Leonardo Iaccarino, Arianna Sala, Silvia Paola Caminiti, Luca Presotto, Daniela Perani, Alzheimer’s Disease Neuroimaging Initiative
Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2020
Publication year: 2020

Abstract

Background:

Alzheimer’s disease (AD) is characterized by an involvement of brain dopamine (DA) circuitry, the presence of which has been associated with emergence of both neuropsychiatric symptoms and cognitive deficits.

Objective:

In order to investigate whether and how the DA pathways are involved in the pathophysiology of AD, we assessed by in vivo neuroimaging the structural and metabolic alterations of subcortical and cortical DA pathways and targets.

Methods:

We included 54 healthy control participants, 53 amyloid-positive subjects with mild cognitive impairment due to AD (MCI-AD), and 60 amyloid-positive patients with probable dementia due to AD (ADD) with structural 3T MRI and 18F-FDG-PET scans. We assessed MRI-based gray matter reductions in the MCI-AD and ADD groups within an anatomical a priori-defined Nigrostriatal and Mesocorticolimbic DA pathways, followed by 18F-FDG-PET metabolic connectivity analyses to evaluate network-level metabolic connectivity changes.

Results:

We found significant tissue loss in the Mesocorticolimbic over the Nigrostriatal pathway. Atrophy was evident in the ventral striatum, orbitofrontal cortex, and medial temporal lobe structures, and already plateaued in the MCI-AD stage. Degree of atrophy in Mesocorticolimbic regions positively correlated with the severity of depression, anxiety, and apathy in MCI-AD and ADD subgroups. Additionally, we observed significant alterations of metabolic connectivity between the ventral striatum and fronto-cingulate regions in ADD, but not in MCI-AD. There were no metabolic connectivity changes within the Nigrostriatal pathway.

Conclusion:

Our cross-sectional data support a clinically-meaningful, yet stage-dependent, involvement of the Mesocorticolimbic system in AD. Longitudinal and clinical correlation studies are needed to further establish the relevance of DA system involvement in AD.