The association between Alzheimer's disease symptom severity and caregiver outcomes: a cross-sectional study.

OBJECTIVE: To determine the association between Alzheimer's disease (AD) symptom severity and caregiver outcomes. METHOD: This was a database analysis of the Alzheimer's Disease Caregiver Study, a cross-sectional, caregiver-reported study conducted in 2007. Data were collected nationwide via the Internet and in 8 cities: Detroit, Michigan; Knoxville, Tennessee; Los Angeles, California; Miami, Florida; Philadelphia, Pennsylvania; Phoenix, Arizona; St Louis, Missouri; and Washington, DC. Participants were unpaid adult caregivers of AD patients (N = 1,077). Symptom severity was measured using the Revised Memory and Behavioral Problem Checklist (RMBPC). Caregiver outcomes included the Caregiver Burden Scale, diagnosis of anxiety and depression, use of the emergency room, hospitalization, number of physician visits, and missed workdays in the past 6 months. Linear and logistic regression models were developed to assess effects of AD symptom severity on outcomes. Covariates included caregiver and patient characteristics and interactions of AD symptom severity with covariates based on previous analyses. RESULTS: Of the 1,077 respondents, 1,034 had valid RMBPC overall symptom severity scores. AD symptom severity was a significant (P < .01) predictor of all caregiver outcomes except physician visits. Each unit increase in RMBPC severity score corresponded with an increase of 0.328 (95% CI, 0.101-0.554) units in caregiver burden. Each unit increase in severity resulted in increases in physician visits (b = 0.343; 95% CI, 0.052-0.635) and absenteeism (b = 1.722; 95% CI, 0.694-2.749). For each unit increase in RMBPC severity score, caregivers had greater likelihood of emergency room use (odds ratio = 1.506; 95% CI, 1.230-1.845), hospitalization (OR = 1.393; 95% CI, 1.091-1.777), anxiety (OR = 1.506; 95% CI, 1.257-1.805), and depression (OR = 1.811; 95% CI, 1.505-2.179). CONCLUSIONS: AD symptom severity is significantly associated with poorer caregiver outcomes. Therefore, treatments that slow AD symptom progression may be beneficial to caregiver outcomes.

What do we know about quality of life in dementia? A review of the emerging evidence on the predictive and explanatory value of disease specific measures of health related quality of life in people with dementia.

OBJECTIVE: Given its complexity, there is growing consensus on the need to measure patient-rated broad outcomes like health-related quality of life (HRQL) as well as discrete functions like cognition and behaviour in dementia. This review brings together current data on the distribution, determinants and course of HRQL in dementia to investigate the predictive and explanatory value of measures of HRQL in people with dementia. DESIGN: A systematic review of papers in English published up to October 2007 to identify data on the use of disease-specific measures of HRQL in dementia. RESULTS: There are no clear or consistent associations between socio-demographic variables and HRQL. There is no convincing evidence that lower cognition or greater activity limitation is associated with lower HRQL. There is a strong suggestion that depression is consistently associated with decreased HRQL in dementia. However, the magnitude of the associations observed is moderate only and the proportion of variance explained is low suggesting that depression and HRQL are different constructs. We currently know almost nothing about the natural history of HRQL in dementia or what attributes or interventions promote or inhibit HRQL life for people with dementia. CONCLUSIONS: While in other illnesses there may be simple association between HRQL and an easily measurable clinical variable, in dementia this is not so. There are now instruments available with which to measure disease-specific HRQL directly in clinical trials and other studies that can yield informative data.

Comparison of cholinesterase inhibitor utilization patterns and associated health care costs in Alzheimer's disease.

