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SPRINT MIND

Q: What were the key findings of the SPRINT MIND trial?

In hypertensive adults without diabetes or prior stroke, intensive blood pressure control (<120 mmHg SBP) did NOT significantly reduce probable dementia (HR 0.83; 95% CI 0.67-1.04) but did significantly reduce mild cognitive impairment (HR 0.81; 95% CI 0.69-0.95) and the composite of MCI or probable dementia (HR 0.85; p=0.01) over median 5.1 years. These findings support intensive BP control as a modifiable strategy to prevent early cognitive decline.

Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial

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Year of Publication: 2019

Authors: The SPRINT MIND Investigators for the SPRINT Research Group

Journal: JAMA

Citation: JAMA 2019;321(6):553-561

Link: https://doi.org/10.1001/jama.2018.21442

PDF: https://jamanetwork.com/journals/jama/fullarticle/2723256

Clinical Question

Does intensive blood pressure control (<120 mmHg SBP) reduce the risk of dementia or mild cognitive impairment compared with standard control (<140 mmHg) in hypertensive adults without diabetes or stroke?

Bottom Line

In hypertensive adults without diabetes or prior stroke, intensive blood pressure control (<120 mmHg SBP) did NOT significantly reduce probable dementia (HR 0.83; 95% CI 0.67-1.04) but did significantly reduce mild cognitive impairment (HR 0.81; 95% CI 0.69-0.95) and the composite of MCI or probable dementia (HR 0.85; p=0.01) over median 5.1 years. These findings support intensive BP control as a modifiable strategy to prevent early cognitive decline.

        Major Points
        Randomized controlled trial of 9361 hypertensive adults ≥50 years
Enrolled at 102 sites in US and Puerto Rico
Randomized to intensive BP treatment (target <120 mmHg SBP) or standard treatment (target <140 mmHg)
SPRINT trial was stopped early in August 2015 for primary cardiovascular benefit and all-cause mortality
Cognitive outcomes follow-up continued through July 2018
8563 of 9361 (91.5%) completed ≥1 cognitive assessment
Median intervention period: 3.34 years; median total follow-up: 5.11 years
Primary cognitive outcome: adjudicated probable dementia
Probable dementia: 149 (intensive) vs 176 (standard); 7.2 vs 8.6 per 1000 person-years
HR for probable dementia: 0.83 (95% CI 0.67-1.04) — NOT statistically significant
MCI (secondary): significantly reduced; HR 0.81 (95% CI 0.69-0.95)
Composite MCI or probable dementia (secondary): significantly reduced; HR 0.85 (95% CI 0.74-0.97); p=0.01
Early trial termination likely limited power for dementia-alone endpoint
Baseline mean age 67.9 years; 35.6% women
Hypotension, syncope, electrolyte abnormalities, and acute kidney injury more common in intensive arm
No excess in injurious falls
First large randomized trial to show cognitive impairment prevention from BP control — shifted hypertension guidelines toward lower targets for cognitive protection in addition to CV protection

      

Design

Study Type: Randomized controlled multicenter trial (ancillary cognitive study of SPRINT)

Randomization: 1

Blinding: Open-label treatment; blinded adjudication of cognitive outcomes

Enrollment Period: November 2010 onwards

Follow-up Duration: Median 5.11 years (SPRINT main trial stopped early Aug 2015)

Centers: 102

Countries: USA, Puerto Rico

Sample Size: 9361

Analyzed: 8563

Analysis: Intention-to-treat; Cox proportional hazards

Inclusion Criteria

Age ≥50 years
Hypertension: SBP 130-180 mmHg on 0-4 antihypertensives
≥1 cardiovascular risk factor
Estimated CKD risk, atherosclerotic CV disease, Framingham ≥15% 10-y risk, age ≥75

Exclusion Criteria

Diabetes mellitus (separate trial: ACCORD)
Prior stroke (concern for cerebral ischemia with BP lowering)
Severe heart failure
Severe CKD (eGFR <20)
Life expectancy <3 years or dementia at baseline

