Methodological issues in primary prevention trials for neurodegenerative dementia.
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.
Andrieu
Sandrine
S
Inserm U558, Toulouse, France. sandrieu@cict.fr
Coley
Nicola
N
Aisen
Paul
P
Carrillo
Maria C
MC
DeKosky
Steven
S
Durga
Jane
J
Fillit
Howard
H
Frisoni
Giovanni B
GB
Froelich
Lutz
L
Gauthier
Serge
S
Jones
Roy
R
Jönsson
Linus
L
Khachaturian
Zaven
Z
Morris
John C
JC
Orgogozo
Jean-Marc
JM
Ousset
Pierre-Jean
PJ
Robert
Philippe
P
Salmon
Eric
E
Sampaio
Cristina
C
Verhey
Frans
F
Wilcock
Gordon
G
Vellas
Bruno
B
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