Efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by Parkinson’s disease without dementia: a systematic review
Background Parkinson’s disease (PD) is primarily characterised by parkinsonism due to nigro-striatal dopaminergic denervation. While therapeutic strategies have traditionally focused on compensating for dopaminergic deficit, growing evidence reveals an involvement of cholinergic and glutamatergic pa...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-08-01
|
| Series: | BMJ Neurology Open |
| Online Access: | https://neurologyopen.bmj.com/content/7/2/e001079.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849249613192626176 |
|---|---|
| author | Pietro Cortelli Maria Guarino Giovanna Calandra-Buonaura Giulia Giannini Pietro Guaraldi Francesco Nonino Ilaria Cani Nicola Grotteschi Luca Baldelli Monia Donati Maria Domenica Camerlingo Luisa Sambati |
| author_facet | Pietro Cortelli Maria Guarino Giovanna Calandra-Buonaura Giulia Giannini Pietro Guaraldi Francesco Nonino Ilaria Cani Nicola Grotteschi Luca Baldelli Monia Donati Maria Domenica Camerlingo Luisa Sambati |
| author_sort | Pietro Cortelli |
| collection | DOAJ |
| description | Background Parkinson’s disease (PD) is primarily characterised by parkinsonism due to nigro-striatal dopaminergic denervation. While therapeutic strategies have traditionally focused on compensating for dopaminergic deficit, growing evidence reveals an involvement of cholinergic and glutamatergic pathways in the pathogenesis of the motor and non-motor manifestations of the disease. The purpose of this review is to provide an overview of the efficacy of cholinesterase inhibitors (ChIs) and memantine (glutamate receptor antagonist) in patients affected by PD without dementia on motor (gait, balance) and non-motor (cognitive, behavioural, sleep and autonomic) symptoms usually poorly responsive to levodopa.Methods A systematic review of randomised controlled trials (RCTs) was conducted. The search was performed on PubMed, Cochrane Library and Embase databases for articles published between January 1996 and October 2024, using predefined inclusion and exclusion criteria. Risk of bias was assessed with the Cochrane Risk of Bias tool. Results are presented narratively.Results 12 RCTs were included in this review, with 10 (774 patients) focusing on ChIs and 2 (65 patients) on memantine. Some studies highlighted the beneficial effects of ChI on mild cognitive impairment and suggested potential improvements in apathy and gait disturbances. However, the findings regarding the impact of ChI and memantine on other non-motor symptoms were inconsistent.Conclusions Available RCTs suggest that ChIs may have a valuable role in managing cognitive impairment, apathy and gait disorders in PD patients without dementia. However, due to the lack of strong evidence, a cautious and individualised approach is advisable when considering these treatments.Cite Now |
| format | Article |
| id | doaj-art-38161c080ea64eecb519414ff65cf3e6 |
| institution | Kabale University |
| issn | 2632-6140 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Neurology Open |
| spelling | doaj-art-38161c080ea64eecb519414ff65cf3e62025-08-20T03:57:31ZengBMJ Publishing GroupBMJ Neurology Open2632-61402025-08-017210.1136/bmjno-2025-001079Efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by Parkinson’s disease without dementia: a systematic reviewPietro Cortelli0Maria Guarino1Giovanna Calandra-Buonaura2Giulia Giannini3Pietro Guaraldi4Francesco Nonino5Ilaria Cani6Nicola Grotteschi7Luca Baldelli8Monia Donati9Maria Domenica Camerlingo10Luisa Sambati11Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum, University of Bologna, Bologna, ItalyU.O.C. Clinica Neurologica Rete Metropolitana (NeuroMet), IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, ItalyDepartment of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum, University of Bologna, Bologna, Italy2IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, ItalyCochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Review Group, IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyU.O.C. Clinica Neurologica Rete Metropolitana (NeuroMet), IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum Università di Bologna, Bologna, ItalyU.O.C. Clinica Neurologica Rete Metropolitana (NeuroMet), IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum Università di Bologna, Bologna, ItalyAgenzia Sanitaria e Sociale Regionale Regione Emilia-Romagna, Bologna, ItalyU.O.C. Clinica Neurologica Rete Metropolitana (NeuroMet), IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyBackground Parkinson’s disease (PD) is primarily characterised by parkinsonism due to nigro-striatal dopaminergic denervation. While therapeutic strategies have traditionally focused on compensating for dopaminergic deficit, growing evidence reveals an involvement of cholinergic and glutamatergic pathways in the pathogenesis of the motor and non-motor manifestations of the disease. The purpose of this review is to provide an overview of the efficacy of cholinesterase inhibitors (ChIs) and memantine (glutamate receptor antagonist) in patients affected by PD without dementia on motor (gait, balance) and non-motor (cognitive, behavioural, sleep and autonomic) symptoms usually poorly responsive to levodopa.Methods A systematic review of randomised controlled trials (RCTs) was conducted. The search was performed on PubMed, Cochrane Library and Embase databases for articles published between January 1996 and October 2024, using predefined inclusion and exclusion criteria. Risk of bias was assessed with the Cochrane Risk of Bias tool. Results are presented narratively.Results 12 RCTs were included in this review, with 10 (774 patients) focusing on ChIs and 2 (65 patients) on memantine. Some studies highlighted the beneficial effects of ChI on mild cognitive impairment and suggested potential improvements in apathy and gait disturbances. However, the findings regarding the impact of ChI and memantine on other non-motor symptoms were inconsistent.Conclusions Available RCTs suggest that ChIs may have a valuable role in managing cognitive impairment, apathy and gait disorders in PD patients without dementia. However, due to the lack of strong evidence, a cautious and individualised approach is advisable when considering these treatments.Cite Nowhttps://neurologyopen.bmj.com/content/7/2/e001079.full |
| spellingShingle | Pietro Cortelli Maria Guarino Giovanna Calandra-Buonaura Giulia Giannini Pietro Guaraldi Francesco Nonino Ilaria Cani Nicola Grotteschi Luca Baldelli Monia Donati Maria Domenica Camerlingo Luisa Sambati Efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by Parkinson’s disease without dementia: a systematic review BMJ Neurology Open |
| title | Efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by Parkinson’s disease without dementia: a systematic review |
| title_full | Efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by Parkinson’s disease without dementia: a systematic review |
| title_fullStr | Efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by Parkinson’s disease without dementia: a systematic review |
| title_full_unstemmed | Efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by Parkinson’s disease without dementia: a systematic review |
| title_short | Efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by Parkinson’s disease without dementia: a systematic review |
| title_sort | efficacy of cholinesterase inhibitors and memantine on symptoms not responsive to levodopa in patients affected by parkinson s disease without dementia a systematic review |
| url | https://neurologyopen.bmj.com/content/7/2/e001079.full |
| work_keys_str_mv | AT pietrocortelli efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT mariaguarino efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT giovannacalandrabuonaura efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT giuliagiannini efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT pietroguaraldi efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT francescononino efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT ilariacani efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT nicolagrotteschi efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT lucabaldelli efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT moniadonati efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT mariadomenicacamerlingo efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview AT luisasambati efficacyofcholinesteraseinhibitorsandmemantineonsymptomsnotresponsivetolevodopainpatientsaffectedbyparkinsonsdiseasewithoutdementiaasystematicreview |