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

Ella Burchill; Cameron James Watson; Jack B Fanshawe; James Brunton Badenoch; Emma Rengasamy; Dory Anthony Ghanem; Constantine Holle; Isabella Conti; Mohammed Ahmed Sadeq; Aman Saini; Abdelilah Lahmar; Ben Cross; Gareth McGuigan; Amar Nandrha; Edward J Kane; Julia Wozniak; Reem Mohamed Farouk Ghorab; Jia Song; Andrew Sommerlad; Andrew Lees; Michael S Zandi; Anthony S David; Glyn Lewis; Ben Carter; Jonathan P Rogers

doi:10.1016/j.lanepe.2024.100870

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

Lancet Reg Health Eur. 2024 Feb 9:39:100870. doi: 10.1016/j.lanepe.2024.100870. eCollection 2024 Apr.

Authors

Ella Burchill¹, Cameron James Watson^{2

3}, Jack B Fanshawe^{4

5}, James Brunton Badenoch⁶, Emma Rengasamy⁷, Dory Anthony Ghanem⁸, Constantine Holle⁸, Isabella Conti², Mohammed Ahmed Sadeq⁹, Aman Saini⁸, Abdelilah Lahmar¹⁰, Ben Cross¹¹, Gareth McGuigan¹², Amar Nandrha⁸, Edward J Kane³, Julia Wozniak⁸, Reem Mohamed Farouk Ghorab⁹, Jia Song¹³, Andrew Sommerlad^{1

13}, Andrew Lees¹⁴, Michael S Zandi¹⁴, Anthony S David^{1

15}, Glyn Lewis¹, Ben Carter¹⁶, Jonathan P Rogers¹

Affiliations

¹ Division of Psychiatry, University College London, London, UK.
² Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
³ South London and Maudsley NHS Foundation Trust, UK.
⁴ Department of Psychiatry, University of Oxford, Oxford, UK.
⁵ Oxford Health NHS Foundation Trust, Oxford, UK.
⁶ Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁷ Department of Public Health and Primary Care, University of Cambridge, UK.
⁸ Medical School, University College London, London, UK.
⁹ Faculty of Medicine, Misr University for Science and Technology, 6th of October City, Egypt.
¹⁰ Faculty of Medicine, Mohamed First University, Oujda, Morocco.
¹¹ Mersey Care NHS Foundation Trust, Liverpool, UK.
¹² Ayrshire & Arran NHS Foundation Trust, Scotland, UK.
¹³ Camden and Islington NHS Foundation Trust, London, UK.
¹⁴ UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
¹⁵ UCL Institute of Mental Health, University College London, London, UK.
¹⁶ Department of Biostatistics and Health Informatics, King's College London, London, UK.

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.

Abstract

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