Baseline Characteristics

Characteristic	Control	Active
N	4683	4678
Age mean	67.9	67.9
Women	35.6%	35.6%
Baseline SBP	~140	~140

Arms

Field	Control	Intensive BP control
N	4683	4678
Intervention	Antihypertensive therapy targeting SBP <140 mmHg per guideline	Antihypertensive therapy targeting SBP <120 mmHg per guideline
Duration	Median intervention 3.34 years	Median intervention 3.34 years

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Adjudicated probable dementia during follow-up	Primary	176 events, 8.6 per 1000 person-years	149 events, 7.2 per 1000 person-years	0.83	Not statistically significant
Mild cognitive impairment	Secondary	More common with standard	Significantly reduced with intensive	HR 0.81 (95% CI 0.69-0.95)	Statistically significant
Composite MCI or probable dementia	Secondary	Higher event rate	Lower event rate with intensive	HR 0.85 (95% CI 0.74-0.97)	p=0.01
Composite cognitive test score change (exploratory)	Secondary	Baseline decline	Similar decline		Not significantly different
All-cause mortality	Secondary	Higher	Lower in intensive arm (from main SPRINT)		Significant in main SPRINT
Hypotension	Adverse	2.4%	3.4%		Higher with intensive
Syncope	Adverse	2.4%	3.4%		Higher with intensive
Electrolyte abnormality	Adverse	2.8%	3.8%		Higher with intensive
Acute kidney injury	Adverse	2.6%	4.4%		Higher with intensive
Injurious fall	Adverse	7.1%	7.1%		No difference
Orthostatic hypotension (postural dizziness)	Adverse	Common	Common; somewhat higher		Modest increase
Serious adverse events	Adverse	Comparable	Comparable overall		Mostly balanced

Subgroup Analysis

Effect on MCI and composite MCI-or-dementia was consistent across subgroups by age, sex, baseline SBP, CKD status, and prior cardiovascular disease. The statistically significant benefit on MCI but not dementia alone is consistent with either limited follow-up time (dementia requires longer latency) or possibly earlier cognitive changes being more responsive to BP modulation.

Criticisms

Primary dementia endpoint did not reach statistical significance — early termination reduced follow-up and power
Excluded diabetics and prior stroke patients — limits generalizability to these high-risk groups
Intensive BP control requires multiple drugs and monitoring — real-world implementation may differ
More AEs (hypotension, AKI) require clinical vigilance
No specific drug regimen mandated — heterogeneity in actual therapeutic exposure
Cognitive assessment differed across participants based on cognitive screening results

Funding

NIH / NHLBI / NIA / NINDS

Based on: SPRINT MIND (JAMA, 2019)

Authors: The SPRINT MIND Investigators for the SPRINT Research Group

Citation: JAMA 2019;321(6):553-561

Content summarized and formatted by NeuroTrials.ai.

SPRINT MIND

(2019)

Objective

Intensive (<120 mmHg) vs standard (<140 mmHg) systolic blood pressure control — to evaluate effect on incident probable dementia and mild cognitive impairment in hypertensive adults.

Study Summary

• Intensive blood pressure control to SBP <120 mmHg did NOT significantly reduce probable dementia alone (HR 0.83; 95% CI 0.67-1.04).
• Intensive control SIGNIFICANTLY reduced mild cognitive impairment by 19% (HR 0.81; 95% CI 0.69-0.95).
• The composite of MCI or probable dementia was significantly reduced by 15% (HR 0.85; p=0.01).
• SPRINT was terminated early for benefit on cardiovascular outcomes, limiting follow-up duration and statistical power for dementia.
• Intensive group had higher rates of hypotension, electrolyte abnormalities, and acute kidney injury.
• First large randomized trial to show intensive BP control can reduce early cognitive impairment, supporting BP management as a modifiable dementia risk factor.

