The Cost-Effectiveness of Three Prevention Strategies in Alzheimer's Disease: Results from the Multidomain Alzheimer Preventive Trial (MAPT)

BACKGROUND: To date, no curative treatment is available for Alzheimer’s disease (AD). Therefore, efforts should focus on prevention strategies to improve the efficiency of healthcare systems. Objective: Our aim was to assess the cost-effectiveness of three preventive strategies for AD compared to a placebo. Design: The Multidomain Alzheimer Preventive Trial (MAPT) study was a multicenter, randomized, placebo-controlled superiority trial with four parallel groups, including three intervention groups (one group with Multidomain Intervention (MI) plus a placebo, one group with Polyunsaturated Fatty Acids (PFA), one group with a combination of PFA and MI) and one placebo group. Setting: Participants were recruited and included in 13 memory centers in France and Monaco. Participants: Community-dwelling subject aged 70 years and older were followed during 3 years. Interventions: We used data from the MAPT study which aims to test the efficacy of a MI along PFA, the MI plus a placebo, PFA alone, or a placebo alone. Measurement: Direct medical and non-medical costs were calculated from a payer’s perspective during the 3 years of follow-up. The base case incremental Cost-Effectiveness Ratio (ICER) represents the cost per improved cognitive Z-score point. Sensitivity analyses were performed using different interpretation of the effectiveness criteria. Results: Analyses were conducted on 1,525 participants. The ICER at year 3 that compares the MI + PFA and the MI alone to the placebo amounted to €21,443 and €21,543 respectively, per improved Z score point. PFA alone amounted to €111,720 per improved Z score point. Conclusion: Our study shows that ICERS of PFA combined with MI and MI alone amounted to €21,443 and €21,543 respectively per improved Z score point compared to the placebo and are below the WTP of €50,000 while the ICER of PFA alone amounted to €111,720 per improved Z score point. This information may help decision makers and serve as a basis for the implementation of a lifetime decision analytic model.

Abstract 16476: Visit-to-Visit Blood Pressure Variability is Associated With Incident Frailty: The Multidomain Alzheimer Preventive Trial (MAPT)

Introduction: Visit-to-visit blood pressure variability (BPV) has been associated with greater cardiovascular and all-cause mortality, cognitive impairment, and incident dementia. It may also represent a decline in homeostatic mechanisms in blood pressure (BP) regulation associated with frailty, one of the most problematic expression of population aging. Hypothesis: We hypothesized that visit-to-visit systolic (SBPV), diastolic (DBPV), mean arterial (MAPV) and pulse pressure (PPV) variability are associated with greater incident frailty. Methods: We included 1,394 non-frail community-dwelling participants aged ≥ 70 years from the Multidomain Alzheimer Preventive Trial (MAPT) who underwent repeated clinical examinations over a 5-year follow-up period. SBPV, DBPV, MAPV and PPV were evaluated using standard deviation, coefficient of variation (CV), average real variability, successive variation, variation independent of mean and residual standard deviation. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Results: Higher SBPV was significantly associated with increased risk of incident frailty (1-sd increase of CV: HR = 1.18, 95% CI [1.02-1.37], p=0.03) after adjustment for demographics, body mass index, stroke, ischemic heart disease, diabetes, heart failure, antihypertensive drugs, systolic BP, MAPT intervention groups and baseline pre-frail status. Similar results were observed with all indicators of variability. DBPV and MAPV were not associated with incident frailty (p=0.6 and p=0.2, respectively). Interestingly, higher PPV was also associated with a greater risk of developing frailty over time (1-sd increase of CV: HR = 1.17, 95% CI [1.01-1.35], p=0.03). Conclusion: Independently of BP, higher SBPV and PPV are major clinical predictors of incident frailty. Our findings support the concept of BP physiological dysregulation underlying the frail state and suggest that controlling BP instability could be a promising interventional target in preventing frailty.

Cross-Sectional and Longitudinal Associations Between Plasma Neurodegenerative Biomarkers and Physical Performance Among Community-Dwelling Older Adults

Background Plasma amyloid-beta (Aβ), neurofilament light chain (NfL), and progranulin (PGRN) have been related to multiple neurodegenerative conditions that might affect physical performance. The aim of this study was to explore the relationship between these plasma neurodegenerative markers and physical performance among community-dwelling older adults. Methods Five hundred and seven older adults (aged 76 ± 5 years) previously recruited in the Multidomain Alzheimer’s Preventive Trial, and had received blood and physical performance tests, were included in this study. Plasma Aβ (Aβ 42/Aβ 40 ratio), NfL, and PGRN levels were measured. Physical performance was assessed by handgrip strength and the Short Physical Performance Battery (combining gait speed, chair stands, and balance tests). Physical performance measured at the same time point and after the blood tests were used. Mixed-effect linear models were performed with age, sex, allocation to Multidomain Alzheimer’s Preventive Trial group, body mass index, and Mini-Mental State Examination score as covariates. Results The mean values of Aβ 42/Aβ 40 ratio, NfL, and PGRN were 0.11, 84.06 pg/mL, and 45.43 ng/mL, respectively. At the cross-sectional level, higher plasma NfL was associated with a lower Short Physical Performance Battery score (β = −0.004, 95% CI [−0.007, −0.001]). At the longitudinal level, higher PGRN levels were associated with decreasing handgrip strength over time (β = −0.02, 95% CI [−0.04, −0.007]). All the other associations were statistically nonsignificant. Conclusion Our findings suggest the possibility of using plasma NfL and PGRN as markers of physical performance in older adults.