Prevention of Alzheimer disease
Epidemiologic studies have suggested that the consumption of
several medications is associated with a reduced risk of dementia.
These products include nonsteroidal anti-inflammatory
drugs,17 vitamin supplements,48 and estrogens in women.49 In
the case of nonsteroidal anti-inflammatory drugs, the most recent
meta-analysis, of 25 observational studies, concluded that
the risk of all-cause dementia was significantly lower among
study participants exposed to these drugs than among those who
had not taken them.18 However, a recently published randomized
controlled trial of celecoxib (200 mg twice daily), naproxen
(220 mg twice daily) and placebo in cognitively healthy participants
was ended early because of concerns about drug safety and
lack of effect, since no delay or reduction in the onset of dementia
was observed.50 Thus, there is no justification for recommending
the use of nonsteroidal anti-inflammatory drugs for the
primary prevention of Alzheimer disease. Recent systematic reviews
have also concluded that, in the absence of evidence from
randomized controlled trials, there is no justification for consuming
antioxidant vitamins C and E with the intention of reducing
the risk of subsequent Alzheimer disease.51 Furthermore,
doses of vitamin E greater than 400 IU/d have been shown to
have negative cardiovascular effects.52 Studies of B vitamins are
inconclusive and are considered in a later article in this series.
Recommendations based on studies other than randomized
controlled trials must be made with extreme caution. Estrogen
hormone replacement therapy was widely recommended for
the prevention of cardiovascular disease on the basis of case–
control, epidemiologic and biological studies. Definitive, randomized
controlled trials such as the Women’s Health Initiative
proved that the risks of myocardial infarction and stroke
were actually increased with the use of such therapy. The
Women’s Health Initiative Memory Study, a large randomized
controlled trial of estrogen and progesterone replacement therapy
in over 7000 women aged 65–79 years, revealed that the
risk of dementia was increased with the use of estrogen either
alone or in combination with progesterone. This finding effectively
extinguishes recommendations for hormone replacement
therapy for the prevention of dementia.53