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# Costs of Early Stage Alzheimer’s Disease in the United States: Cross-Sectional Analysis of a Prospective Cohort Study (GERAS-US)1

### Background:

Costs associated with early stages of Alzheimer’s disease (AD; mild cognitive impairment [MCI] and mild dementia [MILD]) are understudied.

### Objective:

To compare costs associated with MCI and MILD due to AD in the United States.

### Methods:

Data included baseline patient/study partner medical history, healthcare resource utilization, and outcome assessments as part of a prospective cohort study. Direct, indirect, and total societal costs were derived by applying standardized unit costs to resources for the 1-month pre-baseline period (USD2017). Costs/month for MCI and MILD cohorts were compared using analysis of variance models. To strengthen the confidence of diagnosis, amyloid-β (Aβ) tests were included and analyses were replicated stratifying within each cohort by amyloid status [+ /−].

### Results:

Patients (N = 1327) with MILD versus MCI had higher total societal costs/month ($4243 versus$2816; p < 0.001). These costs were not significantly different within each severity cohort by amyloid status. The largest fraction of overall costs were informal caregiver costs (45.1%) for the MILD cohort, whereas direct medical patient costs were the largest for the MCI cohort (39.0%). Correspondingly, caregiver time spent on basic activities of daily living (ADLs), instrumental ADLs, and supervision time was twice as high for MILD versus MCI (all p < 0.001).

### Conclusion:

Early AD poses a financial burden, and despite higher functioning among those with MCI, caregivers were significantly impacted. The major cost driver was the patient’s clinical cognitive-functional status and not amyloid status. Differences were primarily due to rising need for caregiver support.

## INTRODUCTION

Alzheimer’s disease (AD), a chronic, degenerative brain disorder, is ranked as one of the costliest conditions in the United States (US) [1, 2]. The disease burden, which affects an estimated 5.4 million Americans, impacts both patients and caregivers in terms of increased risk of morbidity and mortality and substantial costs from direct healthcare use and indirect costs such as loss of potential earnings and caregiving stress [1, 3–7].

Several studies have examined cost in patients with early signs of dementia, yet many of these studies did not confirm a diagnosis of AD [8–17]. Increasing severity of AD dementia has been found to be associated with increased costs [3, 18], yet the literature lacks estimates for the cost of illness across the full disease continuum. GERAS I, an observational study conducted in multiple European countries, found that at baseline, estimated mean monthly total societal costs were higher with greater severity when comparing patients with mild, moderate, and moderately severe or severe AD dementia [3]. At the follow-up 6-, 12-, and 18-month visits, estimated mean total societal costs generally increased from baseline [19]. For the overall 18-month period, caregiver time represented the largest resource use component, accounting for 54% to 65% of total resources depending on country [19]. Economic and treatment pattern findings from GERAS I may not reflect US healthcare patterns. Additionally, the GERAS I study did not include amyloid testing, which detects abnormal levels of amyloid-β (Aβ) neuritic plaques in the brain and is more consistent with AD diagnosis [20–22].

The primary aim of this manuscript is to describe the cross-sectional total societal costs for patients and study partners, including direct medical and nonmedical costs for healthcare resource use and indirect costs for caregiving by severity (MCI versus MILD) and by amyloid status within each severity cohort (MCI: [+] versus [−]; MILD: [+] versus [−]). This analysis uses the baseline economic data from the GERAS-US cohort study mentioned above [25].

## MATERIALS AND METHODS

### Study design

This cross-sectional assessment uses baseline data from GERAS-US, a 36-month, US-based, prospective, longitudinal cohort study of patients with clinician-diagnosed early AD seeking routine care for memory concerns. Patients were invited to participate in the study during routine visits with their healthcare provider. Patients and their study partners were enrolled from October 30, 2016, through October 9, 2017. Sites included 76 primary care and specialty care settings within the US, all of which completed Good Clinical Practice training prior to participant enrollment. Electronic tablets were used to collect baseline evaluations that included clinician interviews and study partner surveys. To increase the diagnostic certainty of studying individuals with early AD longitudinally, amyloid status was required. Those patients with evidence of amyloid were scheduled to continue assessments with their study partner every 6 months (±6 weeks) for up to 36 months. Patients and their study partners were remunerated for their time and travel, and sites were compensated based on market value. A central or site-specific institutional review board granted study approval.

