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

Disclosures

Brain. 2018;141(9):2545-2560. 

In This Article

Event-related Functional MRI

Event-related functional MRI can be a sensitive indicator of presymptomatic cognitive dysfunction as it may reveal changes in blood oxygen level-dependent signals, reflecting altered patterns of neuronal activity, before gross structural changes are seen. Several groups have shown reduced activation in fronto-parietal regions including ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC) and caudate in Parkinson's patients compared with controls, during executive tasks (Monchi, 2004; Monchi et al., 2007; Baglio et al., 2011; Gawrys et al., 2014; Gerrits et al., 2015; Trujillo et al., 2015). However, these studies did not distinguish between different levels of cognitive function amongst patients with Parkinson's disease.

Lewis et al. (2003) used performance in an executive task (the Tower of London task) to differentiate cognitive function within patients with Parkinson's disease. They found that patients with poorer executive performance showed reduced activity in VLPFC, DLPFC and caudate whilst performing a memory task. Interestingly, during executive task performance, prefrontal cortex and caudate activities show a non-linear relationship between disease severity and activation, which relates to dopamine treatment (Rowe et al., 2008). Nagano-Saito (2014) showed reduced activity in VLPFC, DLPFC and caudate whilst planning set-shifting, in PD-MCI compared with Parkinson's disease and no cognitive involvement. During a memory task, PD-MCI patients showed reduced activity in anterior cingulate and caudate compared with Parkinson's disease patients without cognitive involvement. Importantly, they also showed that dopamine transporter binding correlated with blood oxygen level-dependent activity in caudate, suggesting a neurochemical substrate for these changes. However, working memory and executive deficits—caused by dysfunction in fronto-striatal networks—are not necessarily a precursor of dementia in Parkinson's disease. Therefore, these studies, whilst sensitive to executive dysfunction, may not be the most useful in identifying the earliest networks linked to Parkinson's dementia. It is instructive that one group (Baglio et al., 2011) showed additional reduced activation in occipital regions in Parkinson's disease, even during an executive task, suggesting that changes in occipital lobe activity may reflect preclinical cognitive dysfunction.

Despite evidence for the importance of visuospatial deficits as early precursors of cognitive dysfunction, there are few event-related functional MRI studies examining changes in brain activity related to visuo-spatial dysfunction in Parkinson's disease, and those that do are focused on visual hallucinations. For example, Meppelink et al. (2009) showed reduced blood oxygen level-dependent activity in lateral occipital cortex in patients with Parkinson's disease in the seconds before an image was recognized, but how this relates to cognitive dysfunction was not explored. Nemcova et al. (2017) showed reduced activation during an object-viewing task in the superior parietal lobe in PD-MCI compared with Parkinson's disease patients with normal cognition. Interestingly, the two groups did not differ in task accuracy, suggesting that altered activation in this brain region may precede loss of visuo-spatial function.

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