Three quarters of patients with Alzheimer's disease have at least one vascular risk factor (VRF). Vascular brain lesions are present in most Alzheimer's patients (especially older ones). This cerebrovascular disease potentiates Alzheimer's lesions in early-stage disease. Many research studies have shown that VRFs are also risk factors for Alzheimer's disease; this is true for arterial hypertension and dyslipidaemia in particular and, to a lesser extent, diabetes and cardiopathy. Moreover, recent drug trials (SYST-EUR, PROGRESS and HOPE) have indicated that antihypertensive medications can prevent the appearance of dementia (and notably Alzheimer's disease) in over-60 hypertensive subjects. An observational study of 233 Alzheimer's patients with an average follow-up period of 4 years has shown that the annual decline in the Mini-Mental State Examination (MMSE) score was lower in patients in whom all the VRFs were being treated than in patients in whom no VRFs were being treated (1.5 ± 2.5 points versus 2.5 ± 2 points, respectively; p<0.04).1 However, it is not currently known whether optimal treatment of VRFs can influence the progression and prognosis of Alzheimer's disease. Answering this question could have a significant impact on public health.

Brief Title

Impact of Controlling Vascular Risk Factors on the Progression of Alzheimer's Disease

Official Title

Impact of Controlling Vascular Risk Factors on the Progression of Alzheimer's Disease

Brief Summary

Three quarters of patients with Alzheimer's disease have at least one vascular risk factor <br /> (VRF). Vascular brain lesions are present in most Alzheimer's patients (especially older <br /> ones). This cerebrovascular disease potentiates Alzheimer's lesions in early-stage disease. <br /> Many research studies have shown that VRFs are also risk factors for Alzheimer's disease; <br /> this is true for arterial hypertension and dyslipidaemia in particular and, to a lesser <br /> extent, diabetes and cardiopathy. Moreover, recent drug trials (SYST-EUR, PROGRESS and HOPE) <br /> have indicated that antihypertensive medications can prevent the appearance of dementia (and <br /> notably Alzheimer's disease) in over-60 hypertensive subjects. An observational study of 233 <br /> Alzheimer's patients with an average follow-up period of 4 years has shown that the annual <br /> decline in the Mini-Mental State Examination (MMSE) score was lower in patients in whom all <br /> the VRFs were being treated than in patients in whom no VRFs were being treated (1.5 ± 2.5 <br /> points versus 2.5 ± 2 points, respectively; p<0.04).1 However, it is not currently known <br /> whether optimal treatment of VRFs can influence the progression and prognosis of Alzheimer's <br /> disease. Answering this question could have a significant impact on public health.

Detailed Description

It is not currently known whether the optimum treatment of VRFs influences the progression
and prognosis of Alzheimer's disease. Our starting hypothesis is that VRF control in
Alzheimer's patients is associated with slower cognitive decline, less intense loss of
personnel independence and fewer adverse events over the course of the disease
(cardiovascular or cerebrovascular events, behavioural disorders, caregiver burden,
hospitalization and death).

COVARAD study is a randomized, controlled, multicentre study comparing 2 VRF care strategies
in mild-to-moderate (MMSE > 18) Alzheimer's disease patients with at least one VRF. The
objective of this work is to evaluate the effect of "optimal" care strategy, in strict
compliance with the French HAS guidelines concerning targets for blood pressure, glycaemia
and blood lipid levels, on the cognitive function in mild-to-moderate Alzheimer's patients
(MMSE score > 18), in comparison with a control group (i.e. receiving standard care from a
primary care physician). The study test the hypothesis whereby "optimal" care of the 3 main
modifiable VRFs is associated with slower cognitive decline in Alzheimer's disease patients
(evaluated on the ADAS-cog score), when compared with standard care and to compare the MMSE,
MoCA and VADAS-cog scores, mood and behaviour (MADRS and NPI), loss of independence
(ADCS-ADL), the occurrence of cardiovascular or cerebrovascular events, the number and length
of hospitalisations, caregiver burden (on the Zarit scale), institutionalization and survival
in the two groups (i.e. depending whether VRFs are managed optimally or not).

This study could influence clinical practice. If VRF control does have an influence on the
progression of Alzheimer's disease, an information campaign could modify practice and have a
significant impact on public health.

An independent Data and Safety Monitoring Board will be set up to monitor the diabetic
patients, in view of the risks related to "optimal" care (ACCOR and ADVANCE studies).
Nevertheless, the risk of adverse events will be limited by raising the threshold value for
glycated haemoglobin to 8%.