Background: Alzheimer's disease (AD) is the most common cause of dementia in older patients. Rivastigmine (RV, Exelon, Novartis), a reversible cholinesterase inhibitor, improves clinical manifestations of AD and may enhance ACh-modulated electroencephalogram (EEG) alpha frequency. This pilot study aimed to determine the effects of two formulations of RV [transdermal patch (RV-TDP) and oral capsules (TV-CP)] on alpha frequency, in particular the posterior dominant rhythm, and cognitive function [assessed by the Mini-Mental State Examination (MMSE)] in patients with AD.
Methods: Subjects with AD were assigned to receive either RV-TDP 10 cm(2) or RV-CP 12 mg/day. All patients underwent EEG recordings at the beginning and end of the 18-month study period using P3, P4, O1, and O2 electrodes, each at high (10.5-13.0 Hz) and low (8.0-10.5 Hz) frequency. MMSE scores were determined at the start of the study (T0) and at three successive 6-month intervals (T1, T2, and T3).
Results: RV-TDP administration (n = 10) maintained cognitive function as evidenced by stable MMSE scores from baseline to 18 months (21.07 ± 2.4-21.2 ± 3.1) compared with a decrease in MMSE score with RV-CP (n = 10) over 18 months [18.3 ± 3.6-13.6 ± 5.06 (adjusted for covariates p = 0.006)]. MMSE scores were significantly different between treatment groups from 6 months (p = 0.04). RV-TDP also increased the spectral power of alpha waves in the posterior region measured with electrode P3 in a significantly great percentage of patients than TV-CP from baseline to 18 months; 80% vs 30%, respectively [p = 0.025 (χ (2) test)].
Conclusions: RV-TDP was associated with a greater proportion of patients with increased posterior region alpha wave spectral power and significantly higher cognitive function at 18 months, compared with RV-CP treatment. Our findings suggest that RV-TDP provides an effective long-term management option in patients with AD compared with oral RV-CP. This study is a pilot, open-label study with a clear explorative purpose and with a small number of patients. Further randomized, double-blind, placebo-controlled trial studies with a bigger sample size as well as healthy controls are needed to support these initial results.
Keywords: Alzheimer’s disease; EEG; cognitive function; dementia; transdermal rivastigmine oral rivastigmine.