Cognitive decline in Parkinson disease
Dag Aarsland1,2, Byron Creese1,3, Marios Politis1,4
1KCL-PARCOG group, Institute of Psychiatry, Psychology &Neuroscience, King's College London, De Crespigny Park, London SE5 8AF, UK.
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.
Insights
Mild cognitive impairment (MCI) often precedes dementia in Parkinson disease (PD). While MCI can progress, stabilization or improvement is possible, with cognitive training showing promise.
Area of Science:
- Neuroscience
- Neurology
- Gerontology
Background:
- Dementia is common in advanced Parkinson disease (PD).
- Mild cognitive impairment (MCI) is increasingly studied as a pre-dementia stage in PD.
- The progression of cognitive impairment in PD is variable, with potential for stabilization or reversal.
Purpose of the Study:
- To review the mechanisms and biomarkers associated with cognitive decline in Parkinson disease.
- To explore the predictive value of biomarkers and genetic factors for cognitive impairment in PD.
- To assess current treatment and prevention strategies for cognitive decline in PD.
Main Methods:
- Review of longitudinal studies on cognitive impairment in Parkinson disease.
- Analysis of biomarker studies, including cerebrospinal fluid (CSF) analysis and advanced neuroimaging.
- Examination of genetic risk factors associated with cognitive decline in PD.
Main Results:
- Low CSF amyloid-β42 levels predict cognitive decline and dementia in PD, indicating comorbid Alzheimer disease (AD).
- Genetic factors like APOE*ε4, GBA, and SCNA mutations are linked to cognitive decline in PD.
- Cognitive enhancing medications offer some benefit for PD dementia, but prevention of MCI progression remains unproven.
Conclusions:
- Cognitive impairment in Parkinson disease is multifactorial, involving Lewy pathology, AD-related changes, and genetic predispositions.
- Biomarkers and genetic factors are crucial for predicting cognitive decline in PD.
- While treatments exist for PD dementia, proactive strategies like cognitive training show potential for managing MCI in PD.
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