Neuroimaging studies of MCI in PD
Structural imaging has been used primarily to differentiate PD from PD-D, AD, and DLB. As reviewed by Duncan et al. , inclusion of PD-MCI patients compared with PD and controls has been limited (there have been only four studies with more than 20 PD-MCI subjects since 2010). These studies cannot be readily compared because of different definitions of PD-MCI. Nevertheless, no consistent findings based on atrophy measures have been reported. Newer techniques such as diffusion tensor imaging (DTI) and white matter hyperintensity burden have not revealed any differences between PD-MCI and PD in small studies.
Single-photon emission computed tomography
Traditionally, 99mTc-hexamethylpropylene amine oxime (HMPAO) has been used to differentiate DLB and AD, based on the decreased occipital perfusion in DLB and [123I]-FP-CIT has been used to examine striatal dopamine transporter (DAT) loss. Only recently has DAT imaging with [123I]-FP-CIT been used to examine early PD cases longitudinally. In the largest study to date, 491 cases with disease duration of 2.06 years and a MMSE score of 29.3 at baseline had a significantly increased odds ratio of 3.3 (95% CI 1.7-6.7) for cognitive impairment defined as a Montreal Cognitive Assessment score of <26 if they were in the lowest quartile for striatal binding compared with the highest quartile. When MMSE < 24 was the outcome, the odds ratio associated with cognitive impairment was 7.6 (95% CI 0.8-68.4) for individuals in the lowest quartile for striatal binding. Change from baseline in imaging after 22 months was independently associated with motor, cognitive, and behavioural outcomes .
Positron emission tomography (PET)
18F-fluorodeoxyglucose (18FDG) PET has been used to demonstrate a PD-related cognitive pattern (PDCP) characterized by reductions in frontal and parietal association areas and increase in cerebellar vermis that is distinct from the PD-related motor pattern, is reproducible, and is unaltered by PD treatment . When compared with neuropsychological test scores, this pattern correlated with memory and executive performance and remained distinct from the PD-related motor pattern when 15 patients were followed over 48 months . In a subsequent study , differences in regional metabolism were analysed for a group of 51 PD patients categorized by MCI subtype. MCI was diagnosed if performance on one or more cognitive domains (executive, language, visuospatial, memory) fell at least 1.5 SD below normative values; patients were classified as having no impairment or single- or multiple-domain MCI. When compared with PD patients who were cognitively normal and healthy controls, multiple-domain MCI patients exhibited metabolic reductions in the inferior parietal lobe and middle frontal gyrus, whereas patients with single-domain MCI did not differ from controls or cognitively normal PD patients. Hypermetabolism was found in the pons and cerebellum for all three MCI groups, which may indicate a compensatory response to dopaminergic deficiency in the striatum. In a new study , correlation between a single cluster in the caudate nucleus based on DAT binding and expression of the broadly distributed PDCP network points to the relevance of nigral dopaminergic input to the caudate. The study raised the possibility that both reduced dopaminergic input and the PDCP network play a role in cognitive impairment, possibly interacting with other neurotransmitter deficiencies, for example in the cholinergic system.