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Fluid biomarkers of Alzheimer’s disease in the Systolic Blood Pressure Intervention Trial
Author(s) -
Pajewski Nicholas M,
Elahi Fanny M,
Ix Joachim H,
Nasrallah Ilya M,
Reboussin David M,
Tamura Manjula Kurella,
Wright Clinton B,
Hinman Jason,
Miller Lindsay M,
Sudduth Tiffany L,
Wilcock Donna M,
Williamson Jeff D
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047258
Subject(s) - medicine , blood pressure , biomarker , cardiology , magnetic resonance imaging , sprint , physical therapy , radiology , chemistry , biochemistry
Background The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive treatment (systolic blood pressure (SBP) target <120 mm Hg) reduces the risk for mild cognitive impairment and slows the progression of white matter lesions detected via magnetic resonance imaging (MRI) as compared to standard treatment (SBP<140 mm Hg). However, it is unclear what pathway(s) mediate this effect. Method We measured plasma beta‐amyloid 40 (Aβ 40 ), beta‐amyloid 42 (Aβ 42 ), total tau, and neurofilament light (NfL) at baseline and during follow‐up (median follow‐up = 3.8 years) in a subgroup of participants 60 years or older that also participated in SPRINT’s MRI imaging substudy (N=542). We modeled changes in each AD biomarker using robust linear mixed models. Result The average baseline age of this subgroup of SPRINT participants was 69.8 ± 7.1 (standard deviation) years; with a mean SBP of 138.2 ± 17.0 mm Hg; and 42.1% were female. At baseline, the strongest plasma biomarker correlations were with age (Spearman’s rho = 0.27 for Aβ 40 and 0.43 for NfL, both P<0.001) and estimated Glomerular Filtration Rate (eGFR; rho ranged from –0.21 for Aβ 42 to ‐0.42 for NfL, all P<0.001). We observed larger increases in each AD biomarker for participants that experienced ≥30% decline in eGFR during follow‐up, which occurs more frequently with intensive treatment. There were no significant between‐group differences for Aβ 40, Aβ 42, or total tau, however intensive treatment was associated with larger increases in NfL during follow‐up (mean change per year (MCPY) = 2.6 pg/ml, 95% CI: 1.8‐3.3), as compared to standard treatment (MCPY = 1.6 pg/ml; 95% CI: 1.3‐1.8). This difference was explained by changes in eGFR (between‐group difference in MCPY adjusting for eGFR = 0.04 pg/ml; 95% CI: ‐0.76 ‐ 0.84). Conclusion In this pilot study of SPRINT participants, after accounting for kidney function, intensive treatment was not associated with significant changes in fluid biomarkers of AD. Our results highlight the need for future studies of blood‐based AD biomarkers to account for renal function, especially within the context of hypertension and vascular disease.