Header image
 
early diagnosis of Alzheimer’s disease  
line decor
  
line decor
 
 
 
 

 
 
Project outline
 

Title: Development of screening guidelines and criteria for predementia Alzheimer’s disease

Acronym: DESCRIPA

Contract number: QLK-6-CT-2002-02455

Project type: Concerted Action

EC contribution in euro: 399.997

Starting date: 1 January 2003

Duration: 54 months

Background and objectives:
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders. The diagnosis of AD can currently be made only if a subject is demented. However, subjects with AD already experience symptoms before they are demented. It would be important to identify subjects with AD in the predementia stage, as this will allow to start interventions that may improve cognition or prevent the progression of the disease in an earlier stage than is possible now.

The overall aim of the study was to reach an evidence-based European consensus on the identification of subjects with AD in the predementia stage.
The specific aims were:
- The development of diagnostic criteria for predementia AD in a clinical setting.
- The development of screening guidelines for predementia AD in the general population.

Approach and methodology:
Development criteria for predementia AD
Clinical criteria will be developed on the basis of a prospective cohort study of 880 subjects with mild cognitive impairments from 20 outpatient memory clinics in 11 European countries. Inclusion criteria were referral because of cognitive impairment and age above 55 year. Exclusion criteria were medical conditions that cause cognitive impairment.
Baseline assessment. At baseline, a number of variables were collected that could be a diagnostic marker for predementia AD. The study had a pragmatic design closely following standard clinical procedures. As a result, rating scales and cognitive tests could vary between centres and some predictor variables were investigated in a subset of centres only. The variables investigated are shown in table 1. In addition, blood and cerebrospinal fluid was stored for future analysis with new diagnostic markers.
Follow-up assessment. Subjects received annual follow-up assessments for 2 to 3 years. The diagnosis of predementia AD at baseline was made if the patient met criteria for probable or possible AD at follow-up.
Data analysis. The criteria of predementia AD will be based on the variables collected at baseline and the outcome at follow-up. The primary outcome measure is AD-type dementia at follow-up. Because subjects with predementia AD may convert to AD-type dementia at longer follow-up intervals, a secondary outcome measure of cognitive decline was used. This outcome measure included all subjects with AD-type dementia at follow-up and also non-demented subjects with persistent memory impairment or memory decline. Two approaches will be used to develop these criteria. The first approach is based on the Preclinical Alzheimer's Disease Scale (PAS, Visser et al.2002, J Neurol 249:312-319, www-np.unimaas.nl/scales/pas). The second approach will be data driven and makes use of stepwise multivariate logistic regression.
Time planning. The data collection started 1 January 2003 and at 1 July 2007 the 2-year follow-up was completed. Data analysis is ongoing. It is planned to extend the follow-up to 5 years.


Table 1. Variables used for the development of clinical criteria

Demographic variables
Cardio-vascular and psychiatric disorders
Impairment in activities of daily living
Score on the MMSE
Performance on tests for memory, language, attention, executive function, and visuoconstruction
Atrophy of the medial temporal lobe and white matter lesions on a MRI scan (n=376)
Levels of tau protein, phosphorylated tau, and beta-amyloid 1-42 in cerebrospinal fluid (n=188)
The apolipoprotein E genotype (n=435)
Amplitude changes on quantitative electroencephalography (n=196)
Perfusion on SPECT scans (n=154)

'n' refers to the number of subjects in which the variable was assessed.

Development screening guidelines for predementia AD
Screening guidelines will be based on a meta-analysis of 8 ongoing population-based studies in Europe. These studies are: the Maastricht Aging Study (MAAS), the Longitudinal Aging Study Amsterdam (LASA), the Italian Longitudinal Study of Aging (ILSA), the Eugeria study of cognitive aging, the Personnes Agées QUID study (PAQUID), the Prospective Population Study of Women and the Gerontological and Geriatric Population Study (H70 study) in Gothenburg, and the Leipzig Longitudinal Study of the Aged (LEILA 75+). Subjects were included that did not have dementia at baseline.
Baseline assessment. The baseline assessment varied between the studies. Therefore, not all diagnostic markers or risk factors were available for all studies. The variables investigated are shown in table 1.
Follow-up assessment. Subjects were reassessed at intervals of 1 to 3 years and subjects with dementia and Alzheimer-type dementia were identified. The follow-up length was between 2 and 12 years depending on the study. The diagnosis of predementia AD at baseline was made if the patient met criteria for probable or possible AD at follow-up.
Data analysis. The screening guidelines of predementia AD will be based on the variables collected at baseline and the outcome at follow-up. The main outcome measure is a diagnosis of AD-type dementia at follow-up. Secondary analyses will be conducted with dementia at follow-up as outcome measure. Two approaches will be used. The first approach is based on the PAS (see above). The second approach will be data driven and makes use of stepwise multivariate logistic regression.
Time planning. Data pooling started 1 January 2006 and is currently being finalized.

Table 2. Variables used for the development of screening guidelines


Demographic variables
Cardio-vascular and psychiatric disorders
Smoking and drinking habits
Medication use
Body mass index
Impairment in activities of daily living
Score on the MMSE
Performance on tests for memory, language, attention, and executive function
The apolipoprotein E genotype

 

Results:
The data analysis is ongoing.