Relations of arterial stiffness and endothelial function to brain aging in the community.
OBJECTIVE
To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging.


METHODS
Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively).


RESULTS
Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05).


CONCLUSIONS
Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.
From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston; Departments of Neurology (S.S., A.S.B., A.J.W., R.A., J.J.H., P.A.W.), Medicine (N.M.H., J.A.V., D.L., E.J.B., R.S.V.), and Biostatistics (A.S.B., J.J.H., M.G.L.), School of Public Health, School of Medicine and the Department of Mathematics (M.G.L.), Boston University, MA; Department of Neurology (C.D.), Center for Neuroscience and Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis; National Heart Lung and Blood Institute (D.L.), NHLBI's Framingham Heart Study (C.W.T., S.S., A.S.B., R.A., D.L., M.G.L., E.J.B., P.A.W., R.S.V.), Framingham; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA.
Connie W
CW
Tsao
Sudha
S
Seshadri
Alexa S
AS
Beiser
Andrew J
AJ
Westwood
Charles
C
Decarli
Rhoda
R
Au
Jayandra J
JJ
Himali
Naomi M
NM
Hamburg
Joseph A
JA
Vita
Daniel
D
Levy
Martin G
MG
Larson
Emelia J
EJ
Benjamin
Philip A
PA
Wolf
Ramachandran S
RS
Vasan
Gary F
GF
Mitchell
D000368:Aged; D000375:Aging / Q000473:pathology*; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology*; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D004727:Endothelium / Q000473:pathology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008365:Manometry / Q000379:methods; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009483:Neuropsychological Tests; D012111:Residence Characteristics; D012189:Retrospective Studies; D018617:Ultrasonography, Doppler, Pulsed; D059289:Vascular Stiffness