Justine E F Moonen1, Jessica C Foster-Dingley1, Wouter de Ruijter2, Jeroen van der Grond3, Anne Suzanne Bertens4, Mark A van Buchem3, Jacobijn Gussekloo2, Huub A Middelkoop5, Marieke J H Wermer6, Rudi G J Westendorp7, Anton J M de Craen8, Roos C van der Mast9. 1. Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands. 2. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands. 3. Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands. 4. Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands4Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands. 5. Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands6Section of Health, Medical and Neuropsychology, Department of Psychology, Leiden University, Leiden, the Netherlands. 6. Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. 7. Leyden Academy on Vitality and Aging, Leiden University Medical Center, Leiden, the Netherlands8Center for Healthy Aging, Department of Public Health, University of Copenhagen, Cophenhagen, Denmark. 8. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands. 9. Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands9Department of Psychiatry, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.
Abstract
IMPORTANCE: Observational studies indicate that lower blood pressure (BP) increases risk for cognitive decline in elderly individuals. Older persons are at risk for impaired cerebral autoregulation; lowering their BP may compromise cerebral blood flow and cognitive function. OBJECTIVE: To assess whether discontinuation of antihypertensive treatment in older persons with mild cognitive deficits improves cognitive, psychological, and general daily functioning. DESIGN, SETTING, AND PARTICIPANTS: A community-based randomized clinical trial with a blinded outcome assessment at the 16-week follow-up was performed at 128 general practices in the Netherlands. A total of 385 participants 75 years or older with mild cognitive deficits (Mini-Mental State Examination score, 21-27) without serious cardiovascular disease who received antihypertensive treatment were enrolled in the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden from June 26, 2011, through August 23, 2013 (follow-up, December 16, 2013). Intention-to-treat analyses were performed from January 20 through April 11, 2014. INTERVENTIONS:Discontinuation (n=199) vs continuation (n=186) of antihypertensive treatment (allocation ratio, 1:1). MAIN OUTCOMES AND MEASURES: Change in the overall cognition compound score. Secondary outcomes included changes in scores on cognitive domains, the Geriatric Depression Scale-15, Apathy Scale, Groningen Activity Restriction Scale (functional status), and Cantril Ladder (quality of life). RESULTS: Compared with 176 participants undergoing analysis in the control (continuation) group, 180 in the intervention (discontinuation) group had a greater increase (95% CI) in systolic BP (difference, 7.36 [3.02 to 11.69] mm Hg; P=.001) and diastolic BP (difference, 2.63 [0.34 to 4.93] mm Hg; P=.03). The intervention group did not differ from the control group in change (95% CI) in overall cognition compound score (0.01 [-0.14 to 0.16] vs -0.01 [-0.16 to 0.14]; difference, 0.02 [-0.19 to 0.23]; P=.84). The intervention and control groups did not differ significantly in secondary outcomes, including differences (95% CIs) in change in compound scores of the 3 cognitive domains (executive function, -0.07 [-0.29 to 0.15; P=.52], memory, 0.08 [-0.12 to 0.29; P=.43], and psychomotor speed, -0.85 [-1.72 to 0.02; P=.06]), symptoms of apathy (0.17 [-0.65 to 0.99; P=.68]) and depression (0.14 [-0.20 to 0.48; P=.41]), functional status (-0.72 [-1.52 to 0.09; P=.08]), and quality-of-life score (-0.09 [-0.34 to 0.16; P=.46]). Adverse events were equally distributed. CONCLUSIONS AND RELEVANCE: In older persons with mild cognitive deficits, discontinuation ofantihypertensive treatment did not improve cognitive, psychological, or general daily functioning at the 16-week follow-up. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2829.
RCT Entities:
IMPORTANCE: Observational studies indicate that lower blood pressure (BP) increases risk for cognitive decline in elderly individuals. Older persons are at risk for impaired cerebral autoregulation; lowering their BP may compromise cerebral blood flow and cognitive function. OBJECTIVE: To assess whether discontinuation of antihypertensive treatment in older persons with mild cognitive deficits improves cognitive, psychological, and general daily functioning. DESIGN, SETTING, AND PARTICIPANTS: A community-based randomized clinical trial with a blinded outcome assessment at the 16-week follow-up was performed at 128 general practices in the Netherlands. A total of 385 participants 75 years or older with mild cognitive deficits (Mini-Mental State Examination score, 21-27) without serious cardiovascular disease who received antihypertensive treatment were enrolled in the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden from June 26, 2011, through August 23, 2013 (follow-up, December 16, 2013). Intention-to-treat analyses were performed from January 20 through April 11, 2014. INTERVENTIONS: Discontinuation (n=199) vs continuation (n=186) of antihypertensive treatment (allocation ratio, 1:1). MAIN OUTCOMES AND MEASURES: Change in the overall cognition compound score. Secondary outcomes included changes in scores on cognitive domains, the Geriatric Depression Scale-15, Apathy Scale, Groningen Activity Restriction Scale (functional status), and Cantril Ladder (quality of life). RESULTS: Compared with 176 participants undergoing analysis in the control (continuation) group, 180 in the intervention (discontinuation) group had a greater increase (95% CI) in systolic BP (difference, 7.36 [3.02 to 11.69] mm Hg; P=.001) and diastolic BP (difference, 2.63 [0.34 to 4.93] mm Hg; P=.03). The intervention group did not differ from the control group in change (95% CI) in overall cognition compound score (0.01 [-0.14 to 0.16] vs -0.01 [-0.16 to 0.14]; difference, 0.02 [-0.19 to 0.23]; P=.84). The intervention and control groups did not differ significantly in secondary outcomes, including differences (95% CIs) in change in compound scores of the 3 cognitive domains (executive function, -0.07 [-0.29 to 0.15; P=.52], memory, 0.08 [-0.12 to 0.29; P=.43], and psychomotor speed, -0.85 [-1.72 to 0.02; P=.06]), symptoms of apathy (0.17 [-0.65 to 0.99; P=.68]) and depression (0.14 [-0.20 to 0.48; P=.41]), functional status (-0.72 [-1.52 to 0.09; P=.08]), and quality-of-life score (-0.09 [-0.34 to 0.16; P=.46]). Adverse events were equally distributed. CONCLUSIONS AND RELEVANCE: In older persons with mild cognitive deficits, discontinuation of antihypertensive treatment did not improve cognitive, psychological, or general daily functioning at the 16-week follow-up. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2829.
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