Basal forebrain volume and metabolism in carriers of the Colombian mutation for autosomal dominant Alzheimer's disease

Abstract

We aimed to study atrophy and glucose metabolism of the cholinergic basal forebrain in non-demented mutation carriers for autosomal dominant Alzheimer's disease (ADAD). We determined the level of evidence for or against atrophy and impaired metabolism of the basal forebrain in 167 non-demented carriers of the Colombian PSEN1 E280A mutation and 75 age- and sex-matched non-mutation carriers of the same kindred using a Bayesian analysis framework. We analyzed baseline MRI, amyloid PET, and FDG-PET scans of the Alzheimer's Prevention Initiative ADAD Colombia Trial. We found moderate evidence against an association of carrier status with basal forebrain volume (Bayes factor (BF₁₀) = 0.182). We found moderate evidence against a difference of basal forebrain metabolism (BF₁₀ = 0.167). There was only inconclusive evidence for an association between basal forebrain volume and delayed memory and attention (BF₁₀ = 0.884 and 0.184, respectively), and between basal forebrain volume and global amyloid load (BF₁₀ = 2.1). Our results distinguish PSEN1 E280A mutation carriers from sporadic AD cases in which cholinergic involvement of the basal forebrain is already detectable in the preclinical and prodromal stages. This indicates an important difference between ADAD and sporadic AD in terms of pathogenesis and potential treatment targets.