Clinical trials in mild cognitive impairment: lessons for the future

Abstract

Mild cognitive impairment (MCI) is an operational definition for a cognitive decline in individuals with a greater risk of developing dementia. The amnestic subtype of MCI is of particular interest because these individuals most likely progress to Alzheimer's disease (AD). Currently hypothesised therapeutic approaches in MCI are mainly based on AD treatment strategies. Long term secondary prevention randomised clinical trials have been completed in amnestic MCI populations, encompassing agents with various mechanisms of action: acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), antioxidants (vitamin E), anti-inflammatories (rofecoxib), and nootropics (piracetam). The design of clinical trials in MCI is influenced by study objectives and definition of primary end points: time to clinical diagnosis of dementia, and AD in particular, or symptom progression. As none of the drugs previously shown to have clinical efficacy in AD trials or benefit in everyday practice have met the primary objectives of the respective trials, design of future clinical trials in MCI should be further developed particularly as regards the selection of more homogeneous samples at entry, optimal treatment duration, and multidimensional and reliable outcomes.

Conflict of interest statement

Competing interests: the authors have not received research grants from any of the pharmaceutical companies marketing anti‐dementia drugs, neither have they have stocks in any of these companies. Dr Bengt Winblad received consultancy fees for advisory board meetings from most companies marketing anti‐dementia drugs. Dr Miia Kivipelto received consulting fees for an advisory board meeting from Pfizer. All authors received fees for lecturing or organising education sponsored by Novartis.

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