Agitation in patients with dementia: a systematic review of epidemiology and association with severity and course.

OBJECTIVES: More than 90% of individuals with Alzheimer's disease (AD) experience behavioral and neuropsychiatric symptoms (NPS), such as agitation. However, little is known regarding the specific burden of agitation for Alzheimer's patients. DESIGN: A global systematic literature review was conducted in MEDLINE and Embase for studies of clinical, humanistic, and economic burden of agitation in AD/dementia published from 2006-2016. References of identified papers and related literature reviews were examined. Studies meeting predetermined inclusion criteria for burden of agitation/NPS were summarized. RESULTS: Eighty papers met the inclusion criteria for burden of agitation in dementia. Wide ranges of agitation prevalence were reported, but few papers provided information on incidence. The association of agitation with AD severity was presented in multiple studies; a few suggested positive association of agitation with mortality. CONCLUSIONS: High prevalence of agitation is consistent with earlier reports, but several gaps in understanding of agitation in AD need further exploration.

The Symptoms Targeted for Monitoring in a Web-Based Tracking Tool by Caregivers of People With Dementia and Agitation: Cross-Sectional Study.

BACKGROUND: In people with dementia, neuropsychiatric symptoms (NPSs), especially agitation, are associated with worse quality of life and caregiver burden. As NPSs may vary with illness severity, knowledge of how people with dementia and their caregivers describe and rate the importance of agitation symptoms can improve the understanding of the clinical meaningfulness of the manifestations of agitation. The internet provides new opportunities to better understand patient experiences, as patients and caregivers increasingly look to Web-based platforms as a means of managing symptoms. OBJECTIVE: The aim of this study was to examine Web-based reports from a dementia symptom website to better understand the symptoms of agitation and explore how they are being targeted for monitoring by caregivers of people with dementia. METHODS: The Dementia Guide website hosts a Web-based database used by caregivers (97%) and people with dementia (3%). From its 61 dementia symptoms, users can select relevant symptoms that they deem important to monitor or track the effects of treatment. We employed a staging algorithm to determine if individuals had mild cognitive impairment (MCI) or mild, moderate, or severe dementia. Agitation was defined using terms consistent with the International Psychogeriatrics Association's provisional consensus definition. We compared the proportion of people with NPSs and agitation across stages of dementia severity and studied how many agitation-defining descriptors were selected, and how often they occurred, by stage. RESULTS: As of March 2017, 4121 people had used the tracking tool, of whom 2577 provided sufficient data to allow disease severity staging. NPSs were tracked by 2127/2577 (82.54%) and agitation by 1898/2577 (73.65%). The proportion in whom agitation was tracked increased with increasing cognitive impairment: 68.5% (491/717) in people with MCI, and 72.50% (754/1040), 73.3% (378/516), and 90.5% (275/304) in mild, moderate, and severe dementia, respectively (χ23=54.9; P<.001). The number of NPS and agitation descriptors selected also increased with severity (median number of NPSs=1, 2, 2, and 3 for MCI, mild, moderate, and severe dementia, respectively, Kruskal-Wallis H Test H3=250.47; P<.001; median number of agitation descriptors=1, 2, 3, and 4, H3=146.11; P<.001). CONCLUSIONS: NPSs and agitation are common targets for tracking over the course of dementia and appear more frequently with increasing disease severity. These common and distressing symptoms represent clinically meaningful targets in treating people with dementia.

Radiographic Imaging in Autosomal Dominant Polycystic Kidney Disease: A Claims Analysis.

BACKGROUND: Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly variable, with some patients progressing rapidly to end-stage renal disease (ESRD). Abdominal imaging is an important modality for verifying diagnosis in patients at risk for rapidly progressing ADPKD, targeting them for early treatment that could slow onset of ESRD. Published literature is limited on the real-world abdominal imaging utilization patterns in ADPKD. METHODS: A retrospective healthcare administrative claims analysis examining abdominal imaging scans occurring from January 1, 2014, through June 30, 2017, was conducted using the IBM MarketScan® commercial and Medicare supplemental databases. Patients in the United States who were at least 18 years old and had at least 1 inpatient claim or 2 outpatient claims (with different dates of service) with an ADPKD diagnosis code, as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM codes 753.12 [polycystic kidney, unspecified type] and 753.13 [polycystic kidney, autosomal dominant] and/or Tenth Revision (ICD-10-CM codes Q61.2 [polycystic kidney, adult type] and Q61.3 [polycystic kidney, unspecified]) were included. RESULTS: Of the 4637 patients with ADPKD (mean age, 51.2 years [SD = 15.52]), 59% had ≥1 abdominal imaging scan. Of these patients, 46% had ≥1 computed tomography (CT) scan, 25% had ≥1 ultrasound, 10% had ≥1 magnetic resonance imaging scan. Among the 1754 patients (38%) with chronic kidney disease (CKD) stage information, CT imaging was more frequent in later stages (31% stage 1 versus 68% stage 5). The proportion of patients undergoing at least 1 CT or MRI scan increased with disease severity (37% in stage 1, 42% in stage 2, 48% in stage 3, 56% in stage 4, and 71% in stage 5). CONCLUSION: Results of this analysis support the need for further investigation into abdominal imaging utilization in managing patients with ADPKD. Future research could clarify barriers and increase access to imaging, which has the potential to inform risk stratification, help patients delay dialysis or transplantation associated with ESRD, and help health systems avoid the costs associated with ESRD.

