Commentary on: Association of imaging abnormalities of the subcallosal septal area with Alzheimer's disease and mild cognitive impairment

Gan et al. 1 describe the use of a simple linear measurement of the distance between the septal nuclei — the inter-septal distance (ISD) — in the basal forebrain as a sensitive and specific predictor of memory problems in a consecutive sample of hospital patients having brain computed tomography (CT). This is a novel and interesting finding and is based on the primary neuropathology of Alzheimer's Disease (AD), which, in addition to atrophy of the entorhinal cortex and hippocampus, is associated early in the disease course with basal forebrain atrophy. The basal forebrain consists of the nucleus accumbens, nucleus basilis (of Meynert), the diagonal band (of Broca), the substantia innominate, and the medially placed septal nuclei.2 These structures, which are located inferior to the head of the caudate and superior to the hypothalamus, are the main source of acetyl choline in the brain, a system that is known to fail in AD. The basal forebrain is highly interconnected with the hippocampi and entorhinal cortex. It is thus biologically plausible that atrophy of these structures, with resultant widening of the distance between the septal nuclei, might be an imaging feature of AD.