Parkinson’s disease (PD) is a neurodegenerative disease associated with the progressive loss of dopamine neurons, and incidence studies suggest that an annual rate of 10% of PD patients develop dementia (which is sometimes termed Parkinson’s disease with dementia (PDD))¹. Accurate and comprehensive knowledge of the rate of disease deterioration is essential for the design and evaluation of new therapies for this disorder. Although enormous progress has been made in the treatment of PD², the association between the direct effects of dopaminergic therapies on brain global/regional perfusion and disease status remains unclear. Arterial spin labelling (ASL) is a non-invasive MRI perfusion tool that quantitatively measures cerebral blood flow (CBF) per unit of tissue mass by taking advantage of arterial water as a freely diffusible tracer³. The ability to obtain quantification on an absolute scale further allows for easy recognition of diffuse hypoxic/anoxic states and also for assessments of cortical perfusion before and after a given intervention. We had three a priori hypotheses for our study: (a) that ASL-MRI would indicate cortical hypoperfusion in the subjects with PD and PDD as compared with the normal controls; (b) that dopaminergic therapy might alter acute CBF changes in particular brain regions in PD and PDD; and (c) that differences in regional perfusion resulting from pharmaceutical effects would predict the baseline or interval changes indicated during clinical evaluations. Our results might help prove the utility of ASL in defining a time window for early interventions against PD.Thirty-four right-handed PD and PDD patients (13 men and 21 women, mean age: 62.18 ± 9.1 years) were prospectively enrolled in this study. All the patients completed two tests corresponding to the ON and OFF medication states. For the ON testing, the study procedures began 1 h after the patient had taken their daily dopaminergic medications, while OFF state is withdrawal of dopaminergic medications 12–18 h prior to scanning. MRI acquisition was performed on 1.5T clinical scanner (Discovery 450, GE Healthcare, Milwaukee, USA) using an 8-channel brain coil as the signal detection and whole body coil for RF transmission. T1-weighted images were acquired using the three-dimensional fluid-attenuated IR FSPGR with the following imaging parameters: TR =9.5 ms, TE =3.9 ms, TI =450 ms, flip angle =20, FOV =256×256 mm, matrix size =512×512, number of slices =110, and slice thickness =1.3 mm. ASL images were acquired using a pseudo-continuous ASL technique with a 3D spiral FSE readout. The imaging parameters used were TR= 4548 ms, postlabel delay= 1525 ms, TE= 10.5 ms, matrix size= 128×128, NEX= 3, number of slices =38, slice thickness =4.0 mm (with whole brain coverage), and total acquisition time =4 minutes. For each subject, a CBF map was calculated by scanner console with FuncTool 3DASL (GE Healthcare) within 1 minute and was reported in ml/100gm/min units. Imaging data were preprocessed using FSL v5.0 (Functional MRI of the Brain Software Library) and SPM8 (Statistical Parametric Mapping, Wellcome Department of Imaging Neuroscience, London, UK) implemented in Matlab 7.3 (MathWorks, Natick, MA, USA).The voxel-wise analysis of the absolute CBF maps revealed no significant perfusion deficits in the PD_OFF patient group, compared to normal control (Table 1 and Figure 1a). Bilateral perfusion decreases were found in the frontal, parietal, and cerebellar regions in the PDD_OFF group (Table 1 and Figure 1b). For the PD_ON patient group, the absolute CBF maps revealed significant perfusion deficits in the occipital lobes, parietal lobes, and cerebellum that were not found before the administration of dopaminergic medications (Table 1 and Figure 1c). The CBF patterns in the PDD_ON patients also demonstrated similar but more widespread neo-cortical hypoperfusion patterns than those found in the PD_OFF patients (Table 1 and Figure 1d). Decreased perfusion was also found in subcortical regions. Compared with the PD patients, the PDD patients had significantly lower CBF values in the frontal lobe, including the medial, inferior, paracentral, and superior frontal lobe regions. The PDD group also exhibited lower CBF in the parahippocampus, anterior cingulate, and precuneus (Figure 2a). A comparison of the PD_ON and PDD_ON groups found no significant differences in CBF for the various brain regions (Figure 2b).We non-invasively explored PD- and PDD-related cortical blood flows via ASL. The perfusion patterns were characterized by extensively decreased neocortical and preserved subcortical perfusion. The development of dementia in PD further worsens the perfusion status. In addition, the highly sensitive temporal responses to the direct effect of dopaminergic medications shown by ASL allow clinicians and researchers to easily, safely, and effectively quantify the absolute perfusion values.