Solitary living in Alzheimer's disease over 3 years: association between cognitive and functional impairment and community-based services.

Introduction: Many individuals with Alzheimer’s disease (AD) live alone, and this figure is expected to increase. This study aimed to describe the cognitive and functional abilities of solitary-living AD patients, and the potential predictors of their usage of community-based services. Methods: This 3-year, prospective, multicenter study included 1,021 participants with mild-to-moderate AD (Mini-Mental State Examination score, 10–26) treated with cholinesterase inhibitors (ChEI) in a routine clinical setting. At the baseline and every 6 months, patients were assessed using cognitive, instrumental and basic activities of daily living (ADL) scales, and service utilization was recorded. Logistic regression models were used to predict the usage of community-based services. Results: At the start of ChEI therapy (time of AD diagnosis), 355 individuals (35%) were living alone. They were mainly female, older, had more impaired basic ADL capacity, and a larger number of concomitant medications compared with those living with family. Regarding the solitary-living patients, lower instrumental ADL (IADL) ability and more medications were independent predictors of usage of home-help services, whereas more impaired IADL at baseline and faster IADL deterioration were predictors of nursing-home admission. For those living with family, older age, lower basic ADL, and a greater number of medications predicted home-help services, whereas a larger amount of home help predicted nursing-home placement. In addition, female sex was a risk factor for both the utilization of home-help services and nursing-home placement. Cognitive ability was not significantly associated with usage of community-based services. Conclusions: A large number of AD patients, predominantly females, live alone with severe cognitive and functional impairment. The amount of home-help services used did not reflect cognitive severity, suggesting that home help did not meet the needs related to cognitive deterioration. Increased knowledge of how community-based services can better accommodate the care needs of solitary-living individuals with AD is essential

Living Alone in Alzheimer’s Disease—The Influence of Functional Impairment.

Background: A large number of individuals with Alzheimer’s disease (AD) live alone and receive little or no help from family members, which implies an additional pressure on the increasing societal costs of dementia care. Their adult children, if any, might have very limited ability to assist by providing informal help because of social structural changes, such as full-time work for most women and sometimes a place of residence located far away from the parents’ home. About half of the informal help received has been reported to consist of surveillance, diversion from repetitive or dangerous activities, and management of behavioral disturbances. Lack of help in monitoring these expressions of AD might lead to safety issues for individuals who live alone. Moreover, difficulties in detecting increasing impairments in their cognitive and functional abilities could affect negatively the opportunities of solitary-living individuals to receive necessary formal help. Living alone with dementia is also a strong factor for nursing home placement. This study aimed to describe the cognitive and functional abilities of solitary-living AD patients, as well as the potential predictors of usage of community-based home help services (HHS). Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, open, nonrandomized, multicenter study that was undertaken the investigation of the long-term effectiveness of cholinesterase inhibitor (ChEI) treatment from various perspectives, such as cognition, activities of daily living (ADL), and usage of community-based services. Among the 1,258 outpatients with a clinical diagnosis of probable or possible AD in the SATS, 1,021 had mild-to-moderate AD (Mini-Mental State Examination (MMSE) score, 10–26) at the start of ChEI therapy (baseline). Three hundred fifty-five (35%) of these individuals were living alone at the baseline, with or without HHS, and were included in the current study. Patients were assessed regarding cognitive ability (MMSE), functional capacity (Instrumental Activities of Daily Living (IADL) scale and Physical Self-Maintenance Scale (PSMS)), and the amount of HHS (hours/week), at baseline and every 6 months for a total period of 3 years. Binary logistic regression was used to determine the individuals’ characteristics that affected the use of HHS at baseline. The following potential predictors were investigated: gender, APOE 4 carrier status, years of education, illness duration, age, number of medications, and cognitive and functional abilities at baseline. Results: At the start of ChEI therapy, 267 (75%) of the solitary-living patients were in the mild stage of AD (MMSE score, 20–26). HHS was used by 85 (32%) of the mild and 48 (55%) of the moderate (MMSE, 10–19) AD patients (P < 0.001). The mean hours of HHS used per week was 5.7 (95% confidence interval (CI), 5.0–6.5); no difference in this parameter was detected among the disease stages. The IADL capacity was already markedly impaired at baseline: 50–65% of the individuals were dependent on assistance to perform these activities (IADL score, 2–5). Regarding basic ADL, most patients were able to manage themselves independently, with the exception of physical ambulation (almost 60% of individuals needed some assistance; PSMS score, 2–5). A significant difference in mean IADL score at the start of ChEI treatment was observed between the mild and moderate AD patients: 14.6 points (95% CI, 13.9–15.2) vs 19.2 points (95% CI, 18.1–20.3; P < 0.001). The corresponding PSMS scores were 7.5 points (95% CI, 7.2–7.7) vs 8.9 points (95% CI, 8.2–9.6; P < 0.001). No difference in age or number of medications at baseline was found among the disease stages. In a logistic regression model, the variables IADL score (OR, 1.27; 95% CI, 1.17–1.38; P < 0.001) and number of medications at baseline (OR, 1.19; 95% CI, 1.07–1.33; P = 0.002) correctly classified 80.2% of the patients with AD regarding whether they used HHS at the start of ChEI therapy. After 3 years of ChEI treatment, 89 AD patients (25%) were still living alone in their own home. Of those, 65 individuals used a mean of 9.5 hours (95% CI, 7.8–11.3) of HHS per week. The cognitive ability of the solitary-living patients varied appreciably, but 80–90% could not carry out IADL tasks independently. In addition, more than 50% of the individuals needed assistance in performing the basic ADL items of grooming and physical ambulation. Conclusions: A substantial number of AD patients, predominantly females, with severe cognitive and functional impairments live alone, which might lead to safety risks for these vulnerable individuals. The amount of HHS used did not reflect disease severity. Functional, but not cognitive, ability predicted the need for home help, suggesting that HHS meets the needs related to cognitive deterioration to a lesser extent. Increased knowledge about how community-based services can better accommodate the care needs of recipients with cognitive impairment is essential

Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer's disease cohort

Background: Activities of daily living (ADL) are an essential part of the diagnostic criteria for Alzheimer's disease (AD). A decline in ADL affects independent living and has a strong negative impact on caregiver burden. Functional response to cholinesterase inhibitor (ChEI) treatment and factors that might influence this response in naturalistic AD patients need investigating. The aim of this study was to identify the socio-demographic and clinical factors that affect the functional response after 6 months of ChEI therapy. Methods: This prospective, non-randomised, multicentre study in a routine clinical setting included 784 AD patients treated with donepezil, rivastigmine or galantamine. At baseline and after 6 months of treatment, patients were assessed using several rating scales, including the Instrumental Activities of Daily Living (IADL) scale, Physical Self-Maintenance Scale (PSMS) and Mini-Mental State Examination (MMSE). Demographic and clinical characteristics were investigated at baseline. The functional response and the relationships of potential predictors were analysed using general linear models. Results: After 6 months of ChEI treatment, 49% and 74% of patients showed improvement/no change in IADL and in PSMS score, respectively. The improved/unchanged patients exhibited better cognitive status at baseline; regarding improved/unchanged PSMS, patients were younger and used fewer anti-depressants. A more positive functional response to ChEI was observed in younger individuals or among those having the interaction effect of better preserved cognition and lower ADL ability. Patients with fewer concomitant medications or those using NSAIDs/acetylsalicylic acid showed a better PSMS response. Conclusions: Critical characteristics that may influence the functional response to ChEI in AD were identified. Some predictors differed from those previously shown to affect cognitive response, e. g., lower cognitive ability and older age predicted better cognitive but worse functional response

Activities of daily living - Outcome during two years in galantamine treated Alzheimer patients

122 patients with Alzheimer's disease receiving galantamine in the Swedish Alzheimer Treatment Study were studied with respect to longitudinal change in cognition (MMSE and ADAS-cog) and function (IADL, PSMS and FAST). Particularly the FAST mean change from baseline showed a linear relationship with cognitive mean change and the strength of the relationship increased over time. The IADL scale demonstrated a faster decline of function, but significantly less than expected by using the mathematical model by Green et al. A cluster analysis was performed to reveal any natural groupings of the patients based on the functional scores at baseline. The two-cluster solution was significant; patients in cluster 1 were more cognitively impaired at baseline, they were less apt to carry the APOE e4 allele and declined faster in the outcome of PSMS score compared to the other group

Various outcomes of cholinesterase inhibitor treatment influence survival of patients with Alzheimer’s disease.

