In this study, eligible patients had no
dementia, were at least age 60, and had
isolated systolic hypertension. Median follow-up by intention to treat was 2.0 years.
Compared with placebo (n = 1,180), active
treatment (n = 1,238) reduced the incidence
of dementia by 50%. The Syst-Eur trial was
stopped after the second of four planned
interim analyses because active treatment
had reduced stroke incidence, which was
the primary end point. Because of ethical
issues, however, the NASEM committee
questioned whether it is possible or practical to reach a definitive conclusion about the benefits of
blood pressure management for dementia using randomized controlled trial data.
Supplementary evidence in favor of blood pressure
management includes the link between cerebrovascular
disease and dementia, Dr. Petersen said, coupled with the
fact that antihypertensive drugs reduce stroke risk and
subclinical cerebrovascular disease. Prospective cohort
studies more consistently show an association between
blood pressure lowering and improved cognitive outcomes. Furthermore, in studies that were not randomized controlled trials, NASEM’s analyses using the Bradford Hill criteria suggested a causal relationship between
blood pressure management and decreased incidence of
Although the randomized controlled trial data on the benefits of physical activity were mixed, the results suggested
that physical activity could reduce the risk of age-related
cognitive decline. Data on the effect of physical activity
on the risks of MCI and Alzheimer’s-type dementia were
insufficient, Dr. Petersen said. Generally, follow-up periods were too short to assess long-term effects, and MCI
and Alzheimer’s-type dementia incidence were rarely
measured as outcomes.
“Findings from studies that compared the difference
between aerobic training and resistance training were
somewhat inconsistent,” Dr. Petersen said. “Some people
believe that a mixture of both may in fact be beneficial.”
In the largest randomized controlled trial examined, the
Lifestyle Interventions and Independence for Elders Pilot
study, evidence was insufficient to support conclusions
regarding a multicomponent intervention.
“There were observational studies and a variety of
longitudinal prospective studies that would suggest that
physical activity may have a positive effect
on cognitive performance and dementia in-
cidence,” Dr. Petersen said. “It could also
have an impact on other conditions that
may affect cognitive function, such as hy-
pertension, depression, and diabetes.”
Future Directions for Research
While the NASEM committee recommends
more research on the benefits of cognitive
training, blood pressure management, and
exercise training, it also urges the NIH and
other organizations to support studies with improved methodologies. Such improvements include identifying patients
at higher risk of cognitive decline or dementia, increasing
participation of underrepresented populations, beginning
interventions at younger ages, and establishing longer follow-up periods.
The committee also suggests that trials with other
primary purposes measure cognitive outcomes. “For in-
stance, if there is an ongoing study on prostate cancer,
and the researchers decide midway to add some cognitive
measure, that is useful,” Dr. Petersen said. “But it is not as
strong as if the study had been prospectively designed to
look at cognitive end points at the baseline.”
Other interventions that should be examined are new
antidementia treatments; treatments for diabetes and
depression; dietary, lipid-lowering, and sleep-quality
interventions; social engagement interventions; and
supplementation with vitamin B12 plus folic acid, said
Dr. Petersen. NR
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Ronald C. Petersen,