Low dose aspirin and cognitive function in the women's health study cognitive cohort
BMJ 2007; 334 doi: https://doi.org/10.1136/bmj.39166.597836.BE (Published 10 May 2007) Cite this as: BMJ 2007;334:987
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The recent editorial by Kang et al (1) further add to the uncertainty
in
recommending the appropriate dose of aspirin to women (2). The WHS used a
low dose of aspirin, 100 mg every other day , that is lower than the
typical
"low dose" used for cardiovascular risk reduction in the United States,
81mg
daily in order to improve the overall safety profile. To directly
investigate if
these two doses had different effects on overall platelet function, we
assessed the effect on platelet inhibition of two different aspirin
dosing
regimens: 100 mg every other day and 81 mg daily.
We enrolled 49 healthy female volunteers with same characteristics as
those
in WHS and used a sequential, crossover design to compare the two
regimens. The participants received a 17-day course of each aspirin-
dosing
regimen separated by a 7-day washout period. The degree of platelet
inhibition of each dosing regimen was measured using a validated point-of-
care platelet function assay utilizing arachadonic acid to activate
platelets (3).
Participants platelet response attained a significantly greater level of
platelet
inhibition and less day- to-day variability while taking aspirin 81 mg
daily
compared to aspirin 100 mg every other day (31.3% vs. 12.7%, p <
0.0001).
We found significantly less inhibition of platelet function with the
dose used
in the WHS than the usual U.S. dose, suggesting that results of the
Women's
Health Study may have underestimated the efficacy and toxicity of aspirin
as
it is commonly administered. These data support the use of at least
aspirin
81 mg daily for primary prevention and raises the issue as to whether
measurement of platelet function to determine if a patient is attaining
adequate inhibition may improve therapy. These data need to be considered
when extrapolating the efficacy and safety data from the WHS to U.S. women
and comparing it to other studies.
1. Kang JH, Cook N, Manson J, Buring JE, and Grodstein F.,
Low dose aspirin and cognitive function in the women's health study
cognitive
cohort, BMJ 2007
2. Ridker, P.M., et al., A randomized trial of low-dose aspirin in the
primary
prevention of cardiovascular disease in women. N Engl J Med, 2005.
352(13):
p. 1293-304.
3. Karha, J., et al., Lack of effect of enteric coating on aspirin-induced
inhibition of platelet aggregation in healthy volunteers. Am Heart J,
2006.
151(5): p. 976 e7-11.
Competing interests:
None declared
Competing interests: No competing interests
We read with interest the recent article of Gang and colleagues who
concluded that the long term use of low dose aspirin does not provide
overall benefits for cognition among generally healthy women aged 65 or
more (1). Regardless of its preventive and therapeutic efficacy in chronic
inflammatory pathologies and cardiovascular disease, aspirin is widely
used in the general population to reduce pain and inflammation with little
awareness on safety, tolerability, risks and potential adverse
complications. Aspirin it is not free from side effects, including kidney
and gastric injury. The marked inhibition of the platelet function is also
associated with important bleeding complications due to irreversible
acetylation of the platelet cyclooxygenase (COX), especially the
constitutive isoform COX-1 (2). There is evidence that aspirin is commonly
abused, when administered to treat banal pathologies that would not
require a drastic therapeutic intervention, minor migraine or tolerable
muscle-skeletal pain among others (2). In such cases, the individual
benefit/risk ratio should be carefully determined before administration
and the brilliant conclusions of Gang and colleagues thoughtfully support
our hypothesis. As recently highlighted by the Third Canadian Consensus
Conference, that recommended to routinely reassess patients' risk before
prescribing NSAIDs regardless of the individual lifestyle (3), aspirin
must not be abused and, especially, should not be administered when no
definitive proofs on benefits for a given pathology are demonstrated.
Accordingly, major commitment should be placed in modifying the
physicians' appropriate prescribing of easily accessible, over-the-counter
drugs, including aspirin.
References
1. Kang JH, Cook N, Manson J, Buring JE, Grodstein F. Low dose
aspirin and cognitive function in the women's health study cognitive
cohort. BMJ 2007; 0: bmj.39166.597836.BEv1
2. Lippi G, Franchini M, Guidi GC, Kean WF. Non-steroidal anti-
inflammatory drugs in athletes. Br J Sports Med 2006;40:661-2.
3. Tannenbaum H, Bombardier C, Davis P, Russell AS; Third Canadian
Consensus Conference Group. An evidence-based approach to prescribing
nonsteroidal antiinflammatory drugs. Third Canadian Consensus Conference.
