Prolonged therapy of dementia with Lewy bodies with quaternary ammonium anti‐muscarinic/high‐dose cholinesterase inhibitor (QAAM/HDCI)

Abstract

AbstractBackgroundDementia with Lewy Bodies (DLB) is the second most common human neurodegenerative disease and the most reduction in CNS choline acetyl‐transferase. This case series demonstrates beneficial effects from a level inhibition of cholinesterase inhibition that can only be achieved with concurrent peripheral muscarinic blockade.MethodPatients were selected from those seen in a single geriatric consultation clinic after 2010. DLB was diagnosed by the Consensus criteria of the third report (2005) or fourth (2017) of the DLB consortium by a geriatrician, with concurring neurologist in most cases. Patients received rivastigmine at doses greater that the upper limit of FDA approved dosing. Does greater than 12 mg oral, or 13.3 mg transdermal were paired with glycopyrrolate 1‐4 mg orally twice daily. Concurrent use of carbidopa/levodopa, selegiline was permitted but use of dopamine receptor agonists other than low dose quetiapine, other acetyl‐cholinesterase inhibitors or centrally acting anti‐muscarinic agents was not. Criteria for selection included treatment more than one year, the ability to perform a Mini Mental State Examination (MMSE) at the time of initiation and the availability of follow up data. The MMSE was performed in a standardized format. Functional Assessment Stage (FAST) was determined by nurse and physician after an interview with patient and caregivers.ResultMMSE values over time were compared to recently published rates of decline of DLB. All patients had MMSE and functional improvement, with most having a reduction in the rate of decline of MMSE scores.ConclusionThe results show that prolonged symptomatic, cognitive and functional improvement of dementia with Lewy Bodies is possible with the high‐level inhibition of central nervous system cholinesterase achievable when rivastigmine is combined with glycopyrrolate. The discussion correlates these observations with current experimental, clinical and epidemiological evidence regarding the mechanism and treatment of this, and other, neurodegenerative diseases.