Effect of Discontinuation of Antihypertensive Treatment in Elderly People on Cognitive Functioning-the DANTE Study Leiden: A Randomized Clinical Trial

TY - JOUR

T1 - Effect of Discontinuation of Antihypertensive Treatment in Elderly People on Cognitive Functioning-the DANTE Study Leiden

T2 - A Randomized Clinical Trial

AU - Moonen, Justine E F

AU - Foster-Dingley, Jessica C

AU - de Ruijter, Wouter

AU - van der Grond, Jeroen

AU - Bertens, Anne Suzanne

AU - van Buchem, Mark A

AU - Gussekloo, Jacobijn

AU - Middelkoop, Huub A

AU - Wermer, Marieke J H

AU - Westendorp, Rudi G J

AU - de Craen, Anton J M

AU - van der Mast, Roos C

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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 BPmay compromise cerebral blood flowand 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, Andparticipants: Acommunity-based randomized clinical trial with a blinded outcome assessment at the 16-week follow-upwas 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 diseasewhoreceived antihypertensive treatmentwere 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 analyseswere performed from January 20through 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]mmHg; P = .001) and diastolic BP (difference, 2.63 [0.34 to 4.93]mmHg; 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.

AB - 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 BPmay compromise cerebral blood flowand 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, Andparticipants: Acommunity-based randomized clinical trial with a blinded outcome assessment at the 16-week follow-upwas 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 diseasewhoreceived antihypertensive treatmentwere 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 analyseswere performed from January 20through 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]mmHg; P = .001) and diastolic BP (difference, 2.63 [0.34 to 4.93]mmHg; 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.

U2 - 10.1001/jamainternmed.2015.4103

DO - 10.1001/jamainternmed.2015.4103

M3 - Journal article

C2 - 26301603

SN - 2168-6106

VL - 175

SP - 1622

EP - 1630

JO - JAMA Internal Medicine

JF - JAMA Internal Medicine

IS - 10

ER -