The Three-City Study


Design, Rationale, and Objectives




The Three-City Study (3C-Study) is a population-based longitudinal study of the relationship between vascular diseases and dementia in adults aged 65 years and older. A total of 9,294 participants (3,649 men and 5,645 women) were recruited from three French cities: 2,104 in Bordeaux (South-West), 4,931 in Dijon (North-East), and 2,259 in Montpellier (South-East). Eligible participants were randomly sampled from electoral rolls.  Eligible individuals were persons 65 years or older at the time of recruitment, not institutionalized, and expecting to remain in the area for the next four years. All eligible individuals accepting to participate in the study were included. In other terms, there were no exclusion criteria. Among eligible individuals, about 40% agreed to participate in the 3C-Study and the acceptance rate was similar in the three cities.



Baseline workup included interviews and extensive cognitive, physical, and laboratory evaluations. More specifically, participants were subjected to a battery of cognitive tests and measurement of vascular risk factors (anthropometric measures, blood pressure, glycaemia, cholesterolemia, and other biological measurements). Carotid artery atherosclerosis was assessed by ultrasound examination in 6,612 participants aged less than 85 years. A subsample of 3,442 participants aged less than 80 years were subjected to cerebral magnetic-resonance imaging (MRI) to measure white matter lesions and cerebral volumes. Blood specimens were stored for future biological measurements and genetic studies.


The baseline examination of the cohort was performed between March 1999 and March 2001. Since then, participants have been re-examined, on the average, every two years. Each follow-up examination includes a labour-intensive ascertainment of the main outcomes of the study. Dementia, coronary heart disease (CHD) and stroke cases are validated by panels of independent experts.


For detailed description of data collected at baseline and at each follow-up, see Study Schedules and Data Collection.


In the mid-1990s, epidemiological studies suggested that the risk of dementia (all types, including Alzheimer’s disease) was increased in elderly persons with vascular risk factors. Factors that increased the risk of CHD and stroke, such as hypertension or diabetes, were also found to increase the risk of dementia, Alzheimer’s disease, and cognitive impairment, while factors that decreased vascular risk were associated with a lower incidence of cognitive disorders. This hypothesis was reinforced by clinical studies showing that white matter hyperintensities observed on cerebral MRI, considered as a marker of small cerebral artery disease, were associated with cognitive decline.

Principal Objective

The principal objective of the 3C-Study is to estimate the risk of dementia (Alzheimer’s disease and other types) that may be attributed to vascular factors. To reach this general objective, the following specific objectives must be attained:

  1. To assess the associations of vascular diseases (CHD and stroke) with dementia and cognitive impairment,
  2. To quantify the associations between cerebral white matter hyperintensities and dementia,
  3. To quantify the associations of dementia with factors that increase or decrease the risk of vascular diseases,
  4. To quantify the associations of cerebral measures (white matter hyperintensities and atrophy) with factors that increase or decrease the risk of vascular diseases.


The 3C-Study has many other important objectives described in Ancillary Studies.