Risk reduction and precision prevention across the Alzheimer's disease continuum: a systematic review of clinical trials combining multidomain lifestyle interventions and pharmacological or nutraceutical approaches.

A phase III clinical trial of Tramiprosate in AD patients failed to meet the primary efficacy endpoints, but a subgroup analysis revealed significant cognitive improvements, measured by ADAS-Cog scores, and a positive trend on CDR-SB, in APOE -ε4 homozygous participants with milder cognitive decline [ 56 ].

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In PENSA trial, combining lifestyle intervention with EGCG showed a trend toward cognitive improvement that became significant after a three month washout, indicating potential long term benefits in APOE -ε4 carriers with SCD [ 51 ].

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Results were published after the first phase of the 20-week randomized controlled part of the study, with significant changes reported (albeit with 1-tailed statistical tests) on most primary cognitive outcomes on CGIC, CDR-SB and CDR Global tests, along with borderline significance in the ADAS-Cog test ( Table 2 ).

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