BACKGROUND: Sustained treatment with a cholinesterase inhibitor (ChEI) is used in the management of the symptoms of Alzheimer's disease (AD). However, the characteristic declines in learning and memory seen in AD may erode the patient's ability to adhere to medication regimens with or without caregiver support. OBJECTIVES: To examine differences by type of ChEI in (1) monthly prevalence of use, (2) nonpersistence, (3) switching from the index drug to another ChEI, (4) number of days on therapy, (5) medication possession ratio (MPR), and (6) an estimate of the relationship of these characteristics to total annual health care expenditures. METHODS: Data were from the MarketScan Medicare Supplemental and Coordination of Benefits 2001-2003 database, which comprised 1.47 million Medicare beneficiaries during this 3-year time period. Inclusion criteria were: (1) aged 65 years or older; (2) at least 1 claim with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 331.0 for AD in any of 15 diagnosis fields on outpatient claims or any of 2 diagnosis fields on inpatient claims at any time during 18 months of observation; (3) at least 1 pharmacy claim for donepezil, galantamine, or rivastigmine preceded by a 6-month period without a ChEI claim; and (4) at least 12 months of follow-up data, for a minimum 18 months continuous enrollment. Multivariate analyses, including logistic regression and exponential conditional mean models, tested for cohort differences in ChEI utilization, controlling for demographics, region of the country, type of insurer, and the Charlson Comorbidity Index (comorbid diagnoses). Using exponential conditional mean models, we also examined the relationship between utilization characteristics and all-cause (i.e., not specific to AD) health care expenditures for a 12-month period, including inpatient and outpatient (physician) care, laboratory and radiology services, emergency room (ER) use, prescription drugs, and long-term care services (e.g., nursing home care, home health visits) paid by Medicare or private insurance, but excluding long-term care services paid by Medicaid. Expenditure was defined as allowed charge (i.e., the total payment received by the service provider including plan and patient paid amounts.) RESULTS: More than 70% of the patients who received ChEI therapy and who otherwise met the inclusion criteria were excluded from this study due to the absence of at least 1 claim with a diagnosis for AD. Of the 3,177 patients included in the study, the index ChEI was donepezil for 62.8% of the patients (n=1,994); 17.2% received galantamine (n=546) and 20.1% received rivastigmine (n=637). The total number of days of index therapy dispensed was greater for those starting on donepezil (mean [median, SD] days=226 [263, 115]) compared with rivastigmine (206 [233, 120], P<0.001), but was not significantly different compared with galantamine (216 [250, 119], P=0.085). Monthly prevalence of use was similar for the 3 drugs until month 5 when a smaller proportion of rivastigmine patients had index medication on hand (65.9%) compared with 72.1% of donepezil patients (P=0.003) and 72.7% of galantamine patients (P=0.012). At 12 months, the likelihood of receiving the index ChEI was higher for donepezil (61.1%) than for either rivastigmine (50.1%, P<0.001) or galantamine (56.4%, P=0.048) and was higher for galantamine than for rivastigmine (P=0.030). The rate of switching for donepezil patients was significantly lower (14.5%) than the switch rate for rivastigmine patients (21.5%, P<0.001) and was similar to the switch rate for galantamine patients (15.0%, P=0.781 for donepezil vs. galantamine; P=0.004 for galantamine vs. rivastigmine). Rates of nonpersistence, measured as having at least 1 gap in therapy of 30 days or more during the 1-year follow-up, were 63.5% for donepezil, 63.7% for galantamine (P=0.933 for donepezil vs. galantamine), and 68.0% for rivastigmine (P=0.042 for donepezil vs. rivastigmine). MPRs and total days supply of any ChEI did not significantly differ among the 3 drugs. Results of multivariate models showed that, controlling for index ChEI drug, each additional month of ChEI treatment was associated with a reduction of 1% in total all-cause health care costs. The mean (SD) total all-cause 1-year health care costs for patients initiated on the 3 ChEIs were not significantly different: $12,112 ($16,437) for donepezil, $12,137 ($19,154) for galantamine (P=0.978), and $12,853 ($14,543) for rivastigmine (P=0.278). CONCLUSIONS: During the first year following initiation of ChEI therapy, patients initiated on donepezil had a greater days supply of the index medication than did patients initiated on rivastigmine. At 12 months following treatment initiation, the proportion of patients in therapy was higher for donepezil than for either rivastigmine or galantamine and was higher for galantamine than for rivastigmine. Patients treated with either donepezil or galantamine were less likely to switch from the index drug to another ChEI than were patients treated with rivastigmine. All-cause 1-year health care costs for patients initiated on the 3 ChEIs were not significantly different.

Defining treatment response to donepezil in Alzheimer's disease: responder analysis of patient-level data from randomized, placebo-controlled studies.

BACKGROUND: Defining treatment success in progressive diseases, such as Alzheimer's disease (AD), can be challenging. OBJECTIVE: To explore the impact of employing different criteria to define a treatment 'responder' using analyses of patient-level data from randomized, placebo-controlled studies of donepezil in AD. METHODS: Trials were included in the analysis if they met several criteria, including the following: randomized, placebo-controlled trial of donepezil 10 mg/day in mild-to-moderate AD; cognition measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) or Mini-Mental State Examination (MMSE); and a 24-week endpoint and outcomes that included global assessments. Definitions of response were: improvements in cognition plus one other domain; improvement in cognition only; improvement or improvement/no change in global response; and improvement/stabilization/less than expected decline by < or = 2 or < or = 4 or < or = 6 points on the ADAS-cog. RESULTS: Five studies identified from the literature search met the specified criteria for inclusion. The response to donepezil measured by ADAS-cog varied from 26% to 63% and that of placebo from 14% to 47%, depending on the definition of improvement used. For definitions that included a less than expected decline on ADAS-cog, the more modest the effect defined, the less the drug versus placebo difference and the higher the percentage of patients meeting this definition. CONCLUSIONS: The definition of treatment 'response' in a progressive neurodegenerative disease can encompass a variety of outcomes, including short-term improvement, longer-term stabilization and a slowed decline in one or more clinically relevant symptoms or symptom domains. The ability to identify groups of people who respond to donepezil underscores the clinical utility of the medication and may contribute to more focused assessments of the cost effectiveness of cholinesterase inhibitors.

Health economics and the value of therapy in Alzheimer's disease.

