Systematic review of genetic variants associated with cognitive impairment and depressive symptoms in Parkinson’s disease

AbstractObjective:Cognitive impairment and depression are among the most prevalent and most disabling non-motor symptoms in Parkinson’s disease (PD). The genetic factors that are associated with these symptoms remain uncertain. This systematic review aims to summarise the prevailing evidence from all genetic association studies investigating the genetic variants associated with cognitive impairment and depressive symptoms in people with PD.Method:A systematic review using five online databases: PubMed, PsycINFO, CINAHL, EMBASE and OpenGrey (PROSPERO protocol: CRD42017067431). We completed the quality assessment using the Q-Genie tool.Results:2353 articles were screened, and 43 articles were found to be eligible to be included. A meta-analysis of studies investigating LRRK2 rs34637584 confirmed that the minor allele carriers had significantly less cognitive impairment (p = 0.015). Further meta-analyses showed that GBA variants rs76763715 (p < 0.001) and rs421016 (p = 0.001) were significantly associated with more cognitive impairment in people with PD. Minor alleles of GBA variants rs76763715, rs421016, rs387906315 and rs80356773 were associated with more depressive symptoms in PD. Moreover, APOE ε4 allele has been associated with more cognitive impairment in PD. BDNF (rs6265) and CRY1 (rs2287161) variants have been associated with more depressive symptoms in people with PD.Conclusions:PD carriers of GBA variants are at high risk for cognitive decline and depression. Screening for these variants may facilitate early identification and effective management of these non-motor symptoms. The molecular mechanisms underlying favourable cognitive functioning in LRRK2 rs34637584 variant carriers warrant further investigation.

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Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson’s disease in Upper Egypt: case-control study

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00341-0 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Hamdy N. El-Tallawy ◽

Tahia H. Saleem ◽

Wafaa M. Farghaly ◽

Heba Mohamed Saad Eldien ◽

Ashraf Khodaery ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Case Control Study ◽

Case Control ◽

Control Group ◽

Motor Symptoms ◽

And Control ◽

Non Motor Symptoms ◽

Control Study

Abstract Background Parkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients. Results In a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8. Conclusion Genetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.

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Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson’s Disease: A Longitudinal Analysis of Two International Cohorts

Journal of Parkinson s Disease ◽

10.3233/jpd-212570 ◽

2021 ◽

pp. 1-11

Author(s):

Valentina Leta ◽

Daniele Urso ◽

Lucia Batzu ◽

Daniel Weintraub ◽

Nataliya Titova ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

De Novo ◽

Motor Dysfunction ◽

Group Differences ◽

Motor Symptoms ◽

Kaplan Meier ◽

Patients At Risk ◽

Non Motor Symptoms

Background: Constipation is regarded as one of the prodromal features of Parkinson’s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson’s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p < 0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p < 0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

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The association of cognitive impairment and other non-motor symptoms among Thai Parkinson's disease patients

Journal of the Neurological Sciences ◽

10.1016/j.jns.2021.119607 ◽

2021 ◽

Vol 429 ◽

pp. 119607

Author(s):

Chayasak Wantaneeyawong ◽

Kittithatch Booncharoen ◽

Kanokwan Wattana ◽

Orawan Ronran ◽

Siwahdol Chaimano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Motor Symptoms ◽

Non Motor Symptoms

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Non-motor symptoms are associated with REM sleep behavior disorder in Parkinson’s disease: a systematic review and meta-analysis

Neurological Sciences ◽

10.1007/s10072-020-04769-9 ◽

2020 ◽

Author(s):

Dan Xie ◽

Qiuyan Shen ◽

Junying Zhou ◽

Yanming Xu

Keyword(s):

Systematic Review ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rem Sleep ◽

Meta Analysis ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Motor Symptoms ◽

Sleep Behavior ◽

Non Motor Symptoms

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P112: Reporting of non-motor symptoms and cognitive impairment in Parkinson's disease clinic attenders

European Geriatric Medicine ◽

10.1016/s1878-7649(14)70287-6 ◽

2014 ◽

Vol 5 ◽

pp. S118

Author(s):

K. Nagaratnam ◽

A. Monkhouse ◽

H. Jones ◽

S. Wheeler ◽

J. Beal ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Motor Symptoms ◽

Disease Clinic ◽

Non Motor Symptoms

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Brasilia Parkinson Cohort: assessing clinical, neuropsychological and imaging predictors of cognitive decline in Parkinson's disease

10.7287/peerj.preprints.27639v1 ◽

2019 ◽

Author(s):