Disconnect in Assessments of Autosomal Dominant Polycystic Kidney Disease Burden Between Patients and Physicians: A Survey Study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a rare inherited kidney disorder with considerable symptom burden and negative effects even in early-stage disease. Patients' reporting of ADPKD symptom burden may differ from physicians' impressions. In this quantitative, cross-section survey study, we evaluated patient and physician assessments of symptom burden at early- and late-stage ADPKD. METHODS: In the United States, 300 patients with ADPKD and 155 physicians treating patients with ADPKD completed online surveys administered by Kantar. Disease stage was categorized as early (chronic kidney disease [CKD] stages 1-3) or late (stages 4-5). Patients completed the Work Productivity and Activity Impairment Questionnaire and reported current disease symptoms. Patients and physicians assessed impacts of ADPKD on daily life and burden of specific symptoms. Statistical analyses compared patient versus physician responses stratified by early- versus late-stage ADPKD. RESULTS: We found that impairment in work productivity was statistically greater in late- versus early-stage CKD. Compared with physicians' impressions, patients were more likely at early stages and less likely at later stages to report a moderate/strong impact of ADPKD on daily life. Among patients, 74% with early- and 88% with late-stage disease reported that ADPKD caused them to modify their daily lives. In early-stage disease, patients reported a statistically greater burden from feeling exhausted and less burden from dull kidney pain, cardiovascular problems, high blood pressure, and liver cysts than physicians assumed. At later stages, patients reported feeling exhausted and skeletal/joint pain as more burdensome, and frequent urination, high blood pressure, liver cysts, and hematuria as less burdensome, compared with physicians' impressions. CONCLUSION: The results of this survey study demonstrate a disconnect between patients' experiences and physicians' awareness of the burden of ADPKD and highlight the need for more patient/physician discussion of symptoms and disease management.

Family and Caregiver Spillover Effects in Cost-Utility Analyses of Alzheimer's Disease Interventions.

BACKGROUND AND OBJECTIVE: Alzheimer's disease or dementia can impose a significant burden on family and other informal caregivers. This study investigated how the inclusion of family/informal caregiver spillover effects in a cost-utility analysis may influence the reported value of Alzheimer's disease/dementia interventions. METHODS: We used PubMed to identify Alzheimer's disease or dementia cost-utility analyses published from 1 January, 2000 to 31 March, 2018. We reviewed and abstracted information from each study using a two-reader consensus process. We investigated the frequency and methods in which family/caregiver spillover costs and health effects were incorporated into cost-utility analyses, and examined how their inclusion may influence the reported incremental cost-effectiveness ratios. RESULTS: Of 63 Alzheimer's disease/dementia cost-utility analyses meeting inclusion criteria, 44 (70%) considered at least some family/caregiver spillover costs or health effects. Thirty-two studies incorporated spillover costs only, two incorporated spillover health effects only, and ten incorporated both. The most common approach for accounting for spillover was adding informal caregiving time costs to patient costs (n = 36) and adding informal caregiver quality-adjusted life-years to patient values (n = 7). In a subset of 33 incremental cost-effectiveness ratio pairs from 19 studies, incorporating spillover outcomes made incremental cost-effectiveness ratios more favorable (n = 15; 45%) or kept the intervention cost saving (n = 13; 39%) in most cases. In fewer cases, including spillover increased incremental cost-effectiveness ratios (n = 2; 6%), kept the intervention dominated [more costs/less quality-adjusted life-years] (n = 2; 6%), or changed incremental cost-effectiveness ratio from dominated to less cost/less quality-adjusted life-years (n = 1; 3%). In 11 cases (33%), adding spillover effects into analyses resulted in a lower incremental cost-effectiveness ratio that crossed a common cost-effectiveness threshold, which could have downstream implications for programs or policies that are adopted based on cost-effectiveness analysis results. DISCUSSION: Most Alzheimer's disease/dementia cost-utility analyses incorporated spillover costs, often as caregiver time costs, but considered spillover health impacts less often. In about 85% of the analyses, including Alzheimer's disease/dementia spillover cost or health effects decreased incremental cost-effectiveness ratios or kept the intervention cost saving. The broader value of an Alzheimer's disease/dementia intervention to society may in some cases be underestimated without considering these spillover effects on family and informal caregivers.

Institutionalization risk and costs associated with agitation in Alzheimer's disease.

INTRODUCTION: Agitation in individuals with Alzheimer's disease (AD) may predict institutionalization. This study assessed the incremental risk and costs associated with agitation in individuals with AD. METHODS: A retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (June 2005-February 2018) was conducted. Incremental risk of institutionalization associated with agitation was estimated and used with the number of institutionalized individuals with AD and agitation and costs of living by residential setting in the United States (literature-based), to estimate incremental institutionalization costs. RESULTS: The analysis included 11,348 individuals with AD: 6603 (58.2%) with and 4745 (41.8%) without agitation. Compared with individuals without agitation, those with agitation were 20% more likely to be institutionalized (odds ratio = 1.20; 95% CI = 1.08-1.33). Total incremental cost of institutionalization associated with agitation was $4.3 billion ($50,588/individual). DISCUSSION: Agitation is associated with a higher risk of institutionalization among patients with AD, which translates into a substantial economic burden.