Basal forebrain atrophy is a presymptomatic marker for Alzheimer's disease

Abstract

Background-Alzheimer's disease (AD) is the most common degenerative neurological disorder. The onset of symptoms is insidious and follows a long period of progression of an asymptomatic pathology that proceeds in a precise anatomical and temporal sequence (1-3). Recent studies using quantitative MRI techniques have shown the localization of the in vivo pathology of AD and it's antecedent, Mild Cognitive Impairment (MCI) (4). The objective of the present study was to determine whether a sensitive and reliable marker for the presymptomatic phase of the disorder could be identified by longitudinal analysis of an initially asymptomatic, community-based population.

Grey matter atrophy of basal forebrain and hippocampus in mild cognitive impairment

“…Clinical treatment of Alzheimer's disease with acetylcholinesterase inhibitors has shown that the cholinergic neurotransmission increase can reduce hippocampal atrophy and ameliorate the symptoms of dementia 35 36. Recently, a longitudinal study shed light on the temporal sequence of the pathological process of the two ROIs in the progression of AD in a 5–6 year interval 18. Their results showed that atrophy in the BFA preceded the emergence of clinical symptoms by 4.5 years, and that the atrophy of the left hippocampus was prognostic of dementia.…”

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

“…In these studies, magnetic resonance imaging (MRI) methods were used to detect structural changes associated with atrophy of the basal forebrain, particularly in the posterior regions (Grothe et al, 2011), these changes being correlated with cognitive decline in clinical cohorts of patients diagnosed with Alzheimer's disease or its prodromal stage, mild cognitive impairment (MCI). In some cases, basal forebrain atrophy was observed as early as 4.5 years before the onset of overt clinical symptoms (Hall et al, 2008).…”

Does basal forebrain atrophy mediate or moderate the effect of hippocampal atrophy on the risk for mild cognitive impairment?

“…We5 have found that BFA atrophy in individuals who develop AD within 2–4 years was necessary but not sufficient for this rapid transition. While BFA atrophy was a marker of impending dementia, we hypothesised that hippocampal atrophy was necessary for the clinical transition to occur.…”