Cognition enhancing or neuroprotective compounds for the treatment of cognitive disorders: why? when? which?

Neurodegenerative disorders such as Alzheimer's disease, Lewy-Body dementia, Parkinson's disease and cerebrovascular dementia result in an insidious cognitive and behavioural decline culminating in the development of severe dementia. Based on current population projections it has been estimated that by 2050 the number of individuals over 65 will increase to 1.1 billion worldwide and as a consequence, the number of cases of dementia to 37 million. Faced with such an enormous public health and socio-economic burden it is evident that the importance of therapeutic intervention aimed at either finding a cure or preventing disease progression cannot be overstated. The aim of the present paper is to present an overview, in the context of a brain aging continuum, at what stage cognition enhancing and/or neuroprotective intervention strategies aimed at stabilising and/or preventing neurodegenerative disease could demonstrate potential clinical benefit. In particular, the clinical identification of patients with mild cognitive impairment and age-associated memory impairment which may represent a ‘transition’ state between normal aging and dementia is discussed as a potential clinical population cohort targeted for early intervention in dementia. Considering the wide spectrum of cognitive and psychotic effects in dementia juxtaposed with the neuropathological evolution of the disease, it is clear that a variety of therapeutic intervention(s) will be required in order, to at the least, stabilise disease progression. Evidently, since Alzheimer's disease is by far the most prevalent form of dementia, and will undoubtedly serve as the benchmark for any future treatment of dementia, an update of current symptomatic and disease-modifying therapeutic approaches (cholinergic, glutamatergic, nootropics, β-amyloid cascade inhibitors) will be reviewed.