Changes in neurotransmitter-related functional connectivity along the Alzheimer’s disease continuum

Abstract

Alzheimer’s disease (AD) may be associated with early dopamine (DA) dysfunction. However, its effects on neurofunctional alterations in the neurotransmission pathways remain elusive. In this study, PET atlases and functional MRI data for 86 older adults with mild cognitive impairment (AD-MCI), 58 with mild AD dementia and 76 cognitively unimpaired (CU) were combined to investigate connectivity alterations associated with the dopaminergic and cholinergic (ACh) systems. A cross-sectional design was used to compare neurotransmitter-related functional connectivity across groups and associations between functional connectivity and cognitive performance.

The findings show that the AD-dementia group showed a decline in mesocorticolimbic DA-related connectivity in the precuneus but heightened connectivity in the thalamus, whereas the AD-MCI group showed a decline in nigrostriatal connectivity in the left temporal areas. ACh-related connectivity decline was observed in both AD-MCI and AD-dementia primarily in the temporo-parietal areas. Episodic memory scores correlated positively with ACh- and DA-related connectivity in the temporo-parietal cortex and negatively with DA-related FC in the fronto-thalamic areas. This study shows that connectivity alterations in ACh and DA functional pathways parallel cognitive decline in AD and might be a clinically relevant marker in early AD.