Intervention

Intensive BP treatment targeting SBP <120 mmHg vs standard treatment targeting SBP <140 mmHg. Drugs were chosen per guideline; no specific regimen mandated.

Inclusion Criteria

Adults ≥50 years with hypertension (SBP 130-180 mmHg on 0-4 meds) and ≥1 cardiovascular risk factor. Excluded: diabetes, prior stroke, severe CHF.

Study Design

Arms: Intensive (SBP <120 mmHg) vs Standard (SBP <140 mmHg)

Patients per Arm: Intensive 4678; Standard 4683 (N=9361)

Outcome

• Primary cognitive outcome: Probable dementia — 7.2 vs 8.6 per 1000 person-years (intensive vs standard); HR 0.83 (95% CI 0.67-1.04); not statistically significant
• Mild cognitive impairment: HR 0.81 (95% CI 0.69-0.95); SIGNIFICANT
• Composite MCI or probable dementia: HR 0.85 (95% CI 0.74-0.97); p=0.01; SIGNIFICANT
• Median intervention period 3.34 years; median total follow-up 5.11 years (trial stopped early for CV benefit)
• AEs: hypotension, syncope, electrolyte abnormalities, and acute kidney injury more common in intensive arm
• No increased fall-related injury

Clinical Question

Does intensive BP control (SBP <120 mmHg) prevent incident dementia or mild cognitive impairment in hypertensive adults?

Bottom Line

Major Points

Randomized controlled trial of 9361 hypertensive adults ≥50 years
Enrolled at 102 sites in US and Puerto Rico
Randomized to intensive BP treatment (target <120 mmHg SBP) or standard treatment (target <140 mmHg)
SPRINT trial was stopped early in August 2015 for primary cardiovascular benefit and all-cause mortality
Cognitive outcomes follow-up continued through July 2018
8563 of 9361 (91.5%) completed ≥1 cognitive assessment
Median intervention period: 3.34 years; median total follow-up: 5.11 years
Primary cognitive outcome: adjudicated probable dementia
Probable dementia: 149 (intensive) vs 176 (standard); 7.2 vs 8.6 per 1000 person-years
HR for probable dementia: 0.83 (95% CI 0.67-1.04) — NOT statistically significant
MCI (secondary): significantly reduced; HR 0.81 (95% CI 0.69-0.95)
Composite MCI or probable dementia (secondary): significantly reduced; HR 0.85 (95% CI 0.74-0.97); p=0.01
Early trial termination likely limited power for dementia-alone endpoint
Baseline mean age 67.9 years; 35.6% women
Hypotension, syncope, electrolyte abnormalities, and acute kidney injury more common in intensive arm
No excess in injurious falls
First large randomized trial to show cognitive impairment prevention from BP control — shifted hypertension guidelines toward lower targets for cognitive protection in addition to CV protection

Study Design

Study Type: Randomized controlled multicenter trial (ancillary cognitive study of SPRINT)
Randomization: Yes
Blinding: Open-label treatment; blinded adjudication of cognitive outcomes
Sample Size: 9361
Follow-up: Median 5.11 years (SPRINT main trial stopped early Aug 2015)
Centers: 102
Countries: USA, Puerto Rico

Primary Outcome

Definition: Adjudicated probable dementia during follow-up

Control	Intervention	HR/OR	P-value
176 events, 8.6 per 1000 person-years	149 events, 7.2 per 1000 person-years	0.83 (0.67-1.04)	Not statistically significant

Limitations & Criticisms

Primary dementia endpoint did not reach statistical significance — early termination reduced follow-up and power
Excluded diabetics and prior stroke patients — limits generalizability to these high-risk groups
Intensive BP control requires multiple drugs and monitoring — real-world implementation may differ
More AEs (hypotension, AKI) require clinical vigilance
No specific drug regimen mandated — heterogeneity in actual therapeutic exposure
Cognitive assessment differed across participants based on cognitive screening results

Citation

JAMA 2019;321(6):553-561

View Original Publication →

SPRINT MIND

Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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