Risk factors for early psychosis in PD: insights from the Parkinson's Progression Markers Initiative

Abstract

Background: Parkinson's Disease (PD) psychosis refers to the spectrum of illusions, formed hallucinations and delusions that occur in PD. Visual hallucinations and illusions are thought to be caused by specific cognitive and higher visual function deficits and patients who develop such symptoms early in the disease course have greater rates of cognitive decline and progression to dementia. To date, no studies have investigated whether such deficits are found prior to the onset of PD psychosis.

Method: Here we compare baseline cognitive, biomarker (structural imaging and cerebrospinal fluid) and other PD psychosis risk factor data in patients who go on to develop illusions or hallucinations within 3-4 years of follow-up in the Parkinson's Progression Markers Initiative cohort of newly diagnosed PD.

Results: Of n=423 patients with PD, n=115 (27%) reported predominantly illusions with the median time of onset at 19.5 months follow-up. At study entry these patients had reduced CSF amyloid Aß1-42, lower olfaction scores, higher depression scores and increased REM sleep behaviour disorder symptoms compared to patients without early onset PD psychosis but no differences in cognitive, higher visual or structural imaging measures. A subset of patients with early onset formed hallucinations (n=21) had reduced higher visual function at baseline, cortical thinning in parietal, occipital and frontal cortex and reduced hippocampal volume.

Conclusions: The findings suggest early onset illusions and formed hallucinations are linked to amyloid pathology in PD and point to a difference in the underlying pathophysiological mechanism of illusions and formed hallucinations, with implications for their respective links to future cognitive decline.

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Figures

Figure 1

Number of PD patients in the PD Psy1+ group at each follow-up assessment. Y axis scaled to total number of patients with PD (n=423).

Figure 2. Global cognition and the onset of PD Psychosis

The MoCA score trajectory prior to onset of PD psychosis (black circle) in subgroups of patients with PD psychosis onset at 1 year (green line), two years (red line) and three years (blue line). The trajectory of patients without PD psychosis (PD-Psy0) is shown in black. The slopes of MoCA decline do not differ between groups with and without PD psychosis (see text for further details).

Figure 3

Cortical thickness differences between patients with formed hallucinations (PDPsy2+) compared to those without PD psychosis (PD-Psy0) on a surface rendered right hemisphere in lateral (left panel) and medial (right panel) view. Colour coding indicates cluster significance on a logarithmic scale of p values (−log10).