Cognitive impairment in Parkinson's disease: A clinical and pathophysiological overview (original) (raw)
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Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment
The Lancet Neurology, 2012
Dementia is one of the most common and important aspects of Parkinson's disease and has consequences for patients and caregivers, and has health-related costs. Mild cognitive impairment is also common and frequently progresses to dementia. The underlying mechanisms of dementia associated with Parkinson's disease are only partly known and no mechanism-based treatments are available. Both dysmetabolism of α-synuclein and amyloid-protein and cholinergic defi cits contribute to cognitive impairment in Parkinson's disease, and preliminary fi ndings show that imaging and neurophysiological and peripheral biomarkers could be useful in diagnosis and prognosis. Rivastigmine is the only licensed treatment for dementia in Parkinson's disease, but emerging evidence suggests that memantine might also be useful. Whether these or other treatments can delay the progression from mild cognitive impairment to dementia in Parkinson's disease is a key research question.
Parkinson’s Disease–Mild Cognitive Impairment (PD-MCI): A Useful Summary of Update Knowledge
Frontiers in Aging Neuroscience, 2019
Mild cognitive impairment (MCI) is a common feature in Parkinson's Disease (PD), even at the time of diagnosis. Some levels of heterogeneity in nature and severity of cognitive impairment and risk of conversion to Parkinson's Disease Dementia (PDD) exist. This brief overview summarized the current understanding of MCI in PD, by considering the following major points: historical development of the clinical entity, evaluation, epidemiology, predictors and outcomes, neuroimaging findings, pathophysiology, treatment, and pharmacological and non-pharmacological intervention. MCI in PD represents a concept in evolution and plays a pivotal role in advancing our understanding of the disease mechanisms, with the ultimate goal of building effective strategies to prevent conversion into PDD. Challenges for future research are also discussed.
Frontiers in Neurology, 2012
Parkinson's disease (PD) is a common, disabling, neurodegenerative disorder. In addition to classical motor symptoms, non-motor features are now widely accepted as part of the clinical picture, and cognitive decline is a very important aspect of the disease, as it brings an additional significant burden for the patient and caregivers. The diagnosis of cognitive decline in PD, namely mild cognitive impairment (MCI) and dementia, can be extremely challenging, remaining largely based on clinical and cognitive assessments. Diagnostic criteria and methods for PD dementia and MCI have been recently issued by expert work groups. This manuscript has synthesized relevant data in order to obtain a pragmatic and updated review regarding cognitive decline in PD, from milder stages to dementia. This text will summarize clinical features, diagnostic methodology, and therapeutic issues of clinical decline in PD. Relevant clinical genetic issues, including recent advances, will also be approached.
While Parkinson's disease (PD) traditionally has been defined by its characteristic motor hallmarks, non-motor features such as cognitive impairment and dementia are increasingly recognized as part of PD. Mild cognitive impairment is common in non-demented PD patients, occurring in about 20-50%. Frequency estimates and clinical features of mild cognitive impairment in PD (PD-MCI), however, vary across studies due to methodological differences and lack of uniform diagnostic criteria for PD-MCI. Overall, PD-MCI patients exhibit nonamnestic deficits in cognitive domains such as executive function, attention, and visuospatial function; however, the cognitive phenotype of PD-MCI is heterogeneous with some patients demonstrating greater amnestic deficits. PD-MCI patients, particularly those with posterior cortical profiles, may be at high risk for developing dementia. Various biomarkers studied in PD-MCI including cerebrospinal fluid, genetic analyses, and neuroimaging suggest that there may be distinct PD-MCI profiles. Future studies using uniform PD-MCI diagnostic criteria and incorporating biomarkers and longitudinal follow-up of PD-MCI cohorts are needed to understand PD-MCI as a transitional state between normal cognition and dementia.
Mild cognitive impairment in Parkinson's disease
Age and Ageing, 2013
The concept of mild cognitive impairment (MCI) in the general population has received increased attention over recent years, and is associated with risk of progression to Alzheimer's disease. Within Parkinson's disease (PD), MCI (PD-MCI) is also now recognised to be relatively common, with certain subtypes predicting progression to Parkinson's disease dementia (PDD). Recently, criteria to better characterise PD-MCI and its subtypes have been produced by the Movement Disorder Society. In contrast to the population as a whole, where amnestic MCI is the most common subtype, non-amnestic PD-MCI dominates, with prominent executive and attention dysfunction. Although the pathophysiology of PD-MCI is poorly understood and encompasses both PD and non-PD pathology, it is most likely the result of a complex interaction between neurotransmitter dysfunction, synaptic pathology, protein aggregation and neuronal damage. Determining the factors that influence the progression of these p...
