Advances in the prevention of Alzheimer's disease and dementia

Abstract

Background: Definitions and diagnostic criteria for all medical conditions are regularly subjected to reviews and revisions as knowledge advances. In the field of Alzheimer's disease (AD) research, it has taken almost three decades for diagnostic nomenclature to undergo major re-examination. The shift towards presymptomatic and pre-dementia stages of AD has brought prevention and treatment trials much closer to each other than before.

Methods: Here we discuss: (i) the impact of diagnostic reliability on the possibilities for developing preventive strategies for AD; (ii) the scientific evidence to support moving from observation to action; (iii) ongoing intervention studies; and (iv) the methodological issues and prospects for balancing strategies for high-risk individuals with those for broad population-based prevention.

Results: The associations between neuropathology and cognition are still not entirely clear. In addition, the risk factors for AD dementia and the neuropathological hallmarks of AD may not necessarily be the same. Cognitive impairment has a clearer clinical significance and should therefore remain the main focus of prevention. Risk/protective factors for dementia/AD need to be studied from a life-course perspective. New approaches in prevention trials include enrichment strategies based on genetic risk factors or beta-amyloid biomarkers (at least four ongoing pharmacological trials), and multidomain interventions simultaneously targeting various vascular and lifestyle-related risk factors (at least three ongoing trials). Experience from prevention programmes in other chronic diseases can provide additional methodological improvements.

Conclusions: Building infrastructures for international collaborations is necessary for managing the worldwide public health problem of AD and dementia. The International Database on Aging and Dementia (IDAD) and the European Dementia Prevention Initiative (EDPI) are examples of ongoing international efforts aiming to improve the methodology of preventive studies and provide the basis for larger intervention trials.

Keywords: Alzheimer's disease; biomarkers; clinical trials; dementia; prevention.

Conflict of interest statement

Conflict of interest statement

I. Skoog has been on the speaker’s bureau for Takeda, Esai, Shire, Lundbeck, Jansen and Pfizer.

He has been a consultant fo Takeda.

S. Andrieu has received consulting fees or payment or institutional grant from Beaufour Ipsen Pharma SAS; Esai Inc; Pierre Fabre Laboratories; Pfizer, Eli Lilly and Company, Lundbeck Inc.; Nestle S.A.; Novartis; Roche; Servier, Janssen; Exhonit; Chiesi; Sanofi.

© 2014 The Association for the Publication of the Journal of Internal Medicine.

Figures

Fig. 1

PubMed articles with prevention-related keywords, listed up to June 2013, in the field of cognitive disorders in elderly populations.

Fig. 2

Scheme showing how different definitions of AD can lead to different definition of primary, secondary and tertiary prevention in AD. Definition 1, according to the National Institute of Aging-Alzheimer Association workgroup; definition 2, according to Dubois et al.[2]

Fig. 3

Different characteristics can be considered when targeting preventive measures leading to the identification of different populations.