### Participant selection and cohort designation

Eligible patients were 55 to 85 years old and met criteria for early AD in the opinion of the enrolling physician from whom they were receiving care for cognitive issues. Patients were required to have study partners that were willing to participate throughout the study. Patients were excluded from longitudinal evaluation if they had a negative Aβ PET scan or CSF results within the last 2 years, were participating or considering participation in an investigational drug clinical trial, or were employees or family members of personnel from the sites, sponsor, or third-party organizations affiliated with the study. All participants or their legal designees provided written informed consent before assessments and had to be able to communicate in English or Spanish.

Two outcome assessments were included in the screening process and cohort classification process. Patients with Mini-Mental State Examination (MMSE) [26] scores lower than 20 (out of 30) indicating lower cognitive status were excluded from the study. The literature varies as to how early stages of AD may be defined using the MMSE. Therefore, the Functional Activities Questionnaire (FAQ) was also administered to classify patients by severity. The FAQ is a study partner rating of the performance changes in complex activities of daily living (ADLs) [27]. It has been psychometrically tested to distinguish cut-points consistent with clinical diagnoses of MCI (MMSE≥24 and FAQ < 6) and MILD AD dementia (MMSE≥20 and FAQ≥6) [28]. For 26 of the 28 patients who fell outside of this range (i.e., MMSE≥24 and FAQ≥6), the enrolling physician’s current diagnosis was used to classify patients, and 2 patients were excluded from the analyses because they had diagnoses of “memory loss Not Elsewhere Classified.”

Determination of amyloid status was also required. Patients with prior evidence of amyloid via a Food and Drug Administration (FDA)-approved amyloid PET scan (florbetapir, flutemetamol, or florbetaben) or a CSF test were included in the study. Patients who did not undergo prior testing had to be willing and eligible to complete a florbetapir F18 PET scan in accordance with the FDA package insert. Scan results were to be shared with the patients and their study partners.

Participants were classified based on severity (MCI or MILD) and within each severity cohort by amyloid status ([+] or [−]), including MCI[+], MCI[−], MILD[+], and MILD[−].

### Assessments

Key assessments for this paper included healthcare resource utilization, caregiver burden, and economic burden. The entire listing of GERAS-US baseline and longitudinal measures is described elsewhere [25].

The Resource Utilization in Dementia (RUD version 4.0) [29] is a structured interview with the study partner to obtain healthcare resource utilization, work status, and living accommodations information for both the patient and the caregiver as well as items to determine the level of formal and informal care attributable to AD. Caregiving time included hours (averaged over in the previous month) spent assisting patients’ instrumental ADLs (iADLs) such as shopping, cooking, housekeeping, laundry, transportation, taking medication, and managing finances; basic ADLs (bADLs) such as using the toilet, eating, dressing, grooming, walking, and bathing; and providing supervision (i.e., preventing dangerous events) for the patient.

## ACKNOWLEDGMENTS

Writing support was provided by Teresa Tartaglione, PharmD (Synchrogenix, a Certara Company, Wilmington, DE, USA). The authors thank the following who provided support to the conduct of this study: the GERAS team (Rita Papen, Jose Luis Guerra, and Deanilee Deckard) and each of the study investigators, site personnel, patients, and study partners for their participation in this study.

Eli Lilly and Company is the sole sponsor and funder for this study; the sponsor was responsible for the study design, data collection, data analysis, interpretation of data, and decision to publish the findings.

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/19-1212r1).