Valerie Bruemmer

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.

BACKGROUND: Alzheimer's disease (AD) is one of the costliest diseases in the United States. OBJECTIVE: To describe aspects of real-world patient and caregiver burden in patients with clinician-diagnosed early AD, including mild cognitive impairment (MCI) and mild dementia (MILD) due to AD. METHODS: Cross-sectional assessment of GERAS-US, a 36-month cohort study of patients seeking care for early AD. Eligible patients were categorized based on study-defined categories of MCI and MILD and by amyloid positivity [+] or negativity [-] within each severity cohort. Demographic characteristics, health-related outcomes, medical history, and caregiver burden by amyloid status are described. RESULTS: Of 1,198 patients with clinician-diagnosed early AD, 52% were amyloid[+]. For patients in both cohorts, amyloid[-] was more likely to occur in those with: delayed time to an AD-related diagnosis, higher rates of depression, poorer Bath Assessment of Subjective Quality of Life in Dementia scores, and Hispanic/Latino ethnicity (all p < 0.05). MILD[-] patients (versus MILD[+]) were more medically complex with greater rates of depression (55.7% versus 40.4%), sleep disorders (34.3% versus 26.5%), and obstructive pulmonary disease (11.8% versus 6.6%); and higher caregiver burden (Zarit Burden Interview) (all p < 0.05). MILD[+] patients had lower function according to the Functional Activities Questionnaire (p < 0.001), yet self-assessment of cognitive complaints across multiple measures did not differ by amyloid status in either severity cohort. CONCLUSIONS: Considerable patient and caregiver burden was observed in patients seeking care for memory concerns. Different patterns emerged when both disease severity and amyloid status were evaluated underscoring the need for further diagnostic assessment and care for patients.Study Registry:H8A-US-B004; ClinicalTrials.gov: NCT02951598.

INTRODUCTION: Research has shown increased health-care resource use (HRU) among patients with Alzheimer's disease and related disorders (ADRD) well before diagnosis, but the degree to which HRU is correlated with disease severity at the time of initial assessment is not well documented. METHODS: Retrospective analysis of linked medical records and claims data for three cohorts: mild ADRD (first [index] Mini-Mental State Examination [MMSE] ≥20), moderate/severe ADRD (index MMSE < 20), controls without cognitive impairment. HRU during the pre-index year was compared using multivariate regressions. RESULTS: < .01) higher HRU than controls. Compared to mild ADRD patients, moderate/severe ADRD patients had higher rates of hospitalizations (relative risk [RR]: 1.57), emergency department visits (RR: 1.36), potentially avoidable hospitalizations (RR: 1.72), and accidental falls (RR: 1.58). DISCUSSION: HRU before initial assessment increases with disease severity at the time of assessment, highlighting the need for timely evaluation and improved management in the earliest stages of ADRD.

GERAS-US aims to understand long-term clinical and economic outcomes of AD in the US. The current objective is to describe baseline findings by amyloid status and severity (mild cognitive impairment [MCI] and mild dementia [MILD]). GERAS-US is a 36-month, prospective study of patients aged 55 to 85 who enrolled from October 30, 2016, through October 9, 2017. Data collected included amyloid status, clinical assessments, and patient/study partner medical history, resource use, and health outcomes assessments. Cohorts were classified based on amyloid status (positive [+] or negative [-]) and severity (MCI: Mini-Mental State Examination [MMSE] 324, Functional Activities Questionnaire [FAQ] <6; MILD: MMSE 320, FAQ 36). Means (SD) and percentages are reported as of December 2017. Preliminary data included 87.7% of the final 1654 consented patient-study partner dyads. At interim, 259 were screen failures, 1372 had known severity (MCI=658, MILD=714), and 1147 had known amyloid findings (+=592, -=555), leaving 1144 for cross-classification (MCI+=281, MCI-=258, MILD+=311, MILD-=294). Patients’ average age was 70.4 years, and 55.1% were female. Study partners had a mean age of 58.6 years and were mostly female (65.7%), the sole caregiver (61.5%), and cohabitating with the patient (68.8%; 42.1% were spouses). Compared to MCI, MILD had poorer clinical characteristics/outcomes (Tables 1 and 2). Overall, MILD- had the highest rates of comorbidities, depression, and sleep disorders (Table 1), and the lowest patient-rated function and quality of life (Table 2). MILD+ had higher AD medication use and the lowest caregiver- and clinician-rated cognitive and functioning status (Tables 1 and 2). MILD- had the lowest rate of employment (7.8%), whereas MCI- had the highest rate of employment (23.3%) (Table 3). Total societal costs (1-month pre-baseline) were higher with increased severity (MCI: $2683, MILD: $4115) and amyloid negativity (+ $3223, - $3649) (Figure 1). Total Costs Across Cohortsa. MCI=mild cognitive impairment; MILD=mild dementia; USD=U.S. dollars; +=amyloid positive; -=amyloid negative. aTotal societal costs (1 month pre-baseline) were derived using opportunity costs. Using replacement costs resulted in lower costs including the cross-classified cohorts: MCI+ ($1661), MILD+ ($2195), MCI- ($2200), MLD- ($2303); severity cohorts: MCI ($1855), MILD ($2322), and amyloid status cohorts: + ($1942), - ($2243). Considerable clinical and economic burden was observed in early stages of AD. Differences were seen in cost and comorbidity in amyloid +/- cohorts, which underscores the need for accurate diagnosis and treatment in patients with cognitive impairment. Future GERAS-US data will aid in understanding the impact of early stage AD on patients, caregivers, and society.