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Use of Cholinesterase Inhibitors in Non-Alzheimer’s Dementias

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Abstract

Non-Alzheimer’s dementias constitute 30% of all dementias and present with major cognitive and behavioral disturbances. Cholinesterase inhibitors improve memory by increasing brain acetylcholine levels and are approved symptomatic therapies for Alzheimer’s disease (AD). They have also been investigated in other types of dementias with potential cholinergic dysfunction. There is compelling evidence for a profound cholinergic deficit in Lewy Body dementia (LBD) and Parkinson’s disease dementia (PDD), even to a greater extent than AD. However, this deficit is difficult to objectivize in vascular dementia (VaD) given the increased comorbidity with AD. Furthermore, there is minimal to no evidence for cholinergic loss in frontotemporal dementia (FTD). Although cholinesterase inhibitors showed significant improvement in cognitive, behavioral, and functional measures in both LBD and PDD clinical trials, only rivastigmine is approved for PDD, due to the heterogeneity of the scales used, the duration of trials, and the limited sample sizes impacting data interpretation. Similarly, the interpretation of findings in VaD trials are limited by the lack of pre-defined inclusion criteria for ‘pure VaD’ and the wide heterogeneity of patients enrolled with respect to location and extent of cerebrovascular disease. In FTD patients, cholinesterase inhibitors were mostly associated with worsening of cognitive and behavioral symptoms. In non-AD dementias, cholinesterase inhibitors were well tolerated, with increased reports of mild to moderate cholinergic side effects and a non-significant trend for increased cardio and cerebrovascular events with rivastigmine in VaD, justifying their cautious use on a case-by-case basis, especially when there is evidence for cholinergic deficit.

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Authors and Affiliations

  1. Department of Psychiatry, American University of Beirut, Beirut, Lebanon

    Paul Noufi

  2. Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, 1438 S Grand Blvd, St. Louis, MO, 63104, USA

    Rita Khoury, Sajeeka Jeyakumar & George T. Grossberg

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  1. Paul Noufi
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  2. Rita Khoury
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  3. Sajeeka Jeyakumar
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  4. George T. Grossberg
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Correspondence to Rita Khoury.

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Authors PN, RK, and SJ declare that they have no conflict of interest. Author GG is a consultant for Acadia, Alkahest, Allergen, Avanir, Axovant, Bioxcel, GE, Genentech, Lundbeck, Novartis, Otsuka, Roche, and Takeda; received research support from Janssen, NIA, and Roche; is on the safety monitoring committee for EryDel, Merck and Newron; and is on the Speaker’s Bureau for Acadia.

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Noufi, P., Khoury, R., Jeyakumar, S. et al. Use of Cholinesterase Inhibitors in Non-Alzheimer’s Dementias. Drugs Aging 36, 719–731 (2019). https://doi.org/10.1007/s40266-019-00685-6

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