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Cognitive decline in Parkinson disease
Open accessAbstract
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-β 42, 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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“Moreover there are several candidate genetic risk factors that overlap for AD and PD, most notably APOE and MAPT [127].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [127]
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Bailey, A. S., St‐Onge, E., Madge, V., Shafiee, N., Gagnon, J., Dagher, A., Collins, D. L., & Sharp, M. E. (2026) · medRxiv · doi:10.64898/2026.07.21.26358398
Tao, C., Cui, S., Shen, Y., Cheng, Y., Zhu, J., & Yu, Y. (2026) · iScience · doi:10.1016/j.isci.2026.116903
Aldaihan, M. M., Albalawi, M. S., Aldubayan, H. T., Alderaa, A. A., Almurdi, M. M., & AlAbdulwahab, S. S. (2026) · Neurorehabilitation · doi:10.1177/10538135261470442
Hasani, F., Kherad, M. E., Sarasyabi, M. S., Jazi, K., Ashkbari, A., Ahmadi, P., Heidarpour, H., Masrour, M., Khamaki, S., Rahmati, R., et al. (2026) · Brain and Behavior · doi:10.1002/brb3.71602
Metadata
- Authors
- Aarsland, D., Creese, B., Politis, M., Chaudhuri, K. R., ffytche, D. H., Weintraub, D., & Ballard, C.
- Affiliations
- King's College London (GB)
- Corresponding author
- Aarsland, Dag
- Venue
- Nature Reviews Neurology
- Published
- 2017-03-03
- Volume
- 13
- Issue
- 4
- Pages
- 217-231
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC5643027
- OpenAlex
- W2593272776
- Cited by
- 1,027
- References
- 216
- Citations by year
- 2026: 102 · 2025: 99 · 2024: 138 · 2023: 104 · 2022: 105 · 2021: 171 · 2020: 116 · 2019: 89 · 2018: 68 · 2017: 33
- FWCI
- 11.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Open Research Exeter (University of Exeter) (acceptedVersion)
- Figshare (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- South London and Maudsley NHS Foundation Trust
- National Institute for Health and Care Research
- King's College London
- Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- National Institute of Neurological Disorders and Stroke (P50NS053488)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Parkinson's disease, cognitive decline, Parkinson's disease dementia, mild cognitive impairment, cerebrospinal fluid biomarkers, amyloid-beta 42, Lewy body pathology, APOE ε4, GBA mutations, cognitive training, nootropic drugs
- MeSH terms
- Dementia, Humans, Parkinson Disease, Cognitive Dysfunction
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