Abstract
Objective: This clinical trial investigated the effects of a precision medicine intervention on cognition in asymptomatic and mildly symptomatic patients. Background: Multidomain approaches to treating modifiable risk factors in Alzheimer’s disease (AD) have shown cognitive benefits for patients at-risk for dementia. Design/Methods: Patients aged 25–86 were recruited from an Alzheimer’s prevention clinic and categorized into two groups. The prevention group (group 1) included normal cognition, subjective cognitive decline, and preclinical AD patients. The early treatment group (group 2) included predominantly MCI due to AD as well as mild AD dementia patients. Primary outcome was change in performance on a cognitive composite (m-APCC) measuring AD pathology in higher- versus lower-compliance participants at 18 months in groups 1 and 2. We also compared groups versus matched historical controls from NACC/Rush University. Secondary outcome was change in performance on a non-pathological cognitive aging composite (CAC). Trial registered at ClinicalTrials.gov (NCT03687710). Results: Of 202 participants screened, 178 met inclusion criteria; 154 (87%) had at least one post-baseline assessment and were included in analyses. Group 1 improved on the m-APCC by 0.426 at 18-months (p<0.0001). Similar effects were seen for higher and lower compliance groups (p=0.1467). Group 1 higher-compliance participants improved more than NACC (p=0.0039) and Rush controls (p=0.0133). Group 1 lower compliance participants also improved more than NACC (p=0.0105) and Rush (p=0.0259) controls. In group 2, higher compliance participants improved relative to lower compliance participants (p<0.0001) and NACC (p=0.0069), but not compared to Rush (p=0.3953). For group 1, the CAC improved by 2.67 years for higher-compliance participants and 3.52 years for lower-compliance participants (p=0.4039). Group 2 improved by 2.95 years in the CAC for higher-compliance participants and worsened by 5.06 years for lower-compliance participants (p=0.0004). Conclusions: Findings suggest a precision medicine multidomain intervention can improve cognitive function. Intervening earlier in the pre-AD dementia diagnostic spectrum led to greater improvements.