Longitudinal lumbar puncture adherence in the Alzheimer’s Prevention Initiative Autosomal‐Dominant Alzheimer’s Disease Colombia Trial

Abstract

Background: Cerebrospinal fluid (CSF) biomarkers have potentially important roles in Alzheimer’s disease (AD) treatment and prevention trials. The Alzheimer’s Prevention Initiative Autosomal‐Dominant AD (API ADAD) trial protocol (NCT01998841) includes optional CSF biomarker measurements at baseline, 24 months, and 60 months. We determined the adherence to lumbar puncture (LP) procedures and predictors of dropout rates in trial participants who had a baseline LP. Method: Available data from cognitively unimpaired 30–60‐year‐old members of the Presenilin 1 E280A kindred were used to characterize LP participation rates at baseline, LP‐related complications and potential factors associated with adherence to 24‐month follow‐up LPs (age, sex, education, place of residence, puncture site, needle gauge, number of attempts, and traumatic puncture). Logistic regression was used to investigate associations. Result: 130 (51.6%) of 252 trial individuals consented to participate in the CSF biomarkers substudy. Consent was not associated with age, sex, education or location of residence. 43 (33.1%) participants had 49 LP‐related complications at baseline. The most frequent complications were headache in 25 (19.2%) participants and low back pain in 14 (10,8%) participants. Other baseline LP‐related events were dizziness, photopsia, and tremor. Complications at baseline were not associated with puncture site (L3‐L4 or L4‐L5), needle gauge (22 or 24 G), number of attempts or traumatic puncture. Ninety‐eight (75.4%) of the eligible participants consented to have the 24‐month follow‐up LP. Absence of any baseline LP‐related complications was associated with less attrition in this subsequent LP consent (0R = 0.25; 95%CI 0.10‐0.61), after controlling for age, sex, years of schooling, rural home and city of residence. Conclusion: Adherence to 24‐month follow‐up LP in API ADAD trial was 75.4%. This clinical trial is conducted in young people, active at work. Although some participants live far from the city where LP’s are performed or in remote areas, this did not affect their willingness to consent to a second LP. However, the presence of any complication did increase the risk of withdrawal for the subsequent procedure since it impacted ability to work. This information could help to inform the design and statistical power of future AD prevention trials using CSF biomarker endpoints.