Objectives: Various outcomes of cholinesterase inhibitor (ChEI) therapy have been observed in Alzheimer’s disease (AD). It is not clear whether the duration of treatment, type of ChEI, or dose affect mortality. We aimed to investigate the association between ChEI therapy and patient survival. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study to evaluate long-term treatment with ChEIs in clinical practice. This study included 1021 outpatients with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination score, 10–26) at the start of ChEI treatment (shortly after diagnosis). The date of death of participants was recorded. Results: After up to 16 years of follow-up, 841 (82%) of the patients in the SATS had died. The mean ± standard deviation time from diagnosis of AD to death was 6.0 ± 2.9 years, and differed between individuals with varying durations of ChEI treatment in the study, from 7.2 ± 2.5 years (3-year completers) to 4.9 ± 2.9 years (<1 year) (P<0.001). Patients who received a higher mean dose of ChEIs during the study had a longer lifespan than those who received a lower dose (6.4 ± 2.9 vs 5.5 ± 2.8 years; P<0.001). The median cutoff values were donepezil 6.9 mg, rivastigmine 6.0 mg, and galantamine 15.0 mg. No difference in mortality between the types of ChEIs was found after adjusting for sex, age, and disease severity. Conclusions: Longer survival can be expected for AD patients who receive and tolerate higher ChEI doses and a longer duration of treatment

Risk Factors for Nursing Home Placement in Cholinesterase Inhibitor Treated Naturalistic Alzheimer Patients.

Aims: To analyse which factors influence nursing home placement (NHP) and time until NHP in long-term cholinesterase inhibitor treated patients with Alzheimer’s disease (AD). Methods: The Swedish Alzheimer Treatment Study (SATS) is an open, on-going, non-randomized, multicentre study in a routine clinical setting. Patients with the diagnosis of AD, living at home at the time of inclusion, receive treatment with donepezil, rivastigmine or galantamine. They are assessed with MMSE, ADAS-cog, IADL and PSMS at baseline and every 6 months over the course of 3 years. The first 883 subjects that had the opportunity to complete the full study were investigated concerning NHP; 210 of these patients were admitted to nursing homes. The following risk factors for the event NHP (Chi-square and T-tests) and the time until NHP (Cox regression) were investigated: gender, APOE e4-carrier, living alone or with spouse, education level, age, illness duration, cognitive and functional level at baseline and decline in cognition and function prior to NHP. Results: Females (p=0.002), patients living alone (p<0.001), older age (p=0.002), longer illness duration (p=0.004) and lower cognitive and functional status at baseline (p<0.001) are risk factors for admission to a nursing home. The distribution of time until NHP was significantly affected by gender (p=0.048), living alone (p<0.001) and MMSE and IADL score at baseline (p<0.001). Conclusions: Female gender, patients living alone and lower cognitive or functional ability at baseline demonstrated larger risk of early NHP. Cognitive or functional decline prior to NHP did not influence time until NHP

The effect of functional capacity and concomitant medications on life expectancy in Alzheimer’s disease.

Background: An increased knowledge of predictors that might affect survival in Alzheimer’s disease (AD) patients treated with cholinesterase inhibitors (ChEIs) is important for clinicians and for the health services. Impairment in activities of daily living (ADL), somatic diseases, and psychiatric symptoms may influence mortality in AD. We aimed to study the impact of functional capacity and concomitant medications on patient life expectancy in clinical practice. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for the long-term assessment of ChEI treatment. This study included 791 deceased participants with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination score, 10–26) at the start of ChEI therapy (shortly after diagnosis). Patients were evaluated regarding cognitive and functional abilities and concomitant medications. The date of death was recorded. Survival was compared individually with that of the sex- and age-matched general population. Results: The mean ± SD time from AD diagnosis to death was 5.7 ± 2.8 years and varied among patients with different levels of instrumental ADL (IADL) impairment at baseline, from 6.6 ± 2.8 years (IADL score, 8–12) to 5.0 ± 2.5 years (IADL score, 21–31) (P < 0.001). The time from AD diagnosis to death also differed between patients receiving antihypertensive/cardiac therapy (no/yes, 6.1 ± 2.7 vs 5.3 ± 2.8 years; P < 0.001), antidiabetics (no/yes, 5.8 ± 2.8 vs 4.1 ± 2.4 years; P < 0.001), nonsteroidal anti-inflammatory drugs (NSAIDs)/acetylsalicylic acid; no/yes, 6.0 ± 2.8 vs 5.2 ± 2.6 years; P < 0.001), and antipsychotics (no/yes, 5.8 ± 2.8 vs 4.7 ± 2.5 years; P = 0.020). IADL score at baseline and antihypertensive/cardiac therapy, antidiabetics, and antipsychotics were independent predictors of survival after AD diagnosis in a general linear model, after controlling for sex, age, and cognitive ability. Basic ADL, number of medications, and specific concomitant medications (lipid-lowering agents, NSAIDs/acetylsalicylic acid, antidepressants, and anxiolytics/sedatives/hypnotics) at baseline were not significant predictors. Conclusions: IADL, but not basic ADL, was an important predictor that should be considered by clinicians and community-based services when estimating AD prognosis. Antidiabetic therapy was a strong risk factor for reduction in life expectancy

Activities of Daily Living – Outcome During Three Years in Donepezil Treated Alzheimer Patients.

