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


METHODS
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.
KCL-PARCOG Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Dominic H
DH
Ffytche
Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
Joana B
JB
Pereira
KCL-PARCOG Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|University of Exeter Medical School, University of Exeter, Exeter, Devon, UK.
Clive
C
Ballard
KCL-PARCOG Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
K Ray
KR
Chaudhuri
KCL-PARCOG Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Parkinson's Disease and Mental Illness Research, Education and Clinical Centres (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Centre, Philadelphia, Pennsylvania, USA.
Daniel
D
Weintraub
KCL-PARCOG Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Centre of Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
Dag
D
Aarsland
D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D003702:Delusions / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D003704:Dementia / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006212:Hallucinations / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011618:Psychotic Disorders / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)