Disease progression and costs at the 3-year follow-up of the GERAS-US study

Abstract

Introduction: GERAS-US prospectively characterized clinical and economic outcomes of early symptomatic Alzheimer's disease (AD). Societal cost changes were examined in amyloid-positive patients with mild cognitive impairment due to AD (MCI) and mild dementia due to AD (MILD).

Methods: Cognition, function, and caregiver burden were assessed using Mini-Mental State Examination (MMSE), Cognitive Function Index (CFI), and Zarit Burden Interview, respectively. Costs are presented as least square mean for the overall population and for MCI versus MILD using mixed model repeated measures.

Results: MMSE score and CFI worsened. Total societal costs (dollars/month) for MCI and MILD, respectively, were higher at baseline ($2430 and $4063) but steady from 6 ($1977 and $3032) to 36 months ($2007 and $3392). Direct non-medical costs rose significantly for MILD. Caregiver burden was higher for MILD versus MCI at 12, 18, and 24 months.

Discussion: Function and cognition declined in MILD. Non-medical costs reflect the increasing impact of AD even in its early stages.

Highlights: In the GERAS-US study, total societal costs for patients with mild cognitive impairment due to Alzheimer's disease (MCI) and mild dementia due to Alzheimer's disease (MILD) were higher at baseline but steady from 6 to 36 months.Mini-Mental State Examination (MMSE) and Cognitive Function Index (CFI) worsened; the rate of decline was significant for patients with MILD but not for those with MCI.There was a rise in direct non-medical costs at 36 months for patients with MILD.Caregiver burden was higher for MILD versus MCI at 12, 18, and 24 months.Slowing the rate of disease progression in this early symptomatic population may allow patients to maintain their ability to carry out everyday activities longer.

Keywords: amyloid; dementia; mild cognitive impairment; societal burden.

FIGURE 1

Clinical outcome measures (actual scores) at baseline to 36 months in patients with amyloid [+] MCI and MILD. ^*Lower scores equal poorer status. ^†Higher scores equal poorer status. CFI, Cognitive Function Index; MCI, mild cognitive impairment due to Alzheimer's disease; MILD, mild dementia due to Alzheimer's disease; MMSE, Mini‐Mental State Examination; +, positive.

FIGURE 2

Total societal costs. Data were based on MMRM. The MMRM model was fitted at baseline, 6, 12, 18, 24, 30, and 36 months. Total societal costs were estimated on a 30‐day basis. Total societal costs (1‐month pre‐assessment) were calculated by summing the cost components at each time point. ^*A large increase in direct non‐medical costs for one MCI patient (structural changes to living accommodations costing 100,000 USD) drove total costs upward at 24 months, which then returned to the 6‐month levels by 36 months. The dashed line (—) represents the analysis with that patient removed. LS, least squares; MCI, mild cognitive impairment due to Alzheimer's disease; MILD, mild dementia due to Alzheimer's disease; MMRM, mixed‐model repeated measures; SE, standard error; USD, US dollar.

FIGURE 3

Patient and caregiver costs^a over 3 years^b in amyloid [+] MCI and MILD^c. ^aAll cost estimates are derived from the Resource Utilization in Dementia scale. Opportunity cost sums lost productive hours and multiplies them by national average annual gross hourly wage for workers and by lost leisure time for non‐workers (35% of hourly wage for workers). MMRM was used to estimate the cost by time and disease severity and their interaction in the model. The MMRM model was fitted at baseline, 6, 12, 18, 24, 30, and 36 months. ^bCalculated per 30‐day basis. ^cThe classification of MCI and MILD is based on the baseline assessment. NOTE: The spike in direct non‐medical costs at 24 months was due to costly structural changes/adaptations required for the home of one patient at $100,000. The dashed line (—) represents the analysis with that patient removed. LS, least squares; MCI, mild cognitive impairment due to Alzheimer's disease; MILD, mild dementia due to Alzheimer's disease; MMRM, mixed‐model repeated measures; PPPM, per person per month; USD, US dollars; +, positive.

FIGURE 4

A, Zarit Burden Interview (total score)—actual value. B, Resource Utilization in Dementia questionnaire (overall caregiver time)—actual value. Data were based on MMRM. Actual value = disease severity (SD) + time (as categorical) + SD × time; the values represent the LS mean estimate at time points (SE). *P < .001, †P < .01. LS, least squares; MCI, mild cognitive impairment due to Alzheimer's disease; MILD, mild dementia due to Alzheimer's disease; MMRM, mixed‐model repeated measures; SD, standard deviation; SE, standard error; ZBI, Zarit Burden Interview.