ONGOING STUDIES

DESCRIPA

Development of Screening guidelines and diagnostic Criteria for Predementia Alzheimer's disease

acronym : DESCRIPA (Development of Screening guidelines and diagnostic Criteria for Predementia Alzheimer's disease)

The project DURATION will be four years.


OBJECTIVES AND EXPECTED ACHIEVEMENTS

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders with a prevalence rising from 0.2% in subjects between 55 and 65 years to 27% in subjects older than 85 years (Ott et al., 1995) . The first symptom of AD are mild cognitive complaints. These cognitive complaints gradually become more severe until dementia is present at the end stage of the disease. According to the presently available diagnostic criteria for AD, the diagnosis of AD can only be made when a subject is demented (McKhann et al., 1984).

Tools for diagnosing subjects with AD before they become demented, i.e. when they are in the predementia phase, are urgently needed for several reasons:

  • First, it will give the opportunity to start treatment in an earlier phase than is possible now. Treatment that is now available for these patients, such as psychosocial interventions and drugs that have been shown to improve cognition in subjects with AD-type dementia, are likely to improve the quality of life of patients with predementia AD by improving cognitive functioning, functional independency, autonomy, and social integration. The early start of treatment will be very important if drugs become available that can delay or slow down the progression of the disease. Drugs that have the potential to do so are now being developed and are likely to become available for clinical trials within a few years.
  • Second, an early diagnosis may bring relief, may end uncertainty about the cause of the cognitive impairment, and may give the opportunity to anticipate the future (Robinson et al., 1998) .

In order to identify subjects in the predementia stage, diagnostic criteria for predementia AD and screening guidelines that can be used in the general population are needed. However, there are no specific diagnostic criteria for predementia AD. Criteria have been developed for subjects who have mild cognitive complaints but these criteria can not serve to identify subjects with predementia AD in clinical practice because of the poor sensitivity (52%) despite the modest to good positive predictive value (60-80%) (Petersen et al., 1999; Visser et al., in press-a) . Screening guidelines for predementia AD are not available either, although a number of population-based studies have indicated that subjects with predementia AD can be identified in the general population by markers of AD.

Thus, there is a need for studies that will develop diagnostic criteria for predementia AD in a clinical setting and screening guidelines in the general population. From a methodological point of view, these diagnostic criteria and screening guidelines should preferably be developed using an evidence-based or data-driven approach rather than an expert-based approach. In addition, the criteria and guidelines should be developed in a international setting in order to ensure validity of the criteria and guidelines across countries. It would be highly recommendable that the criteria and guidelines would be developed in a European setting in order to facilitate the development of therapeutic strategies to AD that are currently being initiated by the EC-funded European Alzheimer's Disease Consortium (EADC).


The PRIMARY GOAL

of the project will be to perform a concerted action in order to reach an evidence-based European consensus on the identification of subjects with AD in the predementia stage.



The SECONDARY GOALS of the project will be:

  • the development of diagnostic criteria for predementia AD in a clinical setting.
  • the development of screening guidelines for predementia AD in the general population.


These goals will be achieved by meeting the following OBJECTIVES:

  • To pool data from six European prospective clinical studies of subjects with mild cognitive complaints in which markers of predementia AD such as demographic variables, cognitive functioning, brain atrophy, b-amyloid 1-42 and tau concentrations in the cerebrospinal fluid (CSF), and the apolipoprotein E genotype have been investigated and that have been performed in neurological, geriatric or psychiatric-based outpatient clinics.
  • To develop diagnostic criteria for predementia AD in a clinical setting on the basis of these pooled data.
  • To analyse data from five prospective European population-based studies that have investigated the diagnostic accuracy of demographic variables, cognitive variables, and the apolipoprotein E genotype for predementia AD.
  • To develop screening guidelines for predementia AD in the general population on the basis of these European population-based studies.
  • To organize workshops and symposia at major psychogeriatric conferences in order to discuss the results with the user groups, i.e. clinicians, researchers, patient organizations, and pharmacological compagnies, and to disseminate the results to them.
  • To construct a database of blood and CSF samples that can be used for future research on diagnostic markers of predementia AD.

Project Manager: Dr. P.J. Visser



Centres participants :

  • The Netherlands
    Institute of Brain and Behavior - University Maastricht
    Prof F.R.J. Verhey and Prof J. Jolles
  • Italy
    Laboratory of Epidemiology and Neuroimaging
    IRCCS San Giovanni - Brescia
    Prof G Frisoni, Prof O Zanetti

    Clinical Neurophysiology
    Dept. of Neuroscience, Ophthalmology and Genetics, University of Genoa
  • The Netherlands
    Department of Neurology, VUMC - Amsterdam
    Prof. P. Scheltens and Prof C. Jonker
  • Sweden
    Karolinska Institute( KI) - Huddinge
    Prof L-O Wahlund and Prof B. Winblad
  • France
    INSERM-E99-30 - Montpellier
    Dr. K. Ritchie and Prof J. Touchon
  • Greece
    University of Thessaloniki
    Prof M. Tsolaki



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