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Cognitive decline in Parkinson disease

Nature Reviews Neurology volume 13, pages 217–231 (2017)Cite this article

Subjects

Key Points

  • The full spectrum of cognitive impairment, from subjective cognitive decline to dementia, has been observed in Parkinson disease (PD)

  • Mild cognitive impairment in PD usually progresses to dementia, but can be stable and even revert in some patients

  • The aetiology of cognitive impairment in PD has not been fully elucidated, but limbic and cortical Lewy body pathology seems to be the main cause

  • Amyloid plaque pathology also contributes to cognitive decline in PD, and amyloid pathology detected by cerebrospinal fluid analysis and imaging can predict subsequent dementia

  • Other probable mechanisms include genetics, synaptic pathology, neurotransmitter changes and inflammation

  • Cholinesterase inhibitors have symptomatic effects, but no disease-modifying treatments are available to reduce the risk of dementia in PD

Abstract

Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition — or even reversal to normal cognition — is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

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Figure 1: Amyloid-β PET scans in Parkinson disease dementia.
Figure 2: Overview of risk factors for Parkinson disease dementia.

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Acknowledgements

The authors thank Dr Michael Haworth for help in preparing the final manuscript. The authors would like to thank the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. D.A. is a Royal Society Wolfson Research Merit Award Holder and would like to thank the Wolfson Foundation and the Royal Society for their support. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

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Authors and Affiliations

  1. KCL-PARCOG group, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK

    Dag Aarsland, Byron Creese, Marios Politis, K. Ray Chaudhuri, Dominic H. ffytche, Daniel Weintraub & Clive Ballard

  2. Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK

    Dag Aarsland & Dominic H. ffytche

  3. University of Exeter Medical School, University of Exeter, Exeter, EX1 2LU, UK

    Byron Creese & Clive Ballard

  4. Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK

    Marios Politis

  5. Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, National Parkinson Foundation Centre of Excellence, King's College London/Kings College Hospital, 5 Cutcombe Road, London, SE5 9RT, UK

    K. Ray Chaudhuri

  6. Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, 3615 Chestnut Street, #330, Philadelphia, 19104, Pennsylvania, USA

    Daniel Weintraub

  7. Parkinson's Disease and Mental Illness Research, Education and Clinical Centres (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Centre, 3900 Woodland Avenue, Philadelphia, 19104, Pennsylvania, USA

    Daniel Weintraub

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All authors contributed equally to all aspects of manuscript preparation.

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Correspondence to Dag Aarsland.

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Competing interests

D.A. has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals and GE Health, and serves as a paid consultant for H. Lundbeck and Axovant. K.R.C. has consulted and served on advisory boards for Britannia, AbbVie, Neuronova, Mundipharma and UCB, and has also served on advisory boards for Synapsus and Medtronic. He has received honoraria from Boehringer Ingelheim, GlaxoSmithKline, AbbVie, Britannia, UCB, Mundipharma, Otsuka and Zambon, and grants from Boehringer Ingelheim, GlaxoSmithKline, Britannia, AbbVie, UCB and Neuronova. He holds intellectual property rights for the KPP scale and the PDSS, and receives royalties for the books Non-Motor Symptoms of Parkinson's Disease and Fastfacts: Parkinson's Disease. C.B. declares grants and personal fees from Lundbeck and Acadia, and personal fees from Roche, Orion, GlaxoSmithKline, Otusaka, Heptares and Lilly. The other authors declare no competing interests.

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Aarsland, D., Creese, B., Politis, M. et al. Cognitive decline in Parkinson disease. Nat Rev Neurol 13, 217–231 (2017). https://doi.org/10.1038/nrneurol.2017.27

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