The potential for one drug, administered at the earliest preclinical stage, to prevent the subsequent decline of cognition that eventuates in dementia.

In the process that eventuates in mild cognitive impairment (MCI) and ultimately in Alzheimer's dementia, the earliest identifiable change is in the function of synapses. If started at that early point in time, when there is subjective but not objective memory loss plus abnormal brain imaging with fluorodeoxyglucose and Pittsburgh compound B, treatment with a single drug directed at synaptic dysfunction might prevent development of cognitive impairment. Each of four drugs, dantrolene, lithium, minocycline, and piracetam, benefits synaptic impairment. This presentation has two sections. In the first, evidence is discussed at length, for abnormality in the axo-spinous synapse as being the earliest change before objective cognitive decline. The second section explains the benefits to synapses provided by the four mentioned drugs. Dantrolene and lithium perhaps have the strongest supporting data for use as single agents: their efficacy should be subjected to clinical trial.

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© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

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