Game changers emerging for Alzheimer’s disease

This year, some new hope has dawned in the form of two promising medications for dementia – lecanemab and donanemab

Dr Stephen McWilliams, Consultant Psychiatrist, Saint John of God Hospital, Stillorgan

September 1, 2023

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  • During the last few years of her life, Dame Iris Murdoch, Dublin-born 20th-century philosopher and author of 26 novels, became known for a different, more tragic reason. Diagnosed with Alzheimer’s disease, she joined an ever-growing population of older people affected by the illness. A famously incisive thinker, Iris Murdoch first noticed the symptoms of her illness during the mid-1990s when she began to experience brief episodes of amnesia in one of her numerous public interviews. Moreover, her final novel – a psychological thriller entitled Jackson’s Dilemma (1995) – was noted by The New York Times to be “strewn with imprecisions and blatant redundancies” and paper was at a loss as to why the words “then suddenly” should appear three times in one short paragraph.

    Dementia, as we know, involves an impairment of higher cortical functions including memory, orientation, learning, thinking, calculation, language and judgement. Often associated with deterioration in motivation, emotional control and social behaviour, dementia occurs in clear consciousness and is usually chronic and progressive. The underlying illnesses include Alzheimer’s disease, vascular dementia, Lewy body dementia, Creutzfeldt-Jakob disease, Huntington’s disease and a variety of others. The prevalence of dementia increases with age, with the disease reportedly affecting 5% of 65-year-olds and 20% of 80-year-olds. There are currently an estimated 64,000 people with dementia in Ireland – a number that the HSE expects to more than double in the next 20 years.

    For years, the mainstay of pharmacological treatment for dementia were acetylcholinesterase inhibitors such as donepezil and rivastigmine. This year, some new hope has dawned in the form of two promising medications. In January 2023, Van Dyck et al reported on lecanemab, a humanised IgG1 monoclonal antibody that binds with high affinity to soluble aggregated beta-amyloid protein in the brain.1 In their paper in the New England Journal of Medicine, the authors described an 18-month, multicentre, double-blind RCT involving 1,795 participants with early symptomatic Alzheimer’s disease and observed “moderately less decline on measures of cognition and function than placebo at 18 months”, although the drug was associated with adverse events. 

    Donanemab similarly targets the build-up of beta-amyloid in the brain and was featured on RTE’s Prime Time in July. Dr Laura O’Philbin, research and policy manager at the Alzheimer Society of Ireland, described the new drug as a “game changer” and remarked on the absence of any new treatment for Alzheimer’s disease in some 20 years (see also page 57). A new study by Sims et al in the Journal of the American Medical Association described a multicentre, double-blind RCT involving 1,736 participants with early symptomatic Alzheimer’s disease.2 Half of the participants received donanemab intravenously every four weeks for 72 weeks. The medication “significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population”, according to the authors.  

    All of this means something. Iris Murdoch was a fellow of St Anne’s College, Oxford, and her prolific output of philosophical and fictional work included her masterpiece, The Sea, The Sea, for which she won the Booker Prize in 1978. Renowned throughout her life for her intellect and creativity, it is ironic that she should succumb to the very illness that would deprive her of these talents. The patient struck down with dementia leaves behind an interesting and unique life. Perhaps now there is some new hope.


    1. Van Dyck CH, Swanson CJ, Aisen P et al (2023). Lecanemab in early Alzheimer’s disease. N Engl J Med 2023; 388:9-21. doi: 10.1056/NEJMoa2212948
    2. Sims JR, Zimmer JA, Evans CD et al (2023) Donanemab in early symptomatic Alzheimer disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA, 2023 Jul 17 (online). doi: 10.1001/jama.2023.13239
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