The effect of anticholinergic drugs on cognition of patients with Parkinson’s disease: a cohort study from the Egyptian population

ABSTRACT

Background

Cognitive dysfunction is a non-motor manifestation of Parkinson’s disease (PD). We aimed to determine the frequency and patterns of cognitive dysfunction in treated patients with PD and their predictors.

Research design and methods

This study included 80 patients (male = 48; female = 32) and 30 healthy individuals. They underwent neuropsychiatric evaluations. Measurements included Beck’s depression inventory – II (BDI-II), mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA).

Results

Patients had mean age of 55.56 ± 9.06 yrs, duration of PD of 4.86 ± 2.71 yrs and Hoehn and Yahr Scoring of 2.19 ± 0.89. They were on levodopa/carbidopa therapy and adjuvant therapy with benztropine mesylate, an anticholinergic drug, (n = 51) or amantadine sulfate, a dopaminergic drug, (n = 29). Sixteen (20%) had moderate depressive symptoms. Mild and moderate cognitive impairments were reported in 38.8% and 28.8% (by MMSE) and 46.3% and 31.3% (by MoCA). Patients had lower global cognitive scoring (p = 0.0001) and scorings of different cognitive functions (naming, attention, language, abstraction, memory and orientation) than controls. Patients treated with benztropine had lower cognition than with amantadine. Correlation analyses showed that lower cognition was only associated with chronic PD and its treatment (p = 0.0001).

Conclusions

Cognitive dysfunction is common with PD (77.5%) particularly with anticholinergic drugs. De-prescription of anticholinergics is recommended for patients with PD.

KEYWORDS:

• Parkinson’s disease
• cognition
• acetylcholine
• anticholinergic medications
• benztropine mesylate
• amantadine sulfate

Abbreviations

PD; Parkinson’s disease; MCI; mild cognitive impairment; SNpc, substantia nigra pars compacta; VTA, ventral tegmental area; NAc, nucleus accumbens; GPe, globus pallidus externa; GPi, globus pallidus interna; STN, subthalamic nucleus; GABA, gamma amino butyric acid; BFCC, Basal Forebrain Cholinergic Corticopetal; nBM, nucleus basalis of Meynert; MSN, medial septal nucleus; PPN, pedunculopontine neurons; LDT, lateral dorsal tegmental; SChIs, striatal cholinergic interneurons; MAO-B; monoamine oxidase B; COMT; catechol-O-methyl transferase; AChEIs; acetyl cholinesterase inhibitors, NMDA; N-Acetyl-D-Aspartate; BDI-II, Beck’s Depression Inventory – II; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethics statement

The protocol of the study was in accordance with the revised Helsinki Declaration (2013) and was approved by the medical research ethics committees of the Faculty of Medicine, Assiut University, Assiut, Egypt. (ID#: AU-FM_Neuro0063_2022).Patients provided written informed consent for participation.

Author contributions

All authors have substantially contributed to the conception and design of the article and interpreting the relevant literature and been involved in writing the article and revised it for intellectual contents. SA Hamed drafted the manuscript and drew Figure 1. AF El Hadad substantially and critically reviewed the article. All authors have agreed on the journal to which the article was submitted. All authors have reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage. All authors agreed to take responsibility and be accountable for the contents of the article and to share responsibility to resolve any questions raised about the accuracy or integrity of the published work.

Additional information

Funding

This paper was not funded.