Discussion
This work suggests a significant benefit of combined interventions at 1 and 3 years only in the amyloid positive group. These effects were significant both in magnitude and statistically in the per protocol population. These findings indicate that future prevention trials could target amyloid positive non-demented individuals for interventions utilizing multi-domains. We have demonstrated the utility of a blood-based biomarker to determine amyloid status of individuals likely to respond to intervention. This could enable future prevention trials to have more rapid screening and to enroll many more positive amyloid participants. The blood-based biomarker also enables prevention trials in regions without access to amyloid PET or CSF analyses. We failed to reach significantly different cognitive effect of a prevention program in non-demented subjects according to amyloid blood status at 5 years, after 2 years off treatment, demonstrating that the intervention effect is not durable after 2-year discontinuation.Previously, in MAPT-AV45, we showed a cognitive impact of MI at 36 months in subjects with a positive amyloid PET and an association between MI and amyloid burden (lower in participants receiving MI) [