should be regarded as a symptom of acute disease or as a drug side-effect until proven otherwise. Prompt detection of these relevant factors is, therefore, essential.

Background: Dementia and depression are common in advanced age, and often co-exist. There are indications of a decreased prevalence of depressive symptoms among old people in recent years, supposedly because of the manifold increase in antidepressant treatment. Whether the prevalence of depressive symptoms has decreased among people in different stages of dementia disorders has not yet been investigated.

Methods: A comparison was undertaken of two cross-sectional studies, conducted in 1982 and 2000, comprising 6864 participants living in geriatric care units in the county of Västerbotten, Sweden. Depressive symptoms were measured using the Multi-Dimensional Dementia Assessment Scale (MDDAS), and the cognitive score was measured with Gottfries’ cognitive scale. Drug data were obtained from prescription records.

Results: There was a significant decrease in depressive symptom score between 1982 and 2000 in all cognitive function groups except for the group with moderate cognitive impairment. Antidepressant drug use increased in all cognitive function groups.

Conclusion: The prevalence of depressive symptoms decreased between 1982 and 2000, in all levels of cognitive impairment except moderate cognitive impairment. This might possibly be explained by the depressive symptoms having different etiologies in different stages of a dementia disorder, which in turn might not be equally susceptible to antidepressant treatment.

Background: This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors (SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimer's disease (AD) living at home.

Methods: The study was conducted in two different outpatient neurological clinics. 338 patients with probable AD were treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinician's judgment and were observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1), three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated with SSRIs).

Results: At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change −0.8 ± 2.3 vs 0.04 ± 2.9; p = 0.02) and patients depressed and treated with SSRI (mean change −0.8 ± 2.3 vs 0.1 ± 2.5; p = 0.03).

Conclusions: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition.

Background: Cognitive decline in old age varies among individuals. The identification of groups of individuals with similar patterns of cognitive change over time may improve our ability to see whether the effect of risk factors is consistent across groups.

Methods: Whilst accounting for the missing data, growth mixture models (GMM) were fitted to data from four interview waves of a population-based longitudinal study of aging, the Cambridge City over 75 Cohort Study (CC75C). At all interviews global cognition was assessed using the Mini-mental State Examination (MMSE).

Results: Three patterns were identified: a slow decline with age from a baseline of cognitive ability (41% of sample), an accelerating decline from a baseline of cognitive impairment (54% of sample) and a steep constant decline also from a baseline of cognitive impairment (5% of sample). Lower cognitive scores in those with less education were seen at baseline for the first two groups. Only in those with good performance and steady decline was the effect of education strong, with an increased rate of decline associated with poor education. Good mobility was associated with higher initial score in the group with accelerating change but not with rate of decline.

Conclusion: Using these analytical methods it is possible to detect different patterns of cognitive change with age. In this investigation the effect of education differs with group. To understand the relationship of potential risk factors for cognitive decline, careful attention to dropout and appropriate analytical methods, in addition to long-term detailed studies of the population points, are required.

Background: Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription.

Methods: REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI).

Results: A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI ≥ 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression.

Conclusions: The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.

Background: Understanding the prevalence, incidence and cofactors of depression among long-term elderly nursing home (LTNH) residents domiciled for eight months or more may help optimize depression treatment in this vulnerable group. We quantified first year depression in American LTNH residents and the associations between depression and resident/facility characteristics.

Methods: Data were obtained from the Minimum Data Set and Online Survey Certification and Reporting for 634,060 LTNH residents admitted from 1999 to 2005 in 4,216 facilities. Depression first diagnosed at admission and at subsequent quarterly intervals through the first year of stay was examined. Logistic regressions modeled correlates of newly identified depression in each time-period.

Results: Recorded depression at admission and during the first year increased from 1999 to 2005. By 2005, 54.4% of LTNH residents had depression diagnosed over the first year; 32.8% at admission and a further 21.6% later during the first year. Antidepressant use was reported prior to depression diagnosis for 48% of those first identified depressed after admission. Men, non-Hispanic blacks, never married, and severely-cognitively impaired LTNH residents were less often identified with depression, particularly at admission. Pain and physical comorbidity were positively associated with depression identified throughout the first year. Prior institutionalization was associated with depression at admission, but not new depression after admission. Facility characteristics had weaker associations with depression.

Conclusions: High depression rates at admission and during the first year indicate a need to monitor and treat large numbers of American LTNH residents for depression. Reduced associations between demographics and depression as stays progress suggest other factors have increased roles in depression etiology.

Background: We explored phenotypic parameters of people with Huntington's disease who had been admitted to a psychiatric unit and then discharged, with a view to determining prognostic factors for discharge to higher levels of care.

Methods: A cross-sectional study was carried out on 19 patients admitted to a psychiatric unit with Huntington's disease. Data on the Unified Huntington's Disease Rating Scale (UHDRS) of behavior and function, global assessment of presence of depression and dementia as well as discharge outcomes were collated. Appropriate parametric and non-parametric statistical tests were applied.

Results: Fourteen patients were discharged to accommodation with the same level of care versus five who were discharged to a higher level of care. Having poor functioning in terms of activities of daily living predicted discharge to an increased level of care. Being depressed or having dementia did not forecast poor outcome. The total duration of admission was not related to UHDRS parameters.

