Treatment of mild cognitive impairment: rationale, present and future strategies

Mild cognitive impairment (MCI) is a condition with a high conversion rate to Alzheimer's disease (AD), which justifies early diagnostic and therapeutic interventions. At the moment, treatment strategies for AD could be extrapolated to interventional strategies in MCI. This article reviews currently available symptomatic treatments with acetylcholinesterase inhibitors, putative treatments such as antiglutamatergic drugs, nootropics, antioxidants, anti-inflammatory drugs and still controversial estrogen replacement therapy, and visionary treatments targeting neuropathological substrates of the disease, such as amyloid production and aggregation, phosphorylation of tau, formation of neurofibrillary tangles and apoptosis. Findings from epidemiological studies have expanded our knowledge on risk as well as possible neuroprotective factors and given means to develop preventive strategies with antihyperlipidaemic drugs such as statins. A wide range of suggested treatments and their possible combinations necessitate their efficacy assessment in well-designed randomized clinical trials where the crucial prerequisites are selection of the treatment population and definitions of outcome measures. Prevention and disease-modifying strategies are raising ethical questions because interventions are focused on nondiseased elderly at risk, which means that emphasis should be not only on efficacy but also on long-term safety.