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The morbid anatomy of dementia in Parkinson’s disease

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Abstract

Dementia in Parkinson’s disease (PD/PDD) is a common complication with a prevalence of up to 50%, but the specific changes underlying the cognitive decline remain undefined. Neuronal degeneration resulting in the dysfunction of multiple subcortical neurochemical projection systems has been described along with Lewy body-type pathology in cortical and limbic regions. Advanced alpha-synuclein (αSyn) pathology is not necessarily sufficient for producing dementia and concomitant Alzheimer’s disease (AD) change has also been proposed as a possible substrate of PDD. A lack of consensus in the extant literature likely stems from clinical heterogeneity and variable reliability in clinical characterisation as well as other historical and methodological issues. The concurrent presence of abnormally deposited αSyn, amyloid-β and tau proteins in the PDD brain and the interaction of these molecules in a linked pathological cascade of AD and PD-related mechanisms may prove important in determining the underlying pathological process for the development of dementia in PD and this concept of combined pathologies awaits further investigation.

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Acknowledgments

The authors would like to thank the UK Parkinson’s Disease Society, registered charity 948776, for their continual support. The valuable comments of Professor Manuel Graeber and Dr Stephen Gentleman are also greatly appreciated. The present work was funded through a grant from the UK Parkinson’s Disease Society (G-0709).

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  1. Neuropathology Unit, Division of Neuroscience and Mental Health, Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, Charing Cross Campus, Fulham Palace Road, London, W6 8RF, UK

    Michail E. Kalaitzakis & Ronald K. B. Pearce

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  1. Michail E. Kalaitzakis
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Correspondence to Michail E. Kalaitzakis.

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Kalaitzakis, M.E., Pearce, R.K.B. The morbid anatomy of dementia in Parkinson’s disease. Acta Neuropathol 118, 587–598 (2009). https://doi.org/10.1007/s00401-009-0597-x

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  • DOI: https://doi.org/10.1007/s00401-009-0597-x

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