J Rheumatol 2006;33:140-57.
Competing interests:
None declared
Competing interests: No competing interests
This study (1) represents an interesting contribution to the
continuing debate about the usefulness (or lack thereof) of aspirin and
non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention and
treatment of cognitive decline in later life. The authors acknowledge the
dose of aspirin used was insufficient to test a putative anti-inflammatory
mechanism of action and would therefore only be likely to detect possible
benefit resulting from platelet inhibition; an additional major
consideration mentioned only briefly in their discussion is that of the
timing of the relationship between either platelet aggregation or
inflammatory mechanisms to the onset and progression of cognitive decline.
Many of the observational studies of NSAIDs reporting associations between
use of these drugs and reduced rates of cognitive decline (2,3,4,5)
included subjects with long periods of exposure to these drugs in mid-
adult life. This is increasingly recognised as the period during which
neurodegenerative processes may become established (6). The potential of
these agents for primary prevention of cognitive decline will remain
unknown until we have seen the results of intervention studies involving
younger adults.
1. Kang JH, Cook N, Manson J, Buring JE and Grodstein F. Low dose
aspirin and cognitive function in the women's health study cognitive
cohort. BMJ, Doi:10.1136/bmj.39166.597836.BE (published 27 April 2007)
2. Sturmer T Glynn RJ Field TS Taylor JO Hennekens CH. Aspirin use and
cognitive function in the elderly. Am J Epidemiol 1996.143; 7: 683-691
3. Stewart WF Kawas C Corrada M Metter EJ. Risk of Alzheimer's disease and
duration of NSAID use. Neurology 1997. 48;3:626-32
4.Bas A, Veld MD, Ruitenberg A, Hofman A, Launer LJ, Van Duijn CM,
Stijenen T, Breteler MMB and Stricker BHC. Nonsteroidal anti-inflammatory
drugs and the risk of Alzheimer's disease. NEJM 2001; 345; 21:1515-20
5. Jonker C, Comijs HC, Smit JH. Does aspirin or other NSAIDs reduce the
risk of cognitive decline in elderly persons? Results from a
population-based study. Neurobiol Aging 2003;24:583-8.
6. Braak E, Griffing K, Arai K, Bohl J, Bratzke H, Braak H. Neuropathology
of Alzheimer's disease: what is new since A. Alzheimer? Eur Arch
Psychiatry Clin Neurosci 1999;249(Suppl 3):14-22.
Competing interests:
None declared
Competing interests: No competing interests
I read with interest the paper JH Gang and colleagues on the
inability of aspirin (ASA)100 mg every other day to impede cognitive
decline in elderly women. In my opinion, results of this and other primary
prevention studies employing ASA are in line with the fact that a major
pathogenic mechanism of mental impairment in the elderly, i.e.
cardioembolism due to AF, is prevented by OA and not by antiplatelet
drugs. In patients with AF small fibrin-rich thrombi, resembling those
formed in the venous circulation, may in fact migrate from left appendage
to the brain causing silent ischemia by occluding small brain penetrating
arteries, which leads to cognitive impairment and dementia. In this large
cohort study, patients with AF and those among them treated with OA may
have been equally distrubuted in the two arms. In the same way new onset
AF, an age-related rythm disturbance may have fallen equally in the two
groups. Thus what the study may in part measure is the aspirin-independent
mental decline occurring in patients with AF and silent brain embolism.
Competing interests:
None declared
Competing interests: No competing interests
cognitive function and diabetes
Reading your editorial on decline in cognitive function and the use
of low dose
aspirin it struck me that one seldom sees any correlation between
cognitive
decline and diabetes.
Type 2 diabetes,in particular ,affects the most common age group for
cognitive
decline. It is also a disease which produces many of its major effects by
small
vessel arterial decline and ultimately blockage. Surely one would expect
the
cerebral circulation to suffer in the same way as the rest of the body.
The
presence or absence of such an effect would be an indicator as to the
mechanism of cognitive failure.
In primary care in the UK we have a very large database on diabetes
and its
effects. This is held in an anonymous form by the National Health Service
[ NHS]
as part of its Quality Management and Analysis System [QMAS] data. Can
this
not be used to investigate the possibilty of an effect ? If more questions
need to
be asked why not include them in the required dataset [ perhaps removing
one
or two others so as to relieve the burden on primary care].
Competing interests:
None declared
Competing interests: No competing interests