Structural MRI of the basal forebrain as predictor of cognitive response to galantamine in healthy older adults: A randomized controlled double‐blinded crossover study

Abstract

Background Cholinesterase inhibitors (e.g. galantamine) can enhance cognitive functions in healthy elderly and delay cognitive decline in patients with Alzheimer`s diseases (AD). However, not everyone benefits from this treatment (non‐responders). Current studies show clinical meaningful improvements only in one third of AD patients treated with cholinesterase inhibitors. In this context, predictors of drug response could optimize AD treatment by identifying non‐responders and protect these patients from common adverse side effects. Method Here, we investigate structural MRI of the basal forebrain cholinergic system volume (BFvol) as a potential predictor of cognitive response to a single dose of galantamine in healthy adults (n=18; 59‐75 years). Result We observed that the cognitive response to galantamine, more specifically the attention‐dependent filtering performance in a delayed match‐to‐sample working memory task, correlated with BFvol: Only participants with high BFvol showed a significant positive effect of galantamine on the ability to filter out distracting information during the working memory encoding process. Conclusion Our results indicate that BFvol could be a predictor of galantamine response in healthy elderly. Future studies need to assess whether BFvol may serve as a predictor of the galantamine response in AD patients, too.

Structural (dys)connectivity associates with cholinergic cell density of the nucleus basalis of Meynert in Alzheimer’s disease

“…Specifically parahippocampal acetylcholine activity plays a role in mediating memory encoding and consolidation 67,70 . This shows the crucial role of temporal cholinergic projections in supporting memory-related circuitry in the medial temporal lobe, which is clinically relevant in amnestic Alzheimer's disease 12,13,71 .…”

“…Aβ and NFT accumulation has been associated with cholinergic cell loss in the NbM, which in turn associated with decreased cortical acetylcholine and plays an important role in disease-related cognitive decline, specifically in memory and attention processing [5][6][7][8][9][10][11] . Neuroimaging of the NbM has shown to be useful, for instance NbM volume can predict cognitive improvement after intake of galantamine, a common drug treatment targeting the cholinergic system in Alzheimer's disease 12 . Moreover, deep brain stimulation of the NbM is explored as a possible treatment option in Alzheimer's disease, by restoring the cholinergic transmission that is crucial in mediating memory processing [13][14][15] .…”

Modes of Acetylcholine Signaling in the Prefrontal Cortex: Implications for Cholinergic Dysfunction and Disorders

“…Furthermore, cholinesterase inhibitor therapy in AD improves cognitive performance by increasing the activation of frontal cortical circuits as determined by fMRI studies [94,95]. However, only a subset of patients with AD is effectively responsive to AChE inhibitors, and cholinergic basal forebrain integrity is a key predictor of treatment success [96].…”