Pedro Renato de Paula Brandão ◽

Fernando Bisinoto Maluf ◽

Talyta Grippe ◽

Ingrid Faber ◽

Danilo Assis Pereira ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Diffusion Tensor ◽

Motor Symptoms ◽

Imaging Data ◽

Diagnostic And Statistical Manual ◽

Nested Case Control ◽

Non Motor Symptoms

The following study protocol describes the rationale and methods of a cohort with a nested case-control study, which aims to identify risk factors and predictors of cognitive dysfunction in Parkinson's disease (PD). It is a study that will follow PD every 18 months with a comprehensive neuropsychological, clinical (motor and non-motor symptoms) and imaging (Magnetic Resonance Imaging) data collection. The criteria for diagnosing mild cognitive impairment (MCI) and dementia will respect the parameters previously published by the International Working Group on Mild Cognitive Impairment, and compared with those recommended by the Fifth edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-5) and the International Parkinson's and Movement Disorders Society (MDS) criteria. We will also evaluate the neural substrate and underpinnings of PD non-motor symptoms, using advanced neuroimaging techniques, such as diffusion tensor imaging (DTI) and gray matter and white matter volumetric measurements.

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Brasilia Parkinson Cohort: assessing clinical, neuropsychological and imaging predictors of cognitive decline in Parkinson's disease

10.7287/peerj.preprints.27639 ◽

2019 ◽

Author(s):

Pedro Renato de Paula Brandão ◽

Fernando Bisinoto Maluf ◽

Talyta Grippe ◽

Ingrid Faber ◽

Danilo Assis Pereira ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Diffusion Tensor ◽

Motor Symptoms ◽

Imaging Data ◽

Diagnostic And Statistical Manual ◽

Nested Case Control ◽

Non Motor Symptoms

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The correlation of non-motor symptoms and sleep on balance in Parkinson’s disease patients with normal cognition and mild cognitive impairment

Irish Journal of Medical Science (1971 -) ◽

10.1007/s11845-020-02462-6 ◽

2021 ◽

Author(s):

Mevhibe Saricaoglu ◽

Nesrin Helvaci Yilmaz ◽

Fahriye Feriha Ozer ◽

Lutfu Hanoglu

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Motor Symptoms ◽

Non Motor Symptoms ◽

Normal Cognition

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Effectiveness of Telerehabilitation on Motor Impairments, Non-motor Symptoms and Compliance in Patients With Parkinson's Disease: A Systematic Review

Frontiers in Neurology ◽

10.3389/fneur.2021.627999 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chiara Vellata ◽

Stefano Belli ◽

Francesca Balsamo ◽

Andrea Giordano ◽

Roberto Colombo ◽

...

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Patient Satisfaction ◽

Cochrane Library ◽

Clinical Aspects ◽

Motor Symptoms ◽

Non Motor Symptoms

Introduction: Parkinson's disease (PD) is a chronic neurodegenerative disease involving a progressive alteration of the motor and non-motor function. PD influences the patient's daily living and reduces participation and quality of life in all phases of the disease. Early physical exercise can mitigate the effects of symptoms but access to specialist care is difficult. With current technological progress, telemedicine, and telerehabilitation is now a viable option for managing patients, although few studies have investigated the use of telerehabilitation in PD. In this systematic review, was investigated whether telerehabilitation leads to improvements in global or specific motor tasks (gait and balance, hand function) and non-motor dysfunction (motor speech disorder, dysphagia). The impact of TR on quality of life and patient satisfaction, were also assessed. The usage of telerehabilitation technologies in the management of cognitive impairment was not addressed.Method: An electronic database search was performed using the following databases: PubMed/MEDLINE, COCHRANE Library, PEDro, and SCOPUS for data published between January 2005 and December 2019 on the effects of telerehabilitation systems in managing motor and non-motor symptoms. This systematic review was conducted in accordance with the PRISMA guideline and was registered in the PROSPERO database (CRD42020141300).Results: A total of 15 articles involving 421 patients affected by PD were analyzed. The articles were divided into two categories based on their topic of interest or outcome. The first category consisted of the effects of telerehabilitation on gait and balance (3), dexterity of the upper limbs (3), and bradykinesia (0); the second category regarded non-motor symptoms such as speech disorders (8) and dysphagia (0). Quality of life (7) and patient satisfaction (8) following telerehabilitation programs were also analyzed, as well as feasibility and costs.Conclusion: Telerehabilitation is feasible in people affected by PD. Our analysis of the available data highlighted that telerehabilitation systems are effective in maintaining and/or improving some clinical and non-clinical aspects of PD (balance and gait, speech and voice, quality of life, patient satisfaction).Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier: CRD42020141300.

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