Final outcomes include associations between early and late life cognition and integrity of key white matter tracts, volume of gray and white matter, myelination, brain water content, and visible abnormalities such as white matter lesions and mineral deposits; and influences of vascular risk factors, diet, environment, social metrics, education and genetics on healthy brain aging. It is intended that this information will help to inform and develop strategies for successful cognitive aging.

W hite matter hyperintensities (WMH) are indicators of cerebral small vessel disease 1 and are implicated in the pathogenesis of cognitive impairment, stroke, and dementia. 2 WMH are associated with hypertension and increased risk of stroke, [3][4][5] but the mechanism through which elevated blood pressure (BP) affects the brain is unclear. Advancing age is associated with loss of elasticity in the large arteries and muscular arterioles and increased arterial stiffness. Several risk factors, particularly hypertension, contribute to the stiffness. 3,[6][7][8] Arterial stiffening impairs the damping of the arterial waveform in large arteries and could lead to excessive transmission of BP pulsation to the brain. 9,10 Increasing stiffness of the large central arteries is associated with WMH. [8][9][10][11][12] One explanation for the association between arterial stiffness and WMH is that arterial stiffening exposes small vessels in the brain to high pulsatility, damaging the small vessel wall. [7][8][9] Because this cyclic variation in BP is transmitted to the brain through the internal carotid arteries (ICA), an association among BP, ICA flow parameters, and WMH might be expected. 5 Few studies have compared BP, ICA or middle cerebral artery (MCA) blood flow velocity, and WMH. 9,13 Previous studies 9,10 that investigated BP and ICA or MCA velocity parameters and WMH have focused on the pulse pressure component of BP and the pulsatility index component of the Doppler MCA or ICA waveform. However, pulse pressure is determined by diastolic BP (DBP) and systolic BP (SBP), and the relative contribution of these is a function of age: in young adults, both DBP and SBP increase, whereas in the elderly SBP increases whereas DBP reduces with age.14 Here, we investigated the association between BP measured longitudinally, ICA blood flow velocity parameters, and Abstract-White matter hyperintensities (WMH) are associated with hypertension. We examined interactions among blood pressure (BP), internal carotid artery (ICA) flow velocity parameters, and WMH. We obtained BP measurements from 694 community-dwelling subjects at mean ages 69.6 (±0.8) years and again at 72.6 (±0.7) years, plus brain MRI and ICA ultrasound at age 73±1 years. Diastolic and mean BP decreased and pulse pressure increased, but systolic BP did not change between 70 and 73 years. Multiple linear regression, corrected for vascular disease and risk factors, showed that WMH at the age of 73 years were associated with history of hypertension (β=0.13; P<0.001) and with BP at the age of 70 years (systolic β=0.08, mean β=0.09, diastolic β=0.08; all P<0.05); similar but attenuated associations were seen for BP at the age of 73 years. Lower diastolic BP and higher pulse pressure were associated with higher ICA pulsatility index at the age 73 years (diastolic BP age 70 years: standardized β=−0. 15 Three years later (wave 2), repeat medical and cognitive assessments were conducted (n=866); in addition, at wave 2 they underwent carotid Doppler ultrasound imaging and bra...

Atheromatous middle cerebral artery (MCA) stenosis could cause lacunar stroke by occluding lenticulostriate artery origins, but atheroma is common, and previous studies lacked suitable controls. We aimed to determine if intracranial atheroma was more common in lacunar than in cortical ischaemic stroke. We recruited patients with lacunar stroke and controls with mild cortical stroke, confirmed the stroke subtype with magnetic resonance imaging and used transcranial Doppler ultrasound imaging to record flow velocity and focal stenoses in the basal intracranial arteries 1 month after stroke. We compared ipsi- and contralateral MCA mean flow velocities between stroke subtypes and tested for associations using linear mixed models. Amongst 67 lacunar and 67 mild cortical strokes, mean age 64 and 67 years, respectively, we found no difference in MCA mean flow velocity between cortical and lacunar patients. Increasing age and white matter lesion scores were independently associated with lower MCA flow velocities (0.2 cms^–1 fall in velocity per year increase in age, p = 0.045; 3.75 cms^–1 fall in flow velocity per point increase in white matter lesion score, p = 0.004). We found no intracranial arterial stenoses. MCA atheromatous stenosis is unlikely to be a common cause of lacunar stroke in white populations. Falling velocities with increasing white matter lesion scores may reflect progressive brain tissue loss leaving less tissue to supply.

Background and Purpose-Carotid intima-media thickness (CIMT) is a noninvasive measure of atherosclerosis, but it is unclear whether it is a stronger risk factor for large vessel disease or small vessel disease. Methods-One hundred seven volunteers, aged 75 to 81 years, underwent measurements of CIMT and vascular risk factors and brain MRI (structural and diffusion tensor); those with history of stroke were excluded. Results-In 96 subjects without stroke, there were significant associations between CIMT and markers of large vessel disease (carotid stenosis: ϭ0.28; Pϭ0.01) and intermediary risk factors (systolic blood pressure: ϭ0.34; Pϭ0.001).However, there were no significant associations between CIMT and markers of small vessel disease (white matter lesion load and water diffusion parameters). Conclusions-CIMT