Objectives: To analyse and present the outcome of longitudinal change and possible subgroups with respect to Activities of daily living (ADL) function measured by different scales (PSMS, FAST and IADL) in patients treated with donepezil for three years (n=435). Methods: The Swedish Alzheimer Treatment Study (SATS) is an open, 3-year, multicentre study in a routine clinical setting. The patients were assessed with several rating scales including ADL at baseline and every 6 months for a total period of three years. IADL scores were compared to the expected change in untreated patients based on a mathematical model by Green et al. A two-step cluster analysis was performed to reveal any natural groupings (clusters) of the patients based on the ADL scores at baseline. Results: After three years of donepezil treatment the total mean change in PSMS score was 3,2 ± 3,6 and in FAST 1,8 ± 2,1 points. The three-year change in IADL-score was 6,1 ± 5,4 points whereas the expected change using the mathematical model was 15,8 ± 5,6 points. The different ADL scales were linearly correlated with each other and with cognition measured by MMSE and ADAS-cog at all assessment points. However, the strength of the relationship increased over time with p-values < 0,000 from 18 months and onwards. The three scales showed no significant difference between gender at baseline but after three years the IADL mean decline from baseline was significantly worse among women. A cluster analysis showed two subgroups that significantly differed in age (p<0,000), duration (p<0,05) and cognition (p<0,000) at baseline. No significant difference in gender, APOE e4-carriers or mean dose of donepezil was observed. The two subgroups also deviated significantly in the long-term outcome of ADL score particularly measured by the PSMS scale (0,000<p<0,05). Conclusions: Increasing strength in the linear correlation between the three ADL scales as well as cognition was observed during the three years of the study. The IADL scale showed a decline of function less than expected compared with untreated patients in a mathematic model. Long term IADL scores deteriorated significantly more in the female gender than in the male. Cluster analysis based on ADL scores at baseline, identified two subgroups: with different mean age and cognitive ability and dissimilar rate of change in functional decline predominantly shown by the PSMS scale

Galantamine treatment in Alzheimer’s disease: response and long-term outcome in a routine clinical setting

BACKGROUND: In the absence of long-term, placebo-controlled studies of cholinesterase inhibitors in Alzheimer's disease (AD), analysis of the results of open-label trials becomes crucial. This study aimed to explore the three-year effects of galantamine treatment, as well as subgroups of response and adherence to treatment. METHODS: Two hundred and eighty patients with a clinical diagnosis of AD were included in the prospective, open-label, multicenter Swedish Alzheimer Treatment Study, and received galantamine treatment. Efficacy measures included cognitive tests, ie, the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog), functional rating (Instrumental Activities of Daily Living Scale [IADL]), and global rating. Assessments were carried out before treatment and every six months for a period of three years. K-means cluster analysis was used to identify response subgroups. RESULTS: After three years of treatment, the mean change from baseline was 2.6 points in MMSE and 5.6 points in ADAS-cog scores. Globally, half of the patients improved or remained unchanged for two years. Cluster analysis identified two response clusters. Cluster 1 included patients with low ability in ADAS-cog and IADL scores at baseline. Even though the patients in cluster 1 were older and less educated, they responded better at six months compared with patients in cluster 2. Cluster 2 included patients with better ADAS-cog and IADL scores at baseline. Patients in cluster 2 had a higher frequency of the APOE ɛ4 allele, a slower pretreatment progression rate, and remained in the study longer than those in cluster 1. Three-year completers (n = 129, 46%) received higher doses of galantamine compared with dropouts. CONCLUSION: AD patients who received long-term galantamine treatment were cognitively and globally stabilized. Subgroup response analysis identified a better short-term response in older patients with lower cognitive and functional abilities at baseline, a faster pretreatment progression rate, and a lower incidence of the APOE ɛ4 allele. The galantamine dose was higher in the population of completers