Basal forebrain global functional connectivity is preserved in asymptomatic presenilin-1 E280A mutation carriers: Results from the Colombia cohort.

Abstract

Background: Imaging studies showed early atrophy of the cholinergic basal forebrain in prodromal sporadic Alzheimer's disease and reduced posterior basal forebrain functional connectivity in amyloid positive individuals with subjective cognitive decline. Similar investigations in familial cases of Alzheimer's disease are still lacking.

Objectives: To test whether presenilin-1 E280A mutation carriers have reduced basal forebrain functional connectivity and whether this is linked to amyloid pathology.

Design: This is a cross-sectional study that analyzes baseline functional imaging data.

Setting: We obtained data from the Colombia cohort Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial.

Participants: We analyzed data from 215 asymptomatic subjects carrying the presenilin-1 E280A mutation [64% female; 147 carriers (M = 35 years), 68 noncarriers (M = 40 years)].

Measurements: We extracted functional magnetic resonance imaging data using seed-based connectivity analysis to examine the anterior and posterior subdivisions of the basal forebrain. Subsequently, we performed a Bayesian Analysis of Covariance to assess the impact of carrier status on functional connectivity in relation to amyloid positivity. For comparison, we also investigated hippocampus connectivity.

Results: We found no effect of carrier status on anterior (Bayesian Factor₁₀ = 1.167) and posterior basal forebrain connectivity (Bayesian Factor₁₀ = 0.033). In carriers, we found no association of amyloid positivity with basal forebrain connectivity.

Conclusions: We falsified the hypothesis of basal forebrain connectivity reduction in preclinical mutation carriers with amyloid pathology. If replicated, these findings may not only confirm a discrepancy between familial and sporadic Alzheimer's disease, but also suggest new potential targets for future treatments.