The neurobiological basis of cognitive impairment in Parkinson's disease
Movement Disorders, 2014
The recent formalization of clinical criteria for PD with dementia (PD-D) codifies many studies on this topic, including those assessing biological correlates. These studies show that the emergence of PD-D occurs on the background of severe dopamine deficits with the main pathological drivers of cognitive decline being a synergistic effect between α-synuclein and Alzheimer's disease pathology. The presence of these pathologies correlates with a marked loss of limbic and cortically projecting dopamine, noradrenaline, serotonin and acetylcholine neurons, although the exact timing of these relationships remains to be determined. Genetic factors, such as triplications in the α-synuclein gene, lead to a clear increased risk of PD-D, while others, such as parkin mutations, are associated with a reduced risk of PD-D. The very recent formalization of clinical criteria for PD with mild cognitive impairment (PD-MCI) allows only speculation on its biological and genetic bases. Critical assessment of animal models shows that chronic low dose MPTP treatment in primates recapitulates PD-MCI over time, enhancing the current biological concept of PD-MCI as having enhanced dopamine deficiency in frontostriatal pathways as well as involvement of other neurotransmitter systems. Data from other animal models support multiple transmitter involvement in cognitive impairment in PD. While dopamine dysfunction has been highlighted because of its obvious role in PD, the role of the other neurotransmitter systems, neurodegenerative pathologies and genetic factors in PD-MCI remain to be fully elucidated.
Cognitive impairment in nondemented Parkinson's disease
Movement Disorders, 2011
A substantial percentage of patients with newly diagnosed Parkinson's disease without dementia are reported to be affected by cognitive impairment (CI). In practice, however, CI is underrecognized, as the signs may not be apparent in early-stage disease and many routine assessment tools lack the sensitivity to detect subtle cognitive dysfunction. Patients with PD and mild CI (MCI) may have a higher risk of developing dementia than cognitively intact PD patients; however, it is not currently known which patients with CI are at increased risk of developing dementia. This review summarizes current knowledge about CI in nondemented PD; it discusses the structural and functional changes associated with CI and addresses areas of unmet needs. We focus on questions that should be addressed in future studies to achieve consensus on its characteristics and definition, pathophysiology, epidemiology, diagnosis and assessment, and treatment and management.
The Lancet Neurology, 2010
Cognitive impairment in patients with Parkinson's disease is gaining increased clinical signifi cance owing to the relative success of therapeutic approaches to the motor symptoms of this disorder. Early investigations contributed to the concept of subcortical dementia associated with bradyphrenia and cognitive rigidity. For cognition in parkinsonian disorders, this notion developed into the concept of mild cognitive impairment and fronto-executive dysfunction in particular, driven mainly by dopaminergic dysmodulation and manifesting as defi cits in fl exibility, planning, working memory, and reinforcement learning. However, patients with Parkinson's disease could also develop a syndrome of dementia that might depend on non-dopaminergic, cholinergic cortical dysfunction. Recent fi ndings, supplemented by advances in neuroimaging and genetic research, reveal substantial heterogeneity in the range of cognitive defi cits in patients with Parkinson's disease. Remediation and management prospects for these cognitive defi cits are based on neuropharmacological and cognitive rehabilitation approaches.
Cognitive decline in Parkinson’s disease: the complex picture
npj Parkinson's Disease, 2016
Mild cognitive impairment (PD-MCI) and dementia (PDD) are among the most frequent non-motor symptoms in Parkinson's disease (PD). PD-MCI is six times more likely than age-matched controls to develop dementia and the PDD prevalence is 80% after 15-20 years of disease. Therefore, research has focused on the identification of early dementia biomarkers including specific cognitive at-risk profiles hoping to implement therapeutic interventions when they are most likely to be efficacious. However, given the heterogeneous neuropathological, neurochemical, and neuropsychological nature of cognitive deficits, definition of a comprehensive cognitive model of PDD is a challenge. Evidence from neuroimaging studies using different methods and techniques suggests that in addition to degeneration of the dopaminergic system, other mechanisms have a role including β-amyloid and tau deposition, and that specific cognitive scales could help identifying a malignant profile. Prospective studies combining neuroimaging techniques and specific cognitive tests are required to define the interplay between the various neurodegenerative processes and the contribution of structural disconnection in brain functional networks, heralding the development of dementia in PD.