Targeting Functional Decline in Alzheimer Disease

Alzheimer disease and related dementia lead to a high burden for patients, families, and society (1). Over the typical disease course of 5 to 10 years, the condition results in progressive functional disability, frequent transitions in care, and excess health care costs (25). Alzheimer disease has no known cure or disease-modifying treatments (6). In the context of the disease, functional decline is believed to be the result of progressive deficits in cognitive, emotional, and physical function. New models of Alzheimer disease care focus on a team-based approach in support of the family caregiver and seek to improve patients' quality of life (7, 8). These new care models emphasize coordination with community-based services, modifications to the patient's home, and movement toward dementia-prepared communities (9). Primary care practices often find these new models difficult to implement, because they require practice redesign, workforce retraining, community outreach, and leadership in local advocacy. Ten years ago, we reported the results of a randomized, controlled clinical trial testing the effectiveness of collaborative care among primary care patients with Alzheimer disease (10). The intervention resulted in clinically significant improvement in the quality of care and behavioral symptoms for patients and reduced stress for their family caregivers. Despite these improvements, the intervention did not slow the rate of patients' functional decline. During the past decade, several studies focusing on functional decline among patients with Alzheimer disease have shown the potential of home-based interventions to slow this decline (1116). The specific aim of this study was to conduct a 2-year randomized, controlled clinical trial to delay functional decline among older adults with Alzheimer disease by comparing a control group receiving best-practice primary care with an intervention group receiving best-practice primary care plus a home-based occupational therapy intervention. Methods The study was approved by the Indiana UniversityPurdue University Indianapolis Institutional Review Board. A detailed description of the study design was published previously (17). The study was a randomized, single-blind, controlled clinical trial with a parallel design and a 1:1 allocation ratio. It was conducted at Eskenazi Health, an urban public health system serving Indianapolis, Indiana. Patients were enrolled from 1 of 10 primary care practices or the 1 senior care practice affiliated with Eskenazi Health. They were eligible for participation if they were aged 45 years or older and had a diagnosis of possible or probable Alzheimer disease, as determined by physicians in a memory care practice affiliated with Eskenazi Health. Eligible patients also were required to be community dwelling; to speak English; and to have a caregiver who was willing to participate in the study, had access to a telephone, and was willing to receive home visits. Research personnel assigned to each clinical site obtained written informed consent (or assent) from eligible patients and their participating family caregivers. The CONSORT (Consolidated Standards of Reporting Trials) diagram is shown in the Figure. Figure. CONSORT diagram. CONSORT = Consolidated Standards of Reporting Trials. Randomization was conducted at the patient level, stratified by type of clinic (primary or senior care). The lead statistician (S.G.) used the statistical software SAS (SAS Institute) to generate the randomization scheme in a block of 4. Sequentially numbered, sealed envelopes containing the randomization assignment for patients from each of the 2 clinics were prepared by the study statistician. Actual randomization results were compared with the preplanned randomization schedule, and no deviation was found. Description of the Control Condition Both study groups received collaborative care for dementia facilitated through the Healthy Aging Brain Center (HABC), a memory care practice that provided comanagement with the primary care practice (18, 19). We considered this approach best-practice primary care because it encompassed the collaborative care intervention tested in our previous clinical trial (10). Based on the patient's current symptoms, as reported by the caregiver using the HABC Monitor (20), individualized recommendations were made to manage the patient's behavioral symptoms (21). Items reported by the caregiver dictated activation of specific behavioral intervention protocols by the care manager. Each of these protocols focused first on nonpharmacologic interventions. If the nonpharmacologic approach did not result in acceptable improvement, the care manager collaborated with the primary care or memory care practice physician to consider protocol-based drug therapy. Description of the Intervention The study intervention was described previously (22). Briefly, the intervention group received all of the components of best-practice primary care described earlier plus a home-based intervention designed to slow functional decline. Any study patient or caregiver, regardless of group, could receive any other concomitant care prescribed by their providers. The framework of the intervention was based on general occupational therapy principles (22) as well as interventions described in earlier published studies (1113, 23). The main goal was to support and augment the self-care functional capability of the patient, as identified by goals established in negotiation with the patient and caregiver. The occupational therapist completed an initial in-home evaluation to develop a formal care plan tailored to the needs of the patientcaregiver dyad, and he or she repeated the evaluation at the beginning of each additional cycle. Three cycles of the home-based intervention were completed over 2 years. In the first cycle, eight 90-minute sessions were delivered approximately every other week for 16 weeks. At each visit, the therapist introduced a new task based on a mutually agreed-on care plan. In the second cycle, the 8 home visits occurred every 4 weeks and therefore were completed in 32 weeks. In the third cycle, the 8 visits took place over 1 year. Between visits, any problems or new concerns on the part of the caregiver were addressed via telephone. The phone calls continued in the same progression throughout the 3 cycles, but with more weeks between contacts. Over 2 years, each dyad could receive up to 24 homes visits by 1 or more of 5 occupational therapists or 1 occupational therapy assistant; however, only an occupational therapist, not an assistant, could complete the initial assessment and care plan. Outcome Measures Outcome measures were completed in each patient's home by 2 research assistants who were blinded to the dyad's randomization status. The primary outcome measure was the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale (ADCS ADL), which assesses the traditional basic activities of daily living as well as variations in instrumental activities of daily living and several more complex and explicit self-care tasks (24). Scores vary from 0 to 75, with higher scores indicating better function. Because this scale is based on reports by the caregiver, we also completed 2 patient performance measures. The Short Physical Performance Battery (SPPB) is a standardized measure of lower-extremity physical performance that includes walking, balance, and power tasks (2527). Scores vary from 0 to 12, with higher scores indicating better function. The Short Portable Sarcopenia Measure (SPSM), conceptualized as a measure of sarcopenia that combines muscle quantity and function (28), is based on timed chair rises, lean mass, and grip strength divided by height. Scores range from 0 to 18, with higher scores indicating better function. We previously reported good correlation between these 3 scales and caregiver-reported function across a range of patients' cognitive function (29). Those findings suggested that the patients could adequately understand and follow instructions for performing the SPPB and SPSM. To help compare our outcomes with those of our previous clinical trial of collaborative care alone, we also completed the ADCS Group Neuropsychiatric Inventory at each assessment (3032). Scores on this instrument range from 0 to 144, with higher values representing worse symptoms. We also collected a broad range of process-of-care data. Statistical Analysis The study was designed for 80% power based on a 2-tailed test at a 5% significance level to test the hypothesis that patients in the intervention group would have better function than those in the control group at 24 months, with an effect size of 0.23 SD based on the ADCS ADL. Thus, the targeted sample size was 180 patients. All participants were randomly assigned according to the randomization scheme and were analyzed in the group to which they were assigned. Dementia-specific care processes were compared between the 2 groups by using 2 sample t or Wilcoxon rank-sum tests for continuous variables and Fisher exact tests for categorical variables. For each outcome measure collected at baseline and 6, 12, 18, and 24 months, a mixed-effects model was used, with time and an interaction between group and time as independent variables, whereas randomization stratum and within-patient correlation over time were adjusted for by using an unstructured covariance matrix. Main effect for group was not included in the mixed-effects models in order to enforce the equal group mean assumption at baseline given the randomized trial design (33). Two sensitivity analyses were conducted to assess the potential effect of missing data (Appendix). First, multiple imputation for patients with missing follow-up data was done for those whose data were missing for reasons other than death. We used a regression imputation approach incorporating the patients' baseline characteristics and observed outcomes with separ