French MAPT Cohort

PI:  Bruno Vellas, MD

Contact person: 

Sophie Gillette, [email protected]
Claire Vinel, [email protected]

Contact method:  Please apply for access through the VRADB.

VRADB Application required for access?  Yes.  Information about the application process can be found here.

Study Description:

The MAPT study is a 3-year, randomized, controlled trial conducted by university hospital practitioners specializing in memory disorders in 13 French cities. The study enrolled 1680 frail elderly subjects. To demonstrate the protective effect of interventions, subjects are randomized into one of the following four groups: omega 3 alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo (n=420 each). The principal outcome measure is a change in cognitive function at 3 years, as determined by the Grober and Buschke Test.

Secondary objectives include the collection of biological material (blood specimens, RNA, and genomic DNA) to identify new biomarkers of potential use in future AD prevention and treatment trials, assessments of the efficacy of intervention (multidomain or omega 3 treatment) on functional decline and functional capacities, and compliance. In addition, neuroimaging neuroimaging examinations (positron emission tomography [PET] scans and magnetic resonance imaging [MRI]) will be performed in a subgroup of participants to identify the impact of interventions (multidomain or omega 3 treatment) on cerebral atrophy and cerebral metabolism. Body-composition assessments (dual energy X-ray absorptiometry [DEXA]) will also be used to study the potential influence of body composition changes on frailty and cognitive decline.

Study design: Participants are randomized into a group in each city by an interactive voice response system, according to a list of random numbers in blocks of 8 generated by the industrial study sponsor. Visits are scheduled every 6 months to assess physical condition, diseases and corresponding treatments, adherence to and tolerance of omega 3 treatment, and adherence to the multidomain intervention, and to deliver the supplement. Cognitive and functional assessments are conducted at baseline, at 6 months, and annually at 1, 2, and 3 years by independent research staff who do not know the group to which the subject is assigned (tools used for assessments include : IADL/ADL, MMSE, DSM IV, Grober & Buschke, trail making Test A & B, EVA, CNT, COWAT, CDR, SPPB, Fried’s criterion, ADCS-ADl PI, GDS). All assessments are performed by hospital practitioners specializing in memory disorders and AD.The study protocol was approved by the Institutional Review Board of Toulouse (i.e., the coordinating center). Written, informed consent is obtained from all participants.

More information about the French MAPT Study can be found here.

Subjects:

The recruitment goal for the MAPT trial is to enroll a sample of frail elderly people, aged 70 years and over, living in dependently, with good functional and cognitive status. We used three clinical components to identify frail persons based on epidemiological evidence: spontaneous memory complaint expressed to a general practitioner, limitation in one instrumental activity of daily living (IADL, i.e, ability to use the telephone, shop, prepare meals, to housekeeping, do one’s laundry, use transportation, follow a medication schedule, or manage money), and slow walking speed (speed lower than o.8 m/s, which means that it takes more than 5 seconds to walk 4 m).

We excluded demented subjects (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DMSM IV] criteria), subjects who had a Mini-Mental State Examination (MMSE) score lower than 24 (0-30), subjects who were incapable of basic activities of daily living (ADL score lower than 6 [0-6]), and those who were severely depressed (Geriatric Depression Scale [GDS] score of 15). In addition, other disorders that could interfere with the interpretation of the study were evaluated, and patients with such disorders were excluded. Participants were enrolled from various sources, including advertisements in the local media, conferences, general practitioners, and memory clinics in 13 French cities. The inclusion period began in June 2008 and was closed in February 2011.

The sample size required for this trial is based on a 0.3-SD difference between the four trial arms (three treatment groups plus placebo group) according to a free recall score in the Grober and Buschke test over the 3 years of the intervention. To detect a 0.3-SD difference between trial arms, with an alpha risk of 1% and a power of 80% power, 201 individuals are required per group. Anticipating a 30% dropout over 3 years of intervention, the total sample sized required for the study is 1148 (287 per group).

Material Available:

Plasmas samples were collected from the first visit, than 12, 24 and 36 month after. At present, we have collected 919 blood samples for the baseline visit, 1166 at 12 months, 725 at 24 months and 175 at 36 months. Plasmas for DNA and proteins studies are collected in dry tubes and blood sample for ARN studies are collected in PAXgenes tubes.

Collection Methods:

10 ml of blood are collected in EDTA tubes then 5ml of blood are collected in PAXgenes tubes, all tubes are gentle mixed, then put at 4°C or at room temperature for 2h. Samples are transferred from each site to Toulouse at 4°C, then freezed at -80°C.

Storage:

All blood samples are stored at -80°C.

Other Measurements available for this cohort:

For subsamples, we have other measurements such as DEXA for body composition, PET-scan (amyloid imaging and metabolism), MRI.

Related Publications:

Sophie Gillette-Guyonneta,Sandrine Andrieu, Thierry Dantoine, Jean-Francois Dartigues, Jacques Touchon, B. Vellas, MAPT Study Group (2009).  Commentary on ‘‘A roadmap for the prevention of dementia II. Leon Thal Symposium 2008.’’ The Multidomain Alzheimer Preventive Trial (MAPT): A new approach to the prevention of Alzheimer’s disease.  Alzheimer’s & Dementia 5 (114–121).