From successful aging to severe dementia

A recently published special issue of the Journal of Alzheimer's Disease contains the contributions from experts in the field of aging, dementia and Alzheimer's disease, who attended the "Fourth Annual Meeting on Brain aging and Dementia - From successful aging to severe dementia”, Held in Perugia in October 2006 under the auspices of the Italian Psychogeriatric Association, a member of the International Psychogeriatric Association, the meeting celebrates the centenary of Alzheimer's first description of the disease.

The articles cover several topics on AD: sociological, epidemiological, clinical and biological aspects offer a wide overview on this multifaceted disease.

Robert Binstock, from Case Western Reserve University, Cleveland (USA), reports some reflections on the ethical, moral and policy challenges for healthcare professionals and politicians due to the aging of industrialized nations. This social phenomenon is associated with an enhanced demand for both acute and long-term healthcare for the elderly that will increasingly strain economic resources.

Laura Fratiglioni and Hui-Xin Wang, from the Karolinska Institute of Stockholm (Sweden), review the concept of “brain reserve” that refers to the ability to tolerate the age-related changes and disease-related pathology in the brain without developing clear clinical symptoms. Epidemiological studies indicate that brain reserve is related to a number of aspects including high education, adult-life occupational work complexity, as well as a mentally and socially integrated lifestyle.

Guest Editor Patrizia Mecocci and colleagues from the Italian University of Perugia (Elena Mariani) and University of Palermo (Roberto Monastero) review the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of Mild Cognitive Impairment, a nosological entity proposed as an intermediate state between normal aging and dementia, with specific attention to possible markers of conversion to dementia.

Ezio Giacobini and Robert Becker from the University of Geneva (Switzerland) expand on possible treatments of AD that should modify the course of the pathological processes at the basis of this disease. Several active and passive vaccines against amyloid-â humanized antibody, drugs aiming to reduce tau phosphorylation (GSK3 inhibitors), anti-amyloid-aggregation and anti-APO-E molecules are considered, while the developments of gamma-and beta-secretase inhibitors, due to intrinsic difficulties, seem to have not yet reached the clinical stages.

Clive Ballard and his colleagues Susanne Sorensen and Samantha Sharp from King's College, London (UK) give a brief overview of the clinical effectiveness of cholinesterase inhibitors for the treatment of Alzheimer's disease, discuss in detail the NICE appraisal of these treatments in the UK as a example of an attempt at a standardized evaluation of cost-effectiveness and argue a proposed way forward to achieve a unified and consistent approach to the assessment of cost-effectiveness for anti-dementia therapies.

Allan Butterfield and Rukhsana Sultana from the University of Kentucky, Lexington (USA) write of their studies on oxidative stress in AD and MCI brain indexed by protein oxidation and lipid peroxidation and summarize findings of oxidatively modified proteins using redox proteomics approach in AD and MCI brain aimed to investigate the mechanism that may be involved in their pathogenesis as well as in terms of MCI progression to AD.

Alessandro Serretti, Paolo Olgiati and Diana De Ronchi, from the University of Bologna (Italy) discuss the genetics of Alzheimer's disease, focusing on the sporadic form in which most genes, related to the amyloid-â deposition, oxidative stress and inflammatory response are involved. They report that genetic mechanisms are also involved in expression of depression and psychotic symptoms that occur in a large proportion of AD patients and in the therapeutic effect of drugs currently used.

Cristina Lanni and colleagues from the University of Pavia (Italy) discuss the methodologies that have been used to identify an altered conformational status of p53 in fibroblasts of AD patients. They explain that this alteration may be related to exposure to low amounts of soluble Aâ peptide, not resulting in cytotoxic effects. On this basis, they hypothesize that unfolded p53 could be considered as an agent participating in the early pathogenesis and as a specific marker of the early stage of AD.

Finally, Eugenio Mocchegiani and Marco Malavolta from INRCA (National Institute of Research and Cure for the Elderly) of Ancona (Italy) write about the role of zinc homeostasis in different conditions of brain dysfunction, including brain inflammatory status, aging brain and neurodegeneration They also discuss the role played by metallothioneins (which regulate the intracellular free zinc ions) and á2 macroglobulin (a zinc-binding protein) in aging and AD.