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Mild cognitive impairment: an update in Parkinson's disease and lessons learned from Alzheimer's disease.

ABSTRACT: Cognitive dysfunction is an important focus of research in Parkinson's disease (PD) and Alzheimer's disease (AD). While the concept of amnestic mild cognitive impairment (MCI) as a prodrome to AD has been recognized for many years, the construct of MCI in PD is a relative newcomer with recent development of diagnostic criteria, biomarker research programs and treatment trials. Controversies and challenges, however, regarding PD-MCI's definition, application, heterogeneity and different trajectories have arisen. This review will highlight current research advances and challenges in PD-MCI. Furthermore, lessons from the AD field, which has witnessed an evolution in MCI/AD definitions, relevant advances in biomarker research and development of disease-modifying and targeted therapeutic trials will be discussed.

SUBMITTER: Goldman JG

PROVIDER: S-EPMC4968199 | biostudies-other | 2015 Oct

REPOSITORIES: biostudies-other

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Mild cognitive impairment: an update in Parkinson's disease and lessons learned from Alzheimer's disease.

Goldman Jennifer G JG Aggarwal Neelum T NT Schroeder Cynthia D CD

Neurodegenerative disease management 20151030 5

Cognitive dysfunction is an important focus of research in Parkinson's disease (PD) and Alzheimer's disease (AD). While the concept of amnestic mild cognitive impairment (MCI) as a prodrome to AD has been recognized for many years, the construct of MCI in PD is a relative newcomer with recent development of diagnostic criteria, biomarker research programs and treatment trials. Controversies and challenges, however, regarding PD-MCI's definition, application, heterogeneity and different trajector ...[more]

PMID: 26517759

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Project description:BackgroundThere is increasing interest in therapeutic ketosis as a potential therapy for neurodegenerative disorders-in particular, mild cognitive impairment (MCI), Alzheimer's disease (AD), and Parkinson's disease (PD)-following a proof-of-concept study in Parkinson's disease published in 2005.MethodsTo provide an objective assessment of emerging clinical evidence and targeted recommendations for future research, we reviewed clinical trials involving ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease reported since 2005. Levels of clinical evidence were systematically reviewed using the American Academy of Neurology criteria for rating therapeutic trials.Results10 AD, 3 MCI, and 5 PD therapeutic ketogenic trials were identified. Respective grades of clinical evidence were objectively assessed using the American Academy of Neurology criteria for rating therapeutic trials. We found class "B" evidence (probably effective) for cognitive improvement in subjects with mild cognitive impairment and subjects with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele (APOε4-). We found class "U" evidence (unproven) for cognitive stabilization in individuals with mild-to-moderate Alzheimer's disease positive for the apolipoprotein ε4 allele (APOε4+). We found class "C" evidence (possibly effective) for improvement of non-motor features and class "U" evidence (unproven) for motor features in individuals with Parkinson's disease. The number of trials in Parkinson's disease is very small with best evidence that acute supplementation holds promise for improving exercise endurance.ConclusionsLimitations of the literature to date include the range of ketogenic interventions currently assessed in the literature (i.e., primarily diet or medium-chain triglyceride interventions), with fewer studies using more potent formulations (e.g., exogenous ketone esters). Collectively, the strongest evidence to date exists for cognitive improvement in individuals with mild cognitive impairment and in individuals with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele. Larger-scale, pivotal trials are justified in these populations. Further research is required to optimize the utilization of ketogenic interventions in differing clinical contexts and to better characterize the response to therapeutic ketosis in patients who are positive for the apolipoprotein ε4 allele, as modified interventions may be necessary.

Dataset Information

Mild cognitive impairment: an update in Parkinson's disease and lessons learned from Alzheimer's disease.

Publications

Mild cognitive impairment: an update in Parkinson's disease and lessons learned from Alzheimer's disease.

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