Pharmacological Treatment of Mild Cognitive Impairment as a Prodromal Syndrome of Alzheimer's Disease

Abstract

Mild cognitive impairment (MCI) is a syndrome which, depending on various neurobiological, psychological and social factors, carries a high risk of developing into dementia. As far as diagnostic uncertainty and the heterogeneous underlying pathophysiological mechanisms are concerned, only limited therapeutic options are currently available. Clinical trials involving a wide range of substances have failed to show efficacy on primary and secondary outcome parameters. Most results reflect not only a lack of effectiveness of drug therapy but also methodological constraints in true prodromal Alzheimer´s disease (AD) based on clinical criteria. Biomarkers may help to identify MCI as a prodromal phase of dementia, so it is important to use them to improve specificity of case selection in future studies. For MCI as a prodromal syndrome of AD, clinical trials with disease modifying drugs that target underlying pathological mechanisms such as amyloid-beta accumulation and neurofibrillary tangle formation may help develop effective treatment options in the future. Alternative pharmacological approaches are currently being evaluated in ongoing phase 1 and phase 2 studies. Nevertheless, a lack of approved pharmacotherapeutic options has led to specific interventions that focus on patient education and life-style related factors receiving increasing attention.

Mitochondrial Perturbation in Alzheimer's Disease and Diabetes

“…MCI is generally considered to be a transitional phase between normal aging and early dementing disorders, especially AD. 121 …”

Transcranial direct current stimulation in mild cognitive impairment: Behavioral effects and neural mechanisms

“…Given that brain damage in AD may be too severe to be treated [2], research focuses on transitional stages between normal aging and dementia, such as mild cognitive impairment (MCI) [3]. Pharmacological interventions showed little positive impact in MCI trials [4]. Therefore, nonpharmacological interventions to treat MCI received increasing attention [5].…”

Efficacy of Cognitive Rehabilitation Therapies for Mild Cognitive Impairment (MCI) in Older Adults: Working Toward a Theoretical Model and Evidence-Based Interventions

“…Although a number of pharmacological strategies have been evaluated (e.g., acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, Vitamin E, rofecoxib, piracetam, memantine) or are under current investigation, these are reviewed elsewhere (Jelic et al 2006; Karakaya et al 2013; Popp and Arlt 2011) and are beyond the scope of the present paper. Instead, the current paper evaluates the efficacy of non-pharmacological interventions for MCI, specifically CRTs, by reviewing randomized controlled trials of such interventions (see Tables 2 and 3).…”