In vivo volumetry of the cholinergic basal forebrain

Abstract

Degeneration of cortically projecting acetylcholine-containing neuronal populations within the basal forebrain cholinergic system (BFCS) is a central pathogenetic aspect of Alzheimer’s disease (AD) and forms the rationale for the use of cholinomimetics as antidementive treatment. The role of the cholinergic deficit in AD pathophysiology has mainly been studied in experimental animal models and in neuropathologic examinations of human autopsy data of advanced disease stages. Interactions between cholinergic deficits and accumulation of cortical amyloid pathology point to a relevant role of BFCS degeneration for the preclinical stage of AD. The advent of novel computational morphometry techniques for the automated analysis of high-resolution MRI data allows studying AD-related atrophy in the living human brain with ever-increasing temporal and regional detail. Combining these morphometry techniques with recently developed stereotactic mappings of the BFCS provides a method for automated MRI-based volumetry that can sensitively assess degenerative changes of the BFCS in vivo. Here, we outline the general methodological approach for MRI-based BFCS volumetry and describe the specifics of different image processing choices and analysis strategies. We further discuss possibilities and limitations of this method for studying BFCS degeneration in the course of AD, with a special emphasis on using MRI-based BFCS volumetry as an imaging biomarker for defining the preclinical disease stage.