Biomarkers

Area of Science:

• Neuroscience
• Pharmacology
• Radiology

Background:

• Acetylcholinesterase inhibitors, like rivastigmine, are prescribed to slow cognitive decline in Alzheimer's disease (AD).
• The precise mechanisms by which these drugs affect brain activity and connectivity remain under investigation.
• This study focused on prodromal to mild AD patients to explore rivastigmine's impact on functional connectivity (FC) and cognition.

Purpose of the Study:

• To assess how rivastigmine treatment influences acetylcholine-related functional connectivity (FC) in patients with early-stage Alzheimer's disease (AD).
• To evaluate the impact of rivastigmine on cognitive performance in patients with prodromal to mild AD.
• To investigate the association between changes in FC and cognitive improvements following rivastigmine treatment.

Main Methods:

• Thirty-two patients with prodromal to mild AD were randomized into a 12-week rivastigmine treatment group (ADt) or an untreated control group (ADu).
• Neuropsychological tests and MRI scans were conducted at baseline and after 12 weeks.
• Functional MRI data were analyzed to map FC, specifically focusing on neurotransmitter receptor distributions (acetylcholine transporter, α4β2 nicotinic, M1 muscarinic receptors).

Main Results:

• The rivastigmine group (ADt) exhibited greater improvements in visual long-term memory compared to the control group (ADu).
• A significant reduction in frontal α4β2 nicotinic receptor-related FC was observed in the ADt group.
• Improvements in visual memory were significantly correlated with changes in α4β2-related FC.

Conclusions:

• Rivastigmine treatment led to functional connectivity changes in frontal and occipito-cerebellar regions in patients with early AD.
• These observed FC alterations were associated with concurrent improvements in long-term memory over the 12-week study period.
• Neurotransmitter-related FC serves as a potential MRI biomarker for assessing treatment mechanisms and tracking neuroplasticity in response to therapies targeting neurotransmitter systems in AD.