Mild Cognitive Impairment in Parkinson's Disease
Mild Cognitive Impairment in Parkinson's Disease
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 pathologies in PD and the individuals at risk of ultimately developing PDD is critical for targeted intervention and drug discovery studies. Further work is required, however, to determine the significance of PD-MCI and also to validate the diagnostic criteria. This would be best delivered in the form of longitudinal studies in homogenous cohorts of PD participants, to allow prognostication and generalisation among the PD population. At the present time, no drug therapies are available for PD-MCI. Management includes screening for the disorder, excluding treatable causes of cognitive decline and cautious use of dopamine agonists and medications such as anticholinergics.
Mild cognitive impairment (MCI) is defined as a transitional state between normality and dementia, with subjective or objective cognitive impairment and little or no impairment in daily functioning. The last 15 years has seen a large rise in the literature on MCI in the general population, with data from epidemiological studies demonstrating that 10–15% per year progress to dementia, largely of the Alzheimer's-type. MCI may represent the earliest clinical spectrum of dementia, and therefore has been identified as an important opportunity to study the underlying pathogenesis of cognitive impairment, possible biomarkers and neuroprotective therapeutic strategies to prevent subsequent cognitive decline. Furthermore, as the prevalence of MCI increases with age, it is an important concept for geriatricians to recognise.
Dementia is a frequent and distressing complication of Parkinson's disease (PD) with a cumulative incidence approaching 80% in community-based studies. Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are both part of a Lewy body (LB) disease spectrum and are separated by the 'one year rule', which states that if extrapyramidal motor features have been present for 12 months or more before the onset of dementia, the diagnosis should be PDD; otherwise it is that of DLB. The development of PDD predicts increased mortality, caregiver strain, institutionalisation and healthcare costs. The concept of MCI in Parkinson's disease (PD-MCI) has received increasing attention recently, with opposing views as to whether it is part of the PDD continuum or a fluid process of changing impairment. Although not analogous to the field of Alzheimer's disease (AD), where the significance of MCI is perhaps better understood, it is now recognised that PD-MCI may represent a pre-dementia state and is associated with increased healthcare costs, poorer self-reported quality of life, greater falls risk plus subtle impairments in instrumental activities of daily living. A recent study demonstrated that the level of global disability, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) Part II and the Schwab and England ADL scale, increased in a stepwise manner from those with PD who were cognitively normal, to those with PD-MCI and finally to those with PDD. An earlier study examining PD participants with a range of cognitive abilities demonstrated a strong association between cognitive impairment and impairment in ADLs, even among non-demented patients. This narrative review therefore concentrates on our current understanding of PD-MCI, including the most recent studies, and its importance for geriatricians caring for patients with PD.
Abstract and Introduction
Abstract
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 pathologies in PD and the individuals at risk of ultimately developing PDD is critical for targeted intervention and drug discovery studies. Further work is required, however, to determine the significance of PD-MCI and also to validate the diagnostic criteria. This would be best delivered in the form of longitudinal studies in homogenous cohorts of PD participants, to allow prognostication and generalisation among the PD population. At the present time, no drug therapies are available for PD-MCI. Management includes screening for the disorder, excluding treatable causes of cognitive decline and cautious use of dopamine agonists and medications such as anticholinergics.
Introduction
Mild cognitive impairment (MCI) is defined as a transitional state between normality and dementia, with subjective or objective cognitive impairment and little or no impairment in daily functioning. The last 15 years has seen a large rise in the literature on MCI in the general population, with data from epidemiological studies demonstrating that 10–15% per year progress to dementia, largely of the Alzheimer's-type. MCI may represent the earliest clinical spectrum of dementia, and therefore has been identified as an important opportunity to study the underlying pathogenesis of cognitive impairment, possible biomarkers and neuroprotective therapeutic strategies to prevent subsequent cognitive decline. Furthermore, as the prevalence of MCI increases with age, it is an important concept for geriatricians to recognise.
Dementia is a frequent and distressing complication of Parkinson's disease (PD) with a cumulative incidence approaching 80% in community-based studies. Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are both part of a Lewy body (LB) disease spectrum and are separated by the 'one year rule', which states that if extrapyramidal motor features have been present for 12 months or more before the onset of dementia, the diagnosis should be PDD; otherwise it is that of DLB. The development of PDD predicts increased mortality, caregiver strain, institutionalisation and healthcare costs. The concept of MCI in Parkinson's disease (PD-MCI) has received increasing attention recently, with opposing views as to whether it is part of the PDD continuum or a fluid process of changing impairment. Although not analogous to the field of Alzheimer's disease (AD), where the significance of MCI is perhaps better understood, it is now recognised that PD-MCI may represent a pre-dementia state and is associated with increased healthcare costs, poorer self-reported quality of life, greater falls risk plus subtle impairments in instrumental activities of daily living. A recent study demonstrated that the level of global disability, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) Part II and the Schwab and England ADL scale, increased in a stepwise manner from those with PD who were cognitively normal, to those with PD-MCI and finally to those with PDD. An earlier study examining PD participants with a range of cognitive abilities demonstrated a strong association between cognitive impairment and impairment in ADLs, even among non-demented patients. This narrative review therefore concentrates on our current understanding of PD-MCI, including the most recent studies, and its importance for geriatricians caring for patients with PD.
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