Can antihypertensive agents reduce dementia risk without affecting blood pressure?
LalitKalra, Professor of Stroke Medicine, King's College Londonlalit.kalra@kcl.ac.uk
Submitted August 16, 2013
Yasar et al. based their article [1] on a secondary analysis of incidental data collected during a published clinical trial on the use of ginkgo to reduce the incidence of dementia. [2] The authors found that diuretics ARB and ACE-I reduced the risk of AD independent of--or in addition to--mean systolic blood pressure in participants with normal cognition. However, they also found that only diuretic use was associated with reduced risk of AD in participants with MCI. These findings are counterintuitive and conflict with existing literature.
Recent publications from large observational and randomized controlled studies show a relationship between blood pressure, white matter disease, and interactions with AD in dementia progression. [2,3] It would be difficult to find a biological explanation for the "dementia reducing" effect of these agents independent of initial blood pressure or blood pressure reduction. Furthermore, the biological plausibility of these agents having a greater effect in people with normal cognition compared to those with MCI (who are known to progress faster with higher blood pressure levels) is still unclear.
A major problem with post hoc analyses is that these data were collected without a firm "a priori" hypothesis, which introduces a significant element of bias. Further bias is added by the multiple statistical manipulations of several data items, which are likely to produce erroneous results purely by chance in 1 out of every 20 calculations. In addition, there are several methodological flaws. The main flaw is the lack of assessment of blood pressure at the beginning of the study and no formalized protocol to regularly monitor blood pressure control. Hence, an effect of these agents that is independent of the levels of blood pressure during the period of observation simply cannot be established.
1. Yasar S, Xia J, Yao W, et al. for the Ginkgo Evaluation of Memory (GEM) Study Investigators. Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study Neurology 2013; 0: 1331823-101212001
2. Godin O, Tzourio C, Maillard P, Mazoyer B, Dufouil C. Antihypertensive treatment and change in blood pressure are associated with the progression of white matter lesion volumes: the Three-City (3C)- Dijon Magnetic Resonance Imaging Study. Circulation 2011;123:266-273.
3. Soros P, Whitehead S, Spence JD, Hachinski V. Antihypertensive treatment can prevent stroke and cognitive decline. Nat Rev Neurol 2013;9:174-178.
For disclosures, contact the editorial office at journal@neurology.org.
Yasar et al. based their article [1] on a secondary analysis of incidental data collected during a published clinical trial on the use of ginkgo to reduce the incidence of dementia. [2] The authors found that diuretics ARB and ACE-I reduced the risk of AD independent of--or in addition to--mean systolic blood pressure in participants with normal cognition. However, they also found that only diuretic use was associated with reduced risk of AD in participants with MCI. These findings are counterintuitive and conflict with existing literature.
Recent publications from large observational and randomized controlled studies show a relationship between blood pressure, white matter disease, and interactions with AD in dementia progression. [2,3] It would be difficult to find a biological explanation for the "dementia reducing" effect of these agents independent of initial blood pressure or blood pressure reduction. Furthermore, the biological plausibility of these agents having a greater effect in people with normal cognition compared to those with MCI (who are known to progress faster with higher blood pressure levels) is still unclear.
A major problem with post hoc analyses is that these data were collected without a firm "a priori" hypothesis, which introduces a significant element of bias. Further bias is added by the multiple statistical manipulations of several data items, which are likely to produce erroneous results purely by chance in 1 out of every 20 calculations. In addition, there are several methodological flaws. The main flaw is the lack of assessment of blood pressure at the beginning of the study and no formalized protocol to regularly monitor blood pressure control. Hence, an effect of these agents that is independent of the levels of blood pressure during the period of observation simply cannot be established.
1. Yasar S, Xia J, Yao W, et al. for the Ginkgo Evaluation of Memory (GEM) Study Investigators. Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study Neurology 2013; 0: 1331823-101212001
2. Godin O, Tzourio C, Maillard P, Mazoyer B, Dufouil C. Antihypertensive treatment and change in blood pressure are associated with the progression of white matter lesion volumes: the Three-City (3C)- Dijon Magnetic Resonance Imaging Study. Circulation 2011;123:266-273.
3. Soros P, Whitehead S, Spence JD, Hachinski V. Antihypertensive treatment can prevent stroke and cognitive decline. Nat Rev Neurol 2013;9:174-178.
For disclosures, contact the editorial office at journal@neurology.org.