journal articles
UPDATE ON PREVENTION TRIALS IN ALZHEIMER’S DISEASE
B. Vellas
J Prev Alz Dis 2014;1(3):168-175
An evolving consensus about the need to treat AD in the
presymptomatic phase has emerged following the
disappointing results of several trials that enrolled subjects with
mild to moderate disease, as well as accumulating research
demonstrating that AD pathologic process begins decades
before the appearance of symptoms. Several lessons can be
learned from past prevention trials. The targeted populations
were too diverse, the interventions probably not strong enough,
and the time of exposure was most likely too short. We have
learned from these trials that future prevention trials must be
targeted, use strong interventions with known biological
activity, and must be sustained with a long-term intervention.
In this paper, we focus on three prevention trial approaches:
A. Targeted therapy: Preventing AD by targeting a specific
population with a specific intervention. Such preventive
approaches and trials must be based on biomarkers and
imaging to select a study population in accordance with the
mechanism of the specific intervention;
B. Multi-domain interventions targeting a larger, more diverse
population over a longer time period with long-term exposure
to non-specific, multi-domain intervention. The rationale for
this approach stems from studies showing that several
environmental factors are associated with the risk of developing
dementia. These factors may include educational level, vascular
and metabolic risk factors, physical activity, cognitive
stimulation, and nutritional status. It may also be possible to
identify healthy adults at high risk of AD and likely to benefit
from intervention based on subjective memory complaint,
ApoEε4 carriage, family history of AD, or the presence of
frailty; and use multidomain interventions to compensate for
low specificity;
C. What will be probably the future of clinical practice: A
preventive approach, integrated into primary care settings that
begins with longitudinal monitoring of memory function in a
general population to identify decliners, followed by a specific
intervention based on biomarkers and imaging discussed case
by case. Finally, preventing AD will require new and improved
infrastructure.
CITATION:
B. Vellas (2014): UPDATE ON PREVENTION TRIALS IN ALZHEIMER’S DISEASE. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2014.30