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

Combined Functional Neuroimaging With Genotyping

Functional MRI of patients stratified for genes known to be implicated in Parkinson's dementia provides important insights into potential underlying substrates of cognitive heterogeneity in Parkinson's disease. For example, Winder-Rhodes et al. (2015) used event-related functional MRI to measure brain activations during a memory test involving picture encoding. They related common microtubule associated protein tau (MAPT) haplotypes to memory function and showed that hippocampal activation was lower in MAPT H1 homozygotes than in H2 carriers. Nombela and co-workers (2014) examined the effects of common variants implicated in Parkinson's disease cognition on neural activity during tasks specific to three separate cognitive domains: visuospatial performance, executive functions and memory. Their visuospatial mental rotation task revealed reduced parietal activation and impaired visuospatial performance particularly for MAPT H1 homozygotes. Intriguingly, they found a relationship between COMT met/met homozygotes and executive function in prefrontal cortex and caudate that was strongly related to dopamine dose. They found no relationship between COMT or MAPT and neural activity during the memory task, but noted an association between APOE4 allele carrier status and temporo-parietal activation during this task. Two earlier studies by the same group showed underactivation in a fronto-parietal network in COMT met/met homozygotes during attentional control and planning tasks (Williams-Gray et al., 2007, 2008). These combined neuroimaging and genotyping studies provide evidence for neurochemical and neuropathological underpinnings for the two distinct patterns of cognitive dysfunction in Parkinson's disease. COMT-associated changes in fronto-parietal regions point to dopaminergic networks and MAPT-linked visuospatial and hippocampal deficits implicate tau involvement in Parkinson's patients with prominent posterior cortical changes.