Neural correlates of early cognitive dysfunction in Parkinson's disease

Abstract

Objective Dementia is a common and feared aspect of Parkinson's disease but there are no robust predictors of cognitive outcome. Visuoperceptual deficits are linked to risk of dementia in Parkinson's disease but whether they predict cognitive change is not known, and the neural substrates of visuoperceptual dysfunction in Parkinson's have not yet been identified. Methods We compared patients with Parkinson's disease and unaffected controls who underwent BOLD fMRI while performing our previously validated visuoperceptual task and tested how functional connectivity between task‐specific regions and the rest of the brain differed between patients who performed well and poorly in the task. Results We show that task performance at baseline predicts change in cognition in Parkinson's disease after 1 year. Our task‐based fMRI study showed that the performance in this task is associated with activity in the posterior cingulate cortex/precuneus. We found that functional connectivity between this region and dorsomedial prefrontal cortex was reduced in poor performers compared with good performers of this task. Interpretation Our findings suggest that functional connectivity is reduced between posterior and anterior hubs of the default mode network in Parkinson's patients who are likely to progress to worsening cognitive dysfunction. Our work implicates posterior default mode nodes and their connections as key brain regions in early stages of dementia in Parkinson's disease.

Brain iron deposition is linked with cognitive severity in Parkinson’s disease

“…Recently, risk algorithms combined clinical information to predict cognitive change over time 23. Visual changes are also emerging as early markers of cognitive change in PD 24. Whether structural brain changes are more strongly linked with clinical risk scores or visual deficits before onset of dementia is not yet known.…”

Fiber-specific white matter reductions in Parkinson hallucinations and visual dysfunction

“…There is growing evidence that visuoperceptual deficits are an early indicator of PD dementia, 1 and we have previously shown that visuoperceptual deficits are linked to cognitive decline after 1 year. 6 By examining the differences in white matter connectivity in patients with PD and low visual performance and using a novel, more sensitive technique, we have highlighted additional white matter tracts that are affected in the earliest stages of cognitive impairment.…”

“…Our results are also in keeping with other neuroimaging studies highlighting the importance of connectivity changes in early cognitive impairment of PD. Changes in functional connectivity between visuospatial and frontal regions 42 and between the posterior cingulate with frontal regions 6,42 are seen in patients with PD and early cognitive impairment. We have also shown changes within the left fronto-occipital fasciculus, an association tract thought to play a role in executive function, semantic language, and visual processing.…”

“…The patients with PD were also classified into high visual performers (n = 70) and low visual performers (n = 34) on the basis of performance on 2 visual computer tasks (Cats-and-Dogs task and Biological Motion task). Details of stimulus generation and experimental procedures have been described previously 6,7,16 (example stimuli are available from Figshare, supplemental figure 1, figshare.com/s/1ff87201e92924f488f2). For both tasks, performance was measured in terms of discrimination sensitivity; participants who performed worse than the group median performance on both tasks were classified as low visual performers.…”

“…4 Similarly, visual processing abnormalities are associated with higher risk: poor color vision is linked to Parkinson dementia, 5 and impaired visual performance correlates with poor cognition at the 1-year follow-up. 6,7 The neural substrates of hallucinations and visual dysfunction therefore provide important insights into early Parkinson dementia.…”