Effects of blood pressure and lipid lowering on cognition

Abstract

ObjectiveTo assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk.MethodsThe Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 × 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were ≥70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end.ResultsCognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD ±3.5 years); 59% were women; 45% had hypertension; and 24% had ≥12 years of education. The mean difference in change in DSST scores was −0.91 (95% confidence interval [CI] −2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, −0.54 (95% CI −1.88 to 0.80) for rosuvastatin compared with placebo, and −1.43 (95% CI −3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures.ConclusionsLong-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people.ClinicalTrials.gov identifierNCT00468923.Classification of evidenceThis study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.

<p>Effect of Switching from Low-Dose Simvastatin to High-Dose Atorvastatin on Glucose Homeostasis and Cognitive Function in Type 2 Diabetes</p>

“…[18][19][20] However, post hoc analysis from the HOPE-3 study found no significant deterioration in neurocognitive function with rosuvastatin treatment, as assessed by MoCA and TMT. 37 A meta-analysis by Ott et al 38 did not find a significant difference in the incidence of dementia, confusion, or other adverse cognitive events between the statin and placebo groups among patients with normal cognition at baseline. Moreover, a crosssectional study in coronary artery disease patients found high-dose statin to be associated with better cognition than low-dose statin, as assessed by MoCA and TMT.…”

Cerebrovascular risk factors impact frontoparietal network integrity and executive function in healthy ageing

“…However, most investigations have assessed the presence of vascular risk factors or risk factor modification and related these to global cognition, using either MMSE or composite cognitive scores 15 – 19 . One recent study has reported a benefit of statin and BP-lowering medication using a more sensitive digit-symbol substitution score in healthy people without any known cardiovascular disease 20 . Overall, however, to the best of our knowledge there has been no clear demonstration of a parametric effect of risk factors (e.g., BP level, rather than simply presence or absence of hypertension or BP-lowering treatment) associated with systematic differences in cognitive performance.…”

Primary Prevention Statins in Older Adults: Personalized Care for a Heterogeneous Population

“…The ACC/AHA reviewed statin safety data and addressed it in the 2013 cholesterol guideline and showed no randomized controlled trial evidence of statin‐associated cognitive change or risk of dementia . Recent data from the HOPE‐3 randomized controlled trial in a population with a mean age 74 years showed that candesartan with hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in this study of older adults . Additionally, autopsy studies show no significant difference in Alzheimer's disease onset or in burden of plaques and tangles on autopsy study in those on a statin, compared with those not on statin therapy …”

“…42 Recent data from the HOPE-3 randomized controlled trial in a population with a mean age 74 years showed that candesartan with hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in this study of older adults. 43 Additionally, autopsy studies show no significant difference in Alzheimer's disease onset or in burden of plaques and tangles on autopsy study in those on a statin, compared with those not on statin therapy. 44,45 A CAC score could be performed in the case of B.H., just as it was in case 1.…”