APOE,MAPT, andSNCAGenes and Cognitive Performance in Parkinson Disease

Mata, Ignacio; Leverenz, James B.; Weintraub, Daniel; Trojanowski, John Q.; Hurtig, Howard I.; Deerlin, Vivianna M. Van; Ritz, Beate; Rausch, Rebecca; Rhodes, Shannon; Factor, Stewart A.; Wood-Siverio, Cathy; Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie; Espay, Alberto J.; Revilla, Fredy J.; Devoto, Johnna; Hu, Shu Ching; Cholerton, Brenna; Wan, Jia; Montine, Thomas J.; Edwards, Karen L.; Zabetian, Cyrus P.

doi:10.1001/jamaneurol.2014.1455

Cited by 183 publications

(196 citation statements)

References 45 publications

(47 reference statements)

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“…The disease mechanisms underlying cognitive impairment and dementia in Parkinson's disease are an unclear mix of intrinsic processes related to regional accumulation of a-synuclein (encoded by SNCA) and loss of nigrostriatal and midbrain dopaminergic neurons, and processes of Alzheimer's disease, characterized by regional accumulation of amyloid-b and pathologic tau species. Psychometric testing has demonstrated impairment in varying domains in patients with Parkinson's disease, with some demonstrating an amnestic pattern Mata et al, 2014) and others impairment in executive and/or visuospatial function. Multiple pathophysiologic processes converge to cause known deficits in lateral frontoparietal networks that support attention and task control, as evidenced by metabolic covariance analysis (Eckert et al, 2007;Huang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Group comparison of spatiotemporal dynamics of intrinsic networks in Parkinson’s disease

Madhyastha

Askren

Zhang

et al. 2015

Brain

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Section: Introductionmentioning

confidence: 99%

Group comparison of spatiotemporal dynamics of intrinsic networks in Parkinson’s disease

Madhyastha

Askren

Zhang

et al. 2015

Brain

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“…18 The importance of APOE was further underscored by the finding that the APOE e4 variant was associated with poorer cognitive performance in a study of more than 1,000 patients with PD across multiple centers. 19 Interestingly, the authors noted that the MAPT H1 haplotype, while associated with overall PD risk, did not predict cognitive performance in this dataset. Other recent studies have been mixed with respect to association of the MAPT H1 haplotype and rate of cognitive decline in PD.…”

mentioning

confidence: 70%

Parkinson disease and cognitive impairment

Davis

Racette

2016

Neur Clin Pract

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Purpose of review: While the distinctive motor symptoms of Parkinson disease (PD) have been described for centuries, cognitive impairment has only recently been recognized as a central feature. Studies have yielded clues to the etiology and natural history of cognitive impairment in PD, but much remains unclear and effective therapies are needed. Recent findings: Longitudinal cohort studies demonstrate that almost all patients with PD will develop dementia if they live long enough. New CSF biomarker and genetic studies suggest that it may soon be possible to forecast and track the progression of dementia in PD. Sleep and sleep disturbance appear to be intrinsically linked with PD, although the implications for individual outcomes and opportunities for intervention are unclear. Multidisciplinary treatment approaches incorporating cognitive training may help to improve outcomes. Summary: We review several recent advances in understanding the pathophysiology, genetics, and management of cognitive impairment in PD. Neurol Clin Pract 2016;6:452-458 C ognitive impairment is a disabling comorbidity for many patients with Parkinson disease (PD) and represents a major challenge for physicians, caregivers, and the health care system.Prevalence and natural history of PD dementia: Near-universal prevalence and progression Clinical features of cognitive impairment in PD involve a wide range of cognitive domains, including executive function, visuospatial reasoning, memory, and language function, and can include additional features including visual hallucinations, paranoia, and fluctuations in attention.1 PD is often marked primarily by visuospatial and executive deficits, in contrast to Alzheimer disease (AD), where memory impairment predominates. Cognitive impairment in PD encompasses a spectrum of severity from relatively mild symptoms to end-stage

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“…alzgene.org/). Besides AD and CVD, genetic studies have also connected APOE and its ε2/ε3/ε4 alleles to multiple physiological conditions and disorders, including aging (18,19), diabetes (20), dysbetalipoproteinemia (21), frontotemporal dementia (22), fragile X-associated ataxia (23), glomerulopathy (24), Lewy body dementia (25), metabolic syndrome (26), retinal-related disorders (27) disease (28), posttraumatic stress disorder (29), primary progressive aphasia (30), schizophrenia (31), stroke (32), traumatic brain injury (33), and vascular dementia (34).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic considerations of the APOE gene

Foraker

2015

Biomolecular Concepts

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Abstract:The apolipoprotein E (APOE) gene is robustly linked with numerous physiological conditions, including healthy aging, altered cardiovascular fitness, and cognitive function. These connections have been established primarily by phenotype-genotype association studies using APOE's three common genetic variants (ε2, ε3, and ε4). These variants encode for the three apoE protein isoforms (E2, E3, and E4), which have slightly different structures and, consequently, distinct functions in lipid metabolism. However, the differential lipid binding and transferring properties of these isoforms cannot fully explain the association of APOE with such a wide range of physiological phenotypes. One potential explanation for APOE's pleiotropic roles may lie in its unique epigenetic properties. In this article, we present a brief review of the APOE gene and protein, its disease associations, and epigenetic components, with a focus on DNA methylation. We close with a discussion of the prospective epigenetic implications of APOE in disease.

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APOE,MAPT, andSNCAGenes and Cognitive Performance in Parkinson Disease

Cited by 183 publications

References 45 publications

Group comparison of spatiotemporal dynamics of intrinsic networks in Parkinson’s disease

Group comparison of spatiotemporal dynamics of intrinsic networks in Parkinson’s disease

Parkinson disease and cognitive impairment

Epigenetic considerations of the APOE gene

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