Chathuri Yatawara,1 Fatin Zahra Zailan,1 Esther Vanessa Chua,1 Linda Lay Hoon Lim,1 Eveline Silva,1 Joanna Sihan Wang,1 Adeline Ng,1 Kok Pin Ng,1 Nagaendran Kandiah1 3

1Department of Neurology, National Neuroscience Institute, Singapore, Singapore; 2Duke-NUS Medical School, Singapore, Singapore; 3Lee Kong Chian School of Medicine-Imperial College London, Nanyang Technological University, Singapore, Singapore

Correspondence: Nagaendran KandiahNational Neuroscience Institute, Level 3, Clinical Staff Office, 11 Jalan Tan Tock Seng, Singapore, 308433, SingaporeTel +65 6357 7171Fax +65 6357 7137Email Nagaendran.Kandiah@singhealth.com.sg

Background: Rivastigmine is used to treat cognitive impairment in Alzheimers disease (AD); however, the efficacy of Rivastigmine in patients with AD and concomitant small vessel cerebrovascular disease (svCVD) remains unclear. We investigated the effectiveness of Rivastigmine Patch in patients with AD and svCVD.Methods: In this open-label study, 100 patients with AD and MRI confirmed svCVD received 9.5mg/24 hours Rivastigmine transdermal treatment for 24 weeks. The primary outcome was global cognition indexed using the ADAS-Cog. Secondary outcomes included clinical-rated impression of change (indexed using (ADCSCGIC), activities of daily living (indexed using ADCS-ADL) and side effects.Results: Overall, performance on the ADAS-Cog after 24 weeks deteriorated by 1.78 (SD = 5.29) points. Fifty-two percent of the sample demonstrated improvement or remained stable, while 48% demonstrated worsening of ADAS-Cog scores. Of the 52%, significant improvement (2 or more-point decline) on the ADAS-Cog was observed in 25% of the sample, with a mean change of 5.08 (SD = 3.11). A decline on the ADAS-Cog was observed in 48% of the sample, with a mean change of 6 (SD = 2.98) points. Cognitive outcome did not interact with severity of svCVD. ADCS-ADL scores remained stable from baseline to week 24 and ADCSCGIC reports indicated that 81% of the patients remained stable after treatment. Side effects were reported by 16% of the patients, with contact dermatitis being the most common.Conclusion: Our findings suggest that Rivastigmine may have a role in the management of patients having AD and concomitant mild-severe svCVD, with minimal side effects.

Keywords: rivastigmine, Alzheimers disease, small vessel cerebrovascular disease, treatment

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