Striatal dopamine transporter uptake, parkinsonism and cognition in Alzheimer's disease

Abstract

Background and purpose: The correlates of motor parkinsonism in Alzheimer's disease (AD) remain controversial. The effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD were evaluated.

Methods: This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography, 18 F-florbetaben positron emission tomography, 3 T brain magnetic resonance imaging, and Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen and substantia nigra were quantified. The relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score and cognition was investigated using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates.

Results: Path analysis and multivariable GLMs for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness.

Conclusions: Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.