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Review
. 2018 May 7;31(6):631-642.
doi: 10.1093/ajh/hpy033.

Clinical Trials of Blood Pressure Lowering and Antihypertensive Medication: Is Cognitive Measurement State-of-the-Art?

Merrill F Elias  1 , Rachael V Torres  2 , Adam Davey  3
Affiliations
Review

Clinical Trials of Blood Pressure Lowering and Antihypertensive Medication: Is Cognitive Measurement State-of-the-Art?

Merrill F Elias et al. Am J Hypertens. .

Abstract

Randomized controlled trials of blood pressure (BP) lowering and antihypertensive medication use on cognitive outcomes have often been disappointing, reporting mixed findings and small effect sizes. We evaluate the extent to which cognitive assessment protocols used in these trials approach state-of-the-art. Overall, we find that a primary focus on cognition and the systematic selection of cognitive outcomes across trials take a backseat to other trial goals. Twelve trials investigating change in cognitive functioning were examined and none met criteria for state-of-the-art assessment, including use of at least 4 tests indexing 2 cognitive domains. Four trials investigating incident dementia were also examined. Each trial used state-of-the-art diagnostic criteria to assess dementia, although follow-up periods were relatively short, with only 2 trials lasting for at least 3 years. Weaknesses in each trial may act to obscure or weaken the positive effects of BP lowering on cognitive functioning. Improving trial designs in terms of cognitive outcomes selected and length of follow-up periods employed could lead to more promising findings. We offer logical steps to achieve state-of-the-art assessment protocols, with examples, in hopes of improving future trials.

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Figures

Figure 1.
Figure 1.
Model of the clinical trajectory of Alzheimer’s disease (AD). Reused from Sperling et al. with permission.
Figure 2.
Figure 2.
Spearman’s general factor model.
Figure 3.
Figure 3.
Thurstone’s multiple factor model.
Figure 4.
Figure 4.
Wechsler Adult Intelligence Scale hierarchy of cognitive domains, abilities and tests.
See this image and copyright information in PMC

References

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    1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7:280–292. - PMC - PubMed
    1. Elias MF, Goodell AL, Robbins MA. Blood pressure and cognitive functioning: longitudinal studies, treatment and new directions. In Waldstein S, Elias MF (eds), Neuropsychology of Cardiovascular Disease, 2nd edn Taylor & Francis: New York, NY, 2015.
    1. Elias MF, Goodell AL, Dore GA. Hypertension and cognitive functioning: a perspective in historical context. Hypertension 2012; 60:260–268. - PubMed
    1. Elias MF, Wolf PA, D’Agostino RB, Cobb J, White LR. Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. Am J Epidemiol 1993; 138:353–364. - PubMed

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