Amantadine improves executive and memory functions in patients with parkinsons disease: Double blind parallel two-arm randomized controlled trial

Introduction: Amantadine improves motor symptoms in patients with Parkinson disease (PD) as monotherapy or adjuvant therapy. However data on specific cognitive functions are lacking. Objective: To investigate the effect of amantadine on PD cognition using a wide battery of different domain-specific cognitive abilities. Method: Mild cognitive impaired 35 PD patients (mean HY: 2),with amantadine 400 mg/day twice a day orally as monotherapy (Group A) and 35 PD patients without amantadine (levodopa + rivastigminetreatment Group B)were randomly enrolled in the study. The data collected for each patient included: (1) MMSE, (2) Addenbrook, (3) verbal learning and memory (Hopkins Verbal Learning Test Revised immediate total recall across trials and delayed recall trial), (4) auditory working memory (Letter Number Sequencing subtest from the Wechsler Adult Intelligence Scale – III), (5) processing speed (Digit Symbol subtest from the Wechsler Adult Intelligence Scale-Revised), (6) visuospatial working memory/switching (Trail Making Test, Part B), (7) semantic verbal fluency (animals), (8) phonemic verbal fluency (letters F-A-S or C-F-L), (9) visuospatial functioning (Brief Visuospatial Memory Test—Revised), 10)Depression (15 item Geriatric Depression scale). Results: The cognitive function improved progressively in 6 and 12-month treatment interval as shown by significant improvement on verbal short term (p < 0.001) and auditory working memory (p < 0.001) and visual working memory (p < 0.001) in Group A compared to Group B. Even after controlling for age, education, depression, disease duration, there are persistent differences in the above cognitive tests between the two groups over the time Conclusions: Amantadine alone significantly improves the verbal, auditory memory and visualspatial processing in PD patients. this study is a part as a secondary analysis of a previously prospectively registered clinical trial (the primary trial registration information is ClinicalTrials.gov identifier NCT number NCT04448340) https://clinicaltrials.gov/study/NCT04448340 )