Age Ageing. 2026 Jan 3;55(1):afag005. doi: 10.1093/ageing/afag005.
ABSTRACT
BACKGROUND: Orthostatic hypotension (OH) increases the risk of dementia. Although intensive blood pressure (BP) lowering may have cognitive benefits regardless of baseline OH status, its effects in participants who develop OH during intervention remain unknown.
METHODS: Participants of the Systolic Blood Pressure Intervention Trial (SPRINT) were randomised to either intensive treatment (systolic BP target <120 mmHg) or standard treatment (systolic BP target <140 mmHg). This post hoc analysis defined new-onset OH as a systolic BP reduction ≥20 mmHg and/or a diastolic BP reduction ≥10 mmHg from a seated to a standing position at any follow-up visit during intervention. The primary outcome was probable dementia. Other outcomes included mild cognitive impairment (MCI), and a composite of probable dementia or MCI.
RESULTS: Amongst 7911 participants without OH at baseline (representing 84.5% of randomised participants in SPRINT; mean age, 67.7 years; 34.7% women), 1264 (16.0%) developed new-onset OH during intervention. Intensive treatment was associated with a lower risk of probable dementia (HR, 0.76; 95% CI, 0.58 to 0.98) amongst participants without new-onset OH, but with a higher risk (HR, 2.39; 95% CI, 1.33 to 4.32) amongst participants with new-onset OH. No significant association was observed between intensive treatment and MCI, or the composite outcome in participants with new-onset OH.
CONCLUSIONS: The occurrence of OH requires close monitoring, with caution for potential cognitive adverse effects during ongoing intensive BP-lowering treatment. Validation of current findings in studies with justified methodological designs is warranted.
REGISTRATION: URL: ClinicalTrials.gov; Unique Identifier: NCT01206062.
PMID:41609319 | DOI:10.1093/ageing/afag005