Conclusions: Poor functioning on admission independently predicts the need for higher levels of care for patients who are admitted to a neuropsychiatric ward.

Background: Family care of frail elderly people has been linked to significant negative consequences for caregivers' mental health. Although outcome variables such as burden and depression have been widely analyzed in this population, guilt, an emotion frequently observed in caregivers, has not received sufficient attention in the research literature.

Methods: Face-to-face interviews were carried out with 288 dementia caregivers. Guilt was measured using the Caregiver Guilt Questionnaire (CGQ).

Results: Using principal components analysis, 22 items were retained and five factors were obtained which explained 59.25% of the variance. These factors were labeled: guilt about doing wrong by the care recipient, guilt about not rising to the occasion as caregivers, guilt about self-care, guilt about neglecting other relatives, and guilt about having negative feelings towards other people. Acceptable reliability indexes were found, and significant associations between the CGQ and its factors and the Zarit Burden Interview guilt factor were also found. Caregivers with higher scores on the CGQ also scored higher in depression, anxiety, frequency and appraisal of behavioral problems. Negative associations between the CGQ and its factors and frequency of/and satisfaction with leisure and social support were also found. Being female and caring for a parent were associated with higher scores on the CGQ.

Conclusions: Feelings of guilt are significantly related to caregiver distress. The CGQ may be a useful measure for acknowledging feelings of guilt in caregivers; moreover, it can be used as an outcome variable for psychoeducational interventions aimed at reducing caregiver distress.

Background: Plasma homocysteine has been associated with reduced brain volumes in cross-sectional studies. We aimed to investigate if homocysteine is associated with ongoing atrophy, and if so, if this is localized to gray or white matter.

Methods: In a group of 80 hypertensive subjects aged 70–90 years (from the SCOPE study) MRI images were obtained at two time points two years apart. Rates of gray and white matter and hippocampal atrophy were determined by calculating the difference in segmentation probability maps using SPM5. Plasma homocysteine, folate, B12 and creatinine were measured at study end.

Results: Homocysteine levels correlated with white matter atrophy rate (p = 0.006) hippocampal baseline volume (p = 0.011) and hippocampal atrophy rate (p = 0.004) but not global gray matter atrophy or baseline gray or white matter volumes. The correlations remained significant (p < 0.05) after controlling for subject age, blood pressure, folate levels and white matter lesion volume.

Conclusion: In older hypertensives, plasma homocysteine levels are associated with increased rates of progressive white matter and hippocampal atrophy.

Background: Hospital-treated deliberate self harm and suicide among older adults have rarely been examined at a national level.

Methods: The Irish Central Statistics Office provided suicide and undetermined death data for 1980–2006. The National Registry of Deliberate Self Harm collected data relating to deliberate self harm presentations made in 2006–2008 to all 40 Irish hospital emergency departments.

Results: Rates of female suicide among older adults (over 55 years) were relatively stable in Ireland during 1980–2006 whereas male rates increased in the 1980s and decreased in more recent decades. Respectively, the annual male and female suicide and undetermined death rate was 22.1 and 7.6 per 100,000 in 1997–2006. Male and female deliberate self harm was 3.0 and 11.0 times higher at 67.4 and 83.4 per 100,000, respectively. Deliberate self harm and suicide decreased in incidence with increasing age. Deliberate self harm generally involved drug overdose (male: 72%; female 85%) or self-cutting (male: 15%; female 9%). The most common methods of suicide were hanging (41%) and drowning (29%) for men and drowning (39%) and drug overdose (24%) for women. City and urban district populations had the highest rates of hospital-treated self harm. The highest suicide rates were in urban districts.

Conclusions: Older Irish adults have high rates of hospital-treated deliberate self harm but below average rates of suicide. Drowning was relatively common as a method of suicide. Restricting availability of specific medications may reduce both forms of suicidal behavior.

Background: We aimed to develop a standardization method to pool data recorded on different activities of daily living (ADL) scales in order to reduce variability of functional outcome data from Alzheimer's disease (AD) clinical trials and to better evaluate the effect of donepezil treatment on function in patients with AD.

Methods: Based on pre-specified criteria, six studies were selected from among all donepezil clinical trials in AD. Individual items from nine ADL scales used in these trials were mapped to a standardized functional scale comprising 12 domains (six basic, six instrumental); scores were transformed to a 0–100 scale. External validation of this scale yielded a concordance rate of 90.8%. For each domain, mean change from baseline to 24 weeks in the placebo and donepezil groups was compared for the total population and for subgroups stratified by baseline disease severity. Study settings included outpatient, assisted living, and skilled nursing facilities. Participants comprised 2183 patients (donepezil, 1261; placebo; 922) with baseline Mini-mental State Examination (MMSE) scores 5–26.

Results: Significant treatment differences favoring donepezil were observed for five items (two instrumental and three basic). Patients with moderate AD at baseline (MMSE 10–17) demonstrated the greatest treatment effect.

Conclusion: Functional data were successfully pooled using standardizing methodology. A beneficial effect of donepezil treatment on function was demonstrated using this standardized functional scale. Similar analyses from studies with other anti-dementia drugs may help to determine the generalizability of these findings and potentially encourage use of functional assessment as a clinical tool.