Parkinsonism and dementia

Koros, Christos; Stefanis, Leonidas; Scarmeas, Nikolaos

doi:10.1016/j.jns.2021.120015

Cited by 16 publications

(19 citation statements)

References 166 publications

(228 reference statements)

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“…The degree of cognitive deterioration in PD is variable and ranges from mild cognitive impairment to dementia. There is also variation in the number and type of affected cognitive domains which can involve either a single domain like executive or visuospatial function or multiple ones (Koros et al., 2022 ). Cognitive disorder is general even in the early stages of PD (Foltynie et al., 2004 ), and nearly 80% of patients with mild cognitive impairment eventually develop dementia later in the disease (Caviness et al., 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of repetitive transcranial magnetic stimulation on gait disorders and cognitive dysfunction in Parkinson's disease: A systematic review with meta‐analysis

et al. 2022

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Background Repetitive transcranial magnetic stimulation (rTMS) is acknowledged to be crucial to manage freezing of gait (FOG) and cognitive impairment for patients with Parkinson's disease (PD), but its effectiveness is unclear. Objective To determine the effects of rTMS on FOG and cognitive function in people with PD and to investigate potential factors that modulate the rTMS effects. Methods Databases searched included PubMed, Web of Science, EMBASE, and the Cochrane Library from inception to December 31, 2021. Eligible studies include a controlled randomized clinical trial of rTMS intervention for FOG and cognitive dysfunction in PD patients. The weighted mean difference (WMD) with 95% confidence intervals (CI) were calculated with fixed‐effects models. The outcome of the study included gait and cognitive assessments. Results Sixteen studies with a total of 419 patients were included. Fixed‐effects analysis revealed that rTMS was effective in improving freezing of gait questionnaire scores (short‐term effect: WMD = −0.925, 95% CI: −1.642 to −0.209, p = .011; long‐term effect: WMD = −2.120, 95% CI: −2.751 to −1.489, p = .000), 10‐m walking time (short‐term effect: WMD = −0.456, 95% CI: −0.793 to −0.119, p = .008; long‐term effect: WMD = −0.526, 95% CI: −0.885 to −0.167, p = .004), Timed Up‐and‐Go scores (short‐term effect: WMD = −1.064, 95% CI: −1.555 to −0.572, p = .000; long‐term effect: WMD = −1.097, 95% CI: −1.422 to −0.772, p = .000), Montreal cognitive assessment (WMD = 3.714, 95% CI: 2.567 to 4.861, p = .000), and frontal assessment battery (WMD = −0.584, 95% CI: −0.934 to −0.234, p = .001). Conclusions RTMS showed a beneficial effect on FOG and cognitive dysfunction in parkinsonism. However, the optimal rTMS protocol has not been determined and further high‐quality studies are needed.

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Section: Introductionmentioning

confidence: 99%

Effects of repetitive transcranial magnetic stimulation on gait disorders and cognitive dysfunction in Parkinson's disease: A systematic review with meta‐analysis

et al. 2022

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“…Cognitive dysfunction in genetic forms of PD is variable, depending on the affected gene, the particular mutation, but also on other factors such as additional genetic modifiers, lifestyle, co-morbidities and environmental components. There is marked heterogeneity in the expressivity of the dementia phenotype between different genetic forms of PD and even among members of the same family 12 . Patients harboring mutations in the genes Alpha-synuclein ( SNCA ) and GBA1 often have a more pronounced cognitive burden than those with mutations in Parkin (PRKN) or Leucine-rich repeat kinase 2 (LRRK2) 12,13 .…”

Section: Introductionmentioning

confidence: 99%

“…There is marked heterogeneity in the expressivity of the dementia phenotype between different genetic forms of PD and even among members of the same family 12 . Patients harboring mutations in the genes Alpha-synuclein ( SNCA ) and GBA1 often have a more pronounced cognitive burden than those with mutations in Parkin (PRKN) or Leucine-rich repeat kinase 2 (LRRK2) 12,13 . The putative role of APOE as a genetic modifier of cognitive trajectories in genetic forms of PD is largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Impact ofAPOEgenotype on cognition in idiopathic and genetic forms of Parkinson’s disease

Koros

Brockman

Simitsi

et al. 2022

Preprint

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Background: Apolipoprotein E (APOE) genotype may be associated with the development of cognitive decline in idiopathic Parkinson's disease i(PD), however its effect in genetic PD is understudied. Objectives: In the current work we aimed to assess the impact of APOE genotype on cognition in iPD as well as in genetic PD with mutations in the Alpha-synuclein (SNCA) and Glycocerebrosidase (GBA1) genes. Methods: Two independent PD cohorts were analyzed: The first cohort (Athens) included 50 iPD patients, 35 patients with the p.A53T SNCA mutation and 59 patients with GBA1 mutations (13 mild /46 severe). The second cohort (Tuebingen) included 292 patients with GBA1 mutations (170 risk/ 52 mild/ 70 severe). All patients underwent cognitive testing and were genotyped for APOE. Results: In the iPD subgroup, carriers of at least one APOE exhibited lower Montreal Cognitive Assessment test (MoCA) score as compared to non-carriers (p=0.044). Notably, in the p.A53T SNCA subgroup, APOE carriers also had lower MoCA scores compared to non-carriers (p=0.039). There were no APOE-related differences in the two GBA1 subgroups (Athens, p=0.729; Tuebingen p=0.585). Conclusions: We confirm the impact of APOE on cognitive decline in iPD and for the first time report a similar effect in p.A53T SNCA mutation carriers, who represent the prototypical genetic synucleinopathy. Contrary, the lack of such an effect in two independent cohorts of GBA1 mutation carriers, who are thought to also manifest a predominant alpha-synuclein-driven cognitive decline, suggests differences in factors associated with cognitive dysfunction between different genetic forms of synucleinopathies.

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“…1 The putative role of APOE as a genetic modifier of cognitive trajectories in genetic forms of Parkinson's disease (PD) is largely unexplored. 2 We have analyzed two independent PD cohorts. The first cohort (Athens) included 50 iPD patients, 35 patients with the p.A53T α-synuclein (SNCA) mutation and 59 patients with glucocerebrosidase (GBA1) mutations (13 mild/46 severe).…”

Section: Impact Of Apoe Genotype On Cognition In Idiopathic and Genet...mentioning

confidence: 99%

Impact of APOE Genotype on Cognition in Idiopathic and Genetic Forms of Parkinson's Disease

et al. 2023

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Parkinsonism and dementia

Cited by 16 publications

References 166 publications

Effects of repetitive transcranial magnetic stimulation on gait disorders and cognitive dysfunction in Parkinson's disease: A systematic review with meta‐analysis

Effects of repetitive transcranial magnetic stimulation on gait disorders and cognitive dysfunction in Parkinson's disease: A systematic review with meta‐analysis

Impact ofAPOEgenotype on cognition in idiopathic and genetic forms of Parkinson’s disease

Impact of APOE Genotype on Cognition in Idiopathic and Genetic Forms of Parkinson's Disease

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