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. 2024 Feb 9:39:100870.
doi: 10.1016/j.lanepe.2024.100870. eCollection 2024 Apr.

The impact of psychiatric comorbidity on Parkinson's disease outcomes: a systematic review and meta-analysis

Ella Burchill  1 , Cameron James Watson  2   3 , Jack B Fanshawe  4   5 , James Brunton Badenoch  6 , Emma Rengasamy  7 , Dory Anthony Ghanem  8 , Constantine Holle  8 , Isabella Conti  2 , Mohammed Ahmed Sadeq  9 , Aman Saini  8 , Abdelilah Lahmar  10 , Ben Cross  11 , Gareth McGuigan  12 , Amar Nandrha  8 , Edward J Kane  3 , Julia Wozniak  8 , Reem Mohamed Farouk Ghorab  9 , Jia Song  13 , Andrew Sommerlad  1   13 , Andrew Lees  14 , Michael S Zandi  14 , Anthony S David  1   15 , Glyn Lewis  1 , Ben Carter  16 , Jonathan P Rogers  1
Affiliations

The impact of psychiatric comorbidity on Parkinson's disease outcomes: a systematic review and meta-analysis

Ella Burchill et al. Lancet Reg Health Eur. .

Abstract

Background: The burden of psychiatric symptoms in Parkinson's disease includes depression, anxiety, apathy, psychosis, and impulse control disorders. However, the relationship between psychiatric comorbidities and subsequent prognosis and neurological outcomes is not yet well understood. In this systematic review and meta-analysis, in individuals with Parkinson's disease, we aimed to characterise the association between specific psychiatric comorbidities and subsequent prognosis and neurological outcomes: cognitive impairment, death, disability, disease progression, falls or fractures and care home admission.

Methods: We searched MEDLINE, Embase, PsycINFO and AMED up to 13th November 2023 for longitudinal observational studies which measured disease outcomes in people with Parkinson's disease, with and without specific psychiatric comorbidities, and a minimum of two authors extracted summary data. Studies of individuals with other parkinsonian conditions and those with outcome measures that had high overlap with psychiatric symptoms were excluded to ensure face validity. For each exposure-outcome pair, a random-effects meta-analysis was conducted based on standardised mean difference, using adjusted effect sizes-where available-in preference to unadjusted effect sizes. Study quality was assessed using the Newcastle-Ottawa Scale. Between-study heterogeneity was assessed using the I2 statistic and publication bias was assessed using funnel plots. PROSPERO Study registration number: CRD42022373072.

Findings: There were 55 eligible studies for inclusion in meta-analysis (n = 165,828). Data on participants' sex was available for 164,514, of whom 99,182 (60.3%) were male and 65,460 (39.7%) female. Study quality was mostly high (84%). Significant positive associations were found between psychosis and cognitive impairment (standardised mean difference [SMD] 0.44, [95% confidence interval [CI] 0.23-0.66], I2 30.9), psychosis and disease progression (SMD 0.46, [95% CI 0.12-0.80], I2 70.3%), depression and cognitive impairment (SMD 0.37 [95% CI 0.10-0.65], I2 27.1%), depression and disease progression (SMD 0.46 [95% CI 0.18-0.74], I2 52.2), depression and disability (SMD 0.42 [95% CI 0.25-0.60], I2 7.9%), and apathy and cognitive impairment (SMD 0.60 [95% CI 0.02-1.19], I2 27.9%). Between-study heterogeneity was moderately high.

Interpretation: Psychosis, depression, and apathy in Parkinson's disease are all associated with at least one adverse outcome, including cognitive impairment, disease progression and disability. Whether this relationship is causal is not clear, but the mechanisms underlying these associations require exploration. Clinicians should consider these psychiatric comorbidities to be markers of a poorer prognosis in people with Parkinson's disease. Future studies should investigate the underlying mechanisms and which treatments for these comorbidities may affect Parkinson's disease outcomes.

Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at University College London Hospitals NHS Foundation Trust, National Brain Appeal.

Keywords: Depression; Meta-analysis; Neuropsychiatry; Parkinson's disease; Psychosis; Systematic review.

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Conflict of interest statement

JPR reports research funding from the Wellcome Trust, royalties from Taylor & Francis, payment for reviewing from Johns Hopkins University Press and speaker fees from the Alberta Psychiatric Association and Infomed Research & Training Ltd. A Lees reports consultancies from Britannia Pharmaceuticals and BIAL Portela. He also reports grants and/or research support from the Frances and Renee Hock Fund, and honoraria from Britannia Pharmaceuticals, BIAL and Convatec. MSZ declares honoraria for one lecture each for each of the three mentioned in the last 3 years: Norwegian Neurological Society; Copenhagen Neuropsychological Society, Rigshospitalet; and Cygnet Healthcare. A Sommerlad reports research grants from the Wellcome Trust, Alzheimer's Association and Brain Canada. CW reports grant funding, including support for attending meetings and travel, from the NIHR Academic Clinical Fellowship. GL reports funding from the Wellcome Trust, NIHR, UK Research Institute (UKRI). He also reports funding support for attending meetings and/or travel from ECNP 2023, participation on NIHR trial TSC and holds a leadership role on the NIHR doctoral training fellowship panel. All other authors declare no conflict of interests. The funders had no role in the writing of the manuscript or the decision to submit it for publication. The authors have not been paid to write this article by a pharmaceutical company or other agency. Authors were not precluded from accessing data in the study and they accept responsibility to submit for publication.

Figures

Fig. 1
Fig. 1
PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources.
Fig. 2
Fig. 2
The association of psychosis with Parkinson's disease outcomes.
Fig. 3
Fig. 3
The association of depression with Parkinson's disease outcomes.
Fig. 4
Fig. 4
The association of apathy with Parkinson's disease outcomes.
Fig. 5
Fig. 5
The association of anxiety with Parkinson's disease outcomes.
Fig. 6
Fig. 6
The association of ICBs with Parkinson's disease outcomes.
Fig. 7
Fig. 7
A heatmap of the association of psychiatric exposures with Parkinson's disease outcomes.
See this image and copyright information in PMC

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