Age-Related Association Between APOE ɛ4 and Cognitive Progression in de novo Parkinson’s Disease

Liu, Jia-Yao; Ma, Lingzhi; Wang, Jun; Cui, Xin-Jing; Sheng, Ze-Hu; Fu, Yan; Li, Meng; Ou, Ya‐Nan; Yu, Jin‐Tai; Tan, Lan; Liang, Yan

doi:10.3233/jad-220976

Cited by 8 publications

(4 citation statements)

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“…APOE ε4 has been identified as a major risk factor for cognitive progression in PD [ 113 ]. It has an age-dependent effect on decline in global cognition as well as in most cognitive domains [ 114 , 115 ]. Carriers of APOE ε4 and GBA mutations had faster cognitive decline and were at higher risk of progression to dementia [ 116 ], whereas no significant gene-related effects were observed for MAPT and SNCA rs356219 [ 117 ].…”

Section: Genetic Factors Of Pd-cimentioning

confidence: 99%

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Jellinger

2023

IJMS

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Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions. Modern neuroimaging studies revealed multilocular cortical and subcortical atrophies and alterations in intrinsic neuronal connectivities. The decreased functional connectivity (FC) of the default mode network (DMN) in the bilateral prefrontal cortex is affected already before the development of clinical CI and in the absence of structural changes. Longitudinal cognitive decline is associated with frontostriatal and limbic affections, white matter microlesions and changes between multiple functional neuronal networks, including thalamo-insular, frontoparietal and attention networks, the cholinergic forebrain and the noradrenergic system. Superimposed Alzheimer-related (and other concomitant) pathologies due to interactions between α-synuclein, tau-protein and β-amyloid contribute to dementia pathogenesis in both PD and dementia with Lewy bodies (DLB). To further elucidate the interaction of the pathomechanisms responsible for CI in PD, well-designed longitudinal clinico-pathological studies are warranted that are supported by fluid and sophisticated imaging biomarkers as a basis for better early diagnosis and future disease-modifying therapies.

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Section: Genetic Factors Of Pd-cimentioning

confidence: 99%

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Jellinger

2023

IJMS

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“…Other studies have suggested a connection between APOE expression and PD [85], and that APOE4 allele increases the risk of motor deficiency and decreases the age of PD onset [86][87][88]. It was suggested that PD patients carrying the APOE3/APOE4 and APOE4/APOE4 genotype have greater risk of dementia [89][90][91]. It was previously reported that expression of APOE4 in α-Syn transgenic mice exacerbates pathology, as shown by increased α-Syn aggregation, neuronal and synaptic loss, and impaired behavioral performances [92,93].…”

Section: Rab39bmentioning

confidence: 99%

Autophagy in Parkinson’s Disease

Nechushtai,

Frenkel,

Pinkas-Kramarski

2023

Biomolecules

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Parkinson’s disease (PD) is a devastating disease associated with accumulation of α-synuclein (α-Syn) within dopaminergic neurons, leading to neuronal death. PD is characterized by both motor and non-motor clinical symptoms. Several studies indicate that autophagy, an important intracellular degradation pathway, may be involved in different neurodegenerative diseases including PD. The autophagic process mediates the degradation of protein aggregates, damaged and unneeded proteins, and organelles, allowing their clearance, and thereby maintaining cell homeostasis. Impaired autophagy may cause the accumulation of abnormal proteins. Incomplete or impaired autophagy may explain the neurotoxic accumulation of protein aggregates in several neurodegenerative diseases including PD. Indeed, studies have suggested the contribution of impaired autophagy to α-Syn accumulation, the death of dopaminergic neurons, and neuroinflammation. In this review, we summarize the recent literature on the involvement of autophagy in PD pathogenesis.

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“…The APOE ε4 allele is a significant genetic risk factor for sporadic Alzheimer's disease (AD) and dementia with Lewy bodies 2,3 . Several studies have reported an association between APOE ε4 status and cognitive impairment in individuals with PD, indicating its potential role as a genetic risk factor for the development of cognitive decline in these patients 4–6 . Moreover, recent studies have suggested that APOE ε4 may also influence motor symptom progression in PD 7 .…”

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confidence: 99%

“…2,3 Several studies have reported an association between APOE ε4 status and cognitive impairment in individuals with PD, indicating its potential role as a genetic risk factor for the development of cognitive decline in these patients. [4][5][6] Moreover, recent studies have suggested that APOE ε4 may also influence motor symptom progression in PD. 7 Given the potential influence of APOE ε4 on cognition and other nonmotor/motor symptoms in PD, this study aims to investigate the associations between APOE ε4 genotypes and motor/nonmotor symptoms in a large sample of patients.…”

mentioning

confidence: 99%

Associations of Apolipoprotein ε4 Genotypes with Motor and Nonmotor Symptoms in Parkinson's Disease: A Cross‐Sectional Study

Kapan

Haider

Wakolbinger

et al. 2023

Movement Disord Clin Pract

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BACKGROUNDApolipoprotein ε4 (APOE ε4) has been associated with cognitive decline in Parkinson's disease (PD), but little is known about its relationship with motor and other non‐motor symptoms, and whether APOE ε4 retains an influence on cognition when other factors are considered.OBJECTIVETo investigate the impact of APOE ε4 on motor/non‐motor symptoms and its relationship with other factors affecting cognition in individuals with PD.METHODSWe analysed data from 7,616 individuals, comparing motor/non‐motor symptoms in different APOE genotypes using binary logistic regression. Multivariate logistic regression examined factors associated with cognitive impairments, including APOE ε4, Geriatric Depression Scale (GDS), Non‐motor Symptom Questionnaire (NMS), MDS‐UPDRS Part II, and physical activity level.RESULTSAPOE ε4 heterozygosity was modestly associated with lower cognitive scores (OR=0.92, 95% CI: 0.87‐0.99), while no significant association was found for any other non‐motor and motor symptoms. However, in multivariate analysis, cognitive impairment was associated with higher GDS (OR 1.28, 95% CI 1.23‐1.34), NMS (OR 1.22, 95% CI 1.19‐1.25), and MDS‐UPDRS Part II (OR 1.07, 95% CI 1.06‐1.09) scores, whereas physical activity was negatively associated (OR 0.99, 95% CI 0.98‐0.99). APOE ε4 was no longer significant after adjusting for these factors.CONCLUSIONSThere is a link between cognition and APOE ε4 in PD patients; however, when considering multiple factors, APOE ε4 plays a subordinate role. Other factors, such as depression, physical activity, and other non‐motor symptoms, demonstrate a stronger influence on cognitive impairment.This article is protected by copyright. All rights reserved.

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Age-Related Association Between APOE ɛ4 and Cognitive Progression in de novo Parkinson’s Disease

Cited by 8 publications

References 42 publications

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Autophagy in Parkinson’s Disease

Associations of Apolipoprotein ε4 Genotypes with Motor and Nonmotor Symptoms in Parkinson's Disease: A Cross‐Sectional Study

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