Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study.
Level 3 - non-randomized controlled study
Prospective longitudinal birth cohort follow-up study
PubMed 31444142 · doi:10.1016/S1474-4422(19)30228-5
What was done
Researchers evaluated participants from Insight 46, a neuroscience substudy of the 1946 British birth cohort (MRC National Survey of Health and Development). Blood pressure (BP) was measured at ages 36, 43, 53, 60–64, and 69 years, alongside calculated BP changes between intervals. At ages 69–71 years, 465 dementia-free participants (51% men, mean age 70.7 years) underwent volumetric MRI, florbetapir amyloid-PET, and cognitive assessment using the Preclinical Alzheimer Cognitive Composite (PACC). Adjusted regression models examined associations between BP trajectories and late-life white matter hyperintensity volume (WMHV), whole-brain and hippocampal volumes, amyloid-β positivity, and PACC scores.
What was found
Higher systolic BP (SBP) and diastolic BP (DBP) at age 53, as well as greater increases between ages 43 and 53, were associated with higher WMHV at ages 69–71: mean WMHV increased by 7% per 10 mm Hg higher SBP (95% CI 1 to 14, p=0.024), 15% per 10 mm Hg higher DBP (95% CI 4 to 27, p=0.0057), 15% per 1 SD increase in SBP change (95% CI 3 to 29, p=0.012), and 15% per 1 SD increase in DBP change (95% CI 3 to 30, p=0.017). Higher DBP at age 43 was associated with smaller whole-brain volume (-6.9 mL per 10 mm Hg, 95% CI -11.9 to -1.9, p=0.0068), as was greater DBP increase between ages 36 and 43 (-6.5 mL per 1 SD, 95% CI -11.1 to -1.9, p=0.0054). Greater SBP increase between ages 36 and 43 was linked to smaller hippocampal volume (-0.03 mL per 1 SD, 95% CI -0.06 to -0.001, p=0.043). Neither absolute BP nor BP change predicted amyloid-β positivity (18% of cohort) or PACC scores at ages 69–71.
Why it matters
This study pinpoints early adulthood to midlife (ages 36–53) as a critical window where rising blood pressure inflicts cerebrovascular damage and brain volume loss by age 70. It suggests midlife hypertension affects late-life brain structure primarily via vascular pathology and atrophy rather than amyloid-β accumulation.
Limits
The study is observational and restricted to a single mainland British birth cohort born during one week in 1946, limiting ethnic and geographical generalizability. Participants who survived dementia-free to age 69–71 and completed neuroimaging may introduce healthy survivor bias. Neuroimaging and cognitive outcomes were measured cross-sectionally at ages 69–71 rather than tracked longitudinally.
Cited by
- supports Cumulative exposure to elevated blood pressure from a young age significantly increases the risk of dementia later in life by causing damage to the small vessels of the brain.