title: Methodological issues in primary prevention trials for neurodegenerative dementia.
abstract: The prevention of neurodegenerative dementias, such as Alzheimer's disease, is a public health priority. Due to the large numbers of affected patients, even interventions bringing about a relatively small delay in disease onset could have large public health effects. Randomized controlled trials (RCTs) are required to demonstrate the effectiveness of preventive interventions, but such trials raise specific methodological questions because they are new in the field of neurodegenerative diseases, and require large numbers of elderly subjects and lengthy follow-up periods. We performed a literature search to identify primary prevention RCTs for neurodegenerative dementia. The methodology of the trials was summarized and discussed during two expert meetings. Overall, 39 trials were identified that assessed dementia incidence or cognitive decline as a primary or secondary study outcome. Age was the most common selection criteria for target populations. Follow-up periods ranged from one month to nine years and were longest in studies measuring dementia incidence as an outcome. Results of RCTs have so far been generally negative and conflicting with those of observational studies, perhaps due to methodological issues. Future trials must therefore carefully consider the target population, outcomes and duration of follow-up to be used, and should assess the problem of attrition.
authors.affiliation: Inserm U558, Toulouse, France. sandrieu@cict.fr
authors.forename: Sandrine
authors.initials: S
authors.lastname: Andrieu
authors.forename: Nicola
authors.initials: N
authors.lastname: Coley
authors.forename: Paul
authors.initials: P
authors.lastname: Aisen
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.forename: Steven
authors.initials: S
authors.lastname: DeKosky
authors.forename: Jane
authors.initials: J
authors.lastname: Durga
authors.forename: Howard
authors.initials: H
authors.lastname: Fillit
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.forename: Lutz
authors.initials: L
authors.lastname: Froelich
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.forename: Roy
authors.initials: R
authors.lastname: Jones
authors.forename: Linus
authors.initials: L
authors.lastname: Jönsson
authors.forename: Zaven
authors.initials: Z
authors.lastname: Khachaturian
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Orgogozo
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Ousset
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Eric
authors.initials: E
authors.lastname: Salmon
authors.forename: Cristina
authors.initials: C
authors.lastname: Sampaio
authors.forename: Frans
authors.initials: F
authors.lastname: Verhey
authors.forename: Gordon
authors.initials: G
authors.lastname: Wilcock
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
mesh_terms: D000818:Animals; D003704:Dementia / Q000150:complications / Q000517:prevention & control*; D006801:Humans; D016239:MEDLINE / Q000706:statistics & numerical data; D019636:Neurodegenerative Diseases / Q000150:complications / Q000517:prevention & control*; D011322:Primary Prevention; D016032:Randomized Controlled Trials as Topic; D012107:Research Design