Can Neuroimaging Predict Dementia in Parkinson's Disease?

Juliette H. Lanskey; Peter McColgan; Anette E. Schrag; Julio Acosta-Cabronero; Geraint Rees; Huw R. Morris; Rimona S. Weil


Brain. 2018;141(9):2545-2560. 

In This Article

Neuroimaging and Multimodal Predictors of Parkinson's Dementia

Recently, large-scale collaborations have enabled researchers to combine clinical, demographic, biological and genetic factors to determine predictors for Parkinson's dementia. Liu et al. (2017) developed a specific and sensitive algorithm for global cognitive impairment in a large dataset comprising over 3000 patients across nine cohorts. Their algorithm, which includes factors such as age at onset, gender, depression and motor scores, as well as baseline Mini-Mental State Examination, has the advantage of being cheap and non-invasive. It therefore has potential for widespread uptake for disease stratification. However, mean time from disease onset was >6 years. Neuroimaging has the potential to identify at-risk patients far earlier along the disease course and even before they exhibit reduced performance on standard cognitive tests. Other groups have combined clinical and neuroimaging measures in large-scale collaborations, capitalizing on the PPMI programme. Schrag and colleagues (2016) reported good accuracy (area under the curve 0.80) for an algorithm to predict cognitive impairment at 2 years combining clinical measures (excluding baseline cognitive score), CSF parameters and DAT SPECT imaging results at the time of diagnosis. Another recent study (Fereshtehnejad et al., 2017) used clinical, CSF and neuroimaging markers in a data-driven approach to stratify patients with Parkinson's disease into distinct clusters based on progression and showed a separate rapidly progressing diffuse malignant subtype. The neuroimaging measures in that study were deformation-based morphometry, a method of identifying disease-specific atrophy patterns, and SPECT imaging using a DAT tracer. Although comparisons between clinical subtypes did not survive multiple comparison testing, partly because neuroimaging was available in only a subset, the principle of applying these metrics in combination with other clinical measures shows important potential for defining Parkinson's subtypes. DAT SPECT imaging, structural MRI and DTI were also used in combination with other clinical and biological modalities by Caspell-Garcia (2017) to examine predictors of cognitive impairment. They showed that predictors of cognitive impairment were linked with dopamine deficiency (COMT and BDNF polymorphisms, and ipsilateral DAT availability). Although whether identified patients develop persistent dementia over time will need to be determined with longer follow-up. Decreased volume in widespread brain regions also predicted cognitive impairment, particularly in frontal, parietal, temporal and occipital regions. So far, these early findings in large longitudinal cohorts are relatively non-specific. They suggest that the right neuroimaging techniques, in combination with other multimodal measures, may have a role to predict the earliest stages of cognitive involvement, as well providing important insights into underlying pathophysiological mechanisms of Parkinson's dementia.