Imagine the brain as a complex highway system, with different networks responsible for different functions. Alzheimer’s disease (AD) wreaks havoc on this intricate network, causing cognitive decline. Scientists have been studying how acetylcholinesterase inhibitors (AChEIs), a type of medication used to treat AD, impact the brain’s resting-state networks (RSNs). In this pilot study, researchers used resting-state functional magnetic resonance imaging (rs-fMRI) to observe changes in the dorsal attention network of AD patients after AChEI therapy. The results showed that patients who responded well to AChEI therapy demonstrated increased connectivity within the dorsal attention network, which is involved in attention and focus. Interestingly, it was also discovered that the dorsal attention network had negative functional connectivity with a specific area of the brain called the right planum temporale, before the therapy. This finding suggests that decreased connectivity between these two areas could be a biomarker for assessing the effectiveness of AChEIs in treating AD. This study opens up new possibilities for understanding the long-term effects of AChEIs and developing targeted therapies for Alzheimer’s patients.

BackgroundAlzheimer’s disease (AD) is the most common condition of all neurodegenerative diseases and is characterized by various cognitive dysfunctions. Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed the physiological dynamics of functionally connected brain networks, which are called resting-state networks (RSNs). Associations between impairments of RSNs and various neuropsychiatric diseases, such as AD, have been reported. Acetylcholinesterase inhibitors (AChEIs) have been used as a pharmacological treatment for mild-to-moderate moderate AD, and short-term improvements in cognitive functions and RSNs in restricted areas have been reported.ObjectiveWe aimed to characterize AChEI-related RSN changes by acquiring two sets of rs-fMRI data separated by approximately 3 to 6 months.MethodsSeventeen patients with AD and nine healthy subjects participated in this study. Independent component analysis was performed on the rs-fMRI data of AChEI-responsive and non-responsive AD patients, stratified according to change in Mini-Mental State Examination (MMSE) scores after 3 to 6 months of AChEI therapy. In addition, a region of interest-based analysis of the rs-fMRI data before therapy was performed to explore the functional connectivity (FC) changes associated with AchEI therapy.ResultsResponders showed a significantly greater increase in MMSE scores, especially for orientation for time, than that of non-responders following AChEI therapy. A subtraction map of MMSE score differences (responders minus non-responders) in the independent component analysis revealed higher FC of the dorsal attention network in responders compared with that in non-responders. Moreover, in the region of interest analysis of untreated status data, the dorsal attention network showed significant negative FC with the right planum temporale, which belongs to the ventral attention network, proportional to MMSE score change.ConclusionThe negative correlation of the FC of the dorsal attention network and right planum temporale before AChEI therapy and MMSE score change may be a biomarker of the therapeutic effect of AChEIs for AD.

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