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

Abstract 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 timeConclusions: 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 )