Symptomatic treatment for Alzheimer disease: current evidence and future directions

Symptomatic treatment remains central to the clinical management of Alzheimer disease (AD), even as disease-targeted therapies emerge. This Review synthesizes current evidence for pharmacological and non-pharmacological symptomatic therapies targeting cognition, function and neuropsychiatric symptoms in AD. Non-pharmacological interventions, including cognitive training, physical exercise, cognitive stimulation therapy and multimodal lifestyle programmes, show small-to-moderate benefits, particularly in mild cognitive impairment, although implementation challenges persist. Established pharmacological treatments, notably cholinesterase inhibitors and memantine, deliver modest but significant benefits, with biomarker-stratified analyses suggesting the greatest benefit in individuals with confirmed AD pathology. Advances in muscarinic agonists, multitarget agents, neurotrophic modulators and repurposed drugs highlight emerging opportunities for broader symptomatic benefit. Neuropsychiatric symptoms remain highly prevalent and burdensome; personalized psychosocial interventions demonstrate meaningful reductions in agitation and depression, whereas atypical antipsychotics offer only modest efficacy with substantial safety concerns. Newer agents, including brexpiprazole for agitation and pimavanserin for psychosis, show promise but require careful interpretation of effect size and safety. Future progress will depend on biomarker-informed patient selection, integration of circuit-level measures, rational combination strategies spanning pharmacological and non-pharmacological modalities, and adoption of patient-centred outcomes. Symptomatic therapies will remain essential for improving quality of life in people with AD, even as disease-targeted therapies reshape disease trajectories.