DOI: 10.7272/q6057cv6
title: Associations between vascular risk factors, carotid atherosclerosis and cortical volume and thickness in older adults

description: Data from healthy and cognitively impaired elderly, enriched for
 cerebrovascular disease. Background and Purpose: To investigate whether
 the Framingham Cardiovascular Risk Profile (FCRP) and carotid artery
 intima-media thickness (CIMT) are associated with cortical volume and
 thickness. Results: 152 subjects (82 men) were aged 78 (±7) years old, 94
 had a CDR of 0, 58 had a clinical dementia rating (CDR) of 0.5 and the
 mean mini-mental status examination (MMSE) was 28 ±2. FCRP score was
 inversely associated with total gray matter (GM) volume, parietal and
 temporal GM volume (adjusted p&lt;0.04). FCRP was inversely associated
 with parietal and total cerebral GM thickness (adjusted p&lt;0.03).
 CIMT was inversely associated with thickness of parietal GM only (adjusted
 p=0.04). Including history of myocardial infarction or stroke and
 radiologic evidence of brain infarction, or apoE genotype did not alter
 relationships with FCRP or CIMT. Conclusions: Increased cardiovascular
 risk was associated with reduced GM volume and thickness in regions also
 affected by Alzheimer's disease (AD), independent of infarcts and
 apoE genotype. These results suggest a "double hit" toward
 developing dementia when someone with incipient AD also has high
 cardiovascular risk. Subjects: Consecutive subjects were identified from
 an ongoing, longitudinal, multi-institutional Aging Brain program project
 that recruits subjects with normal cognition to mild cognitive impairment,
 representing a spectrum of low to high vascular risk14. Most participants
 were acquired through community-based recruitment using a protocol
 designed to obtain a demographically diverse cohort, or through sources
 such as