In increasingly aging societies throughout the developed and developing world, Alzheimer's disease and related dementias are fast becoming a critical public health issue, exacting an enormous toll on individuals and healthcare systems. Over the past 10 years, five drugs have been developed and approved for the symptomatic treatment of Alzheimer's dementia, and several disease-modifying drugs are in various stages of clinical development. While symptomatic medications were consistently shown to have clinical benefit in numerous efficacy studies, the cost effectiveness of antidementia therapies and their value to healthcare systems remain unclear. The pharmacoeconomics of antidementia therapies is an evolving field, with several unanswered questions. This poses many challenges for biopharmaceutical companies developing these therapies, regulatory agencies responsible for their approval, and payers responsible for ensuring their availability to patients. The challenge partly relates to the unique nature of dementia as a disease of impaired cognition, behavior, and function. Thus, the selection of appropriate outcome measures that directly relate to healthcare utilization, quality of life, caregiver burden, and pharmacoeconomic analysis has been difficult. The development of meaningful and widely acceptable outcome measures, as well as novel clinical-study designs, is needed to better evaluate cost effectiveness and to demonstrate the value of therapeutics for Alzheimer's disease. Providing the decision-makers in healthcare systems with a body of evidence that demonstrates a positive relationship between clinical outcomes and the economic and humanistic benefits of antidementia therapeutics will improve patient access to novel drugs as they become available.

Change in framingham risk score in patients with schizophrenia: a post hoc analysis of a randomized, double-blind, 6-week trial of ziprasidone and olanzapine.

OBJECTIVE: To examine the change in Framingham risk score (FRS) arising from short-term treatment with ziprasidone or olanzapine. METHOD: Hospitalized adults with a primary DSM-IV diagnosis of schizophrenia or schizo-affective disorder were randomly assigned to 6 weeks of double-blind treatment with ziprasidone or olanzapine from November 21, 1998 to September 28, 2000. Data on fasting lipid levels were collected at screening and endpoint, and blood pressure was measured at screening and baseline and weekly until week 6 of treatment (or last visit). FRS for patients aged ≥30 years was calculated using an algorithm derived from the Framingham Heart Study. Baseline-to-endpoint least-squares mean changes in age-adjusted FRS by gender were compared using analysis of covariance (baseline adjusted). RESULTS: Men who received olanzapine demonstrated a mean increase in their total cholesterol levels (+18.5 mg/dL; N = 53) and low-density lipoprotein cholesterol levels (+13.0 mg/dL; N = 45), whereas men who received ziprasidone demonstrated a mean decrease in their total cholesterol levels (-8.5 mg/dL; N = 44) and low-density lipoprotein cholesterol levels (-7.2 mg/dL; N = 40) (p = .0006 and p = .004, respectively). Additionally, men who received olanzapine showed an increase in baseline FRS (+7.69%; N = 53), whereas men who received ziprasidone showed a decrease in baseline FRS (-11.06%; N = 42) (p = .09). In women, treatment differences in FSR numerically favored ziprasidone but were not statistically significant. Neither treatment had a significant effect on blood pressure. CONCLUSION: In short-term treatment, olanza-pine was associated with a significant worsening of lipid profile compared with ziprasidone, with a consequent increase in FRS versus ziprasidone. These findings, coupled with the significant weight gain in patients treated with olanzapine versus ziprasidone, warrant investigation in longer-term trials.

Patterns of healthcare utilization and costs for vascular dementia in a community-dwelling population.

BACKGROUND: While vascular dementia (VaD) is the second most prevalent dementia diagnosis, little is known about healthcare use and costs for VaD. PURPOSE: This study compares the healthcare use and costs of community-dwelling patients with VaD to patients with Alzheimer's disease (AD), other dementias (OD), cerebrovascular disease without dementia (CVD), and patients without dementia or cerebrovascular disease (controls). METHODS: Using diagnoses codes from medical claims and encounter records, 678 VaD, 1,722 AD, 957 OD, 2,718 CVD, and 14,023 controls were identified from patients enrolled in a 100,000-member group practice Medicare HMO during 1999-2002. Annual healthcare use and costs of the study groups were compared, using regression analysis to control for patient characteristics. RESULTS: VaD patients had the highest annual costs, dollars 14,387, followed by dollars 10,716 for OD, dollars 8,254 for CVD, and dollars 7,839 for AD, and dollars 5,494 for controls (p<0.0001 for all comparisons to VaD). Despite higher total direct costs, VaD patients had lower costs for physician visits and prescription drugs compared with all study groups except OD. In contrast, CVD patients had the highest costs for these services. Moreover, hospital admissions for VaD were nearly twice those for CVD, and hospital days for VaD nearly three times those for CVD, despite the high prevalence of cardiovascular conditions for both VaD and CVD. CONCLUSIONS: VaD patients had higher healthcare costs compared to all other patient groups. The substantially higher costs for VaD compared to CVD and the differences in use of healthcare services by VaD compared to CVD suggest that dementia, not cerebrovascular disease, is a major source of the cost differences. Lower costs for physician visits and prescription drugs for VaD suggest possible opportunities for improving ambulatory care and preventing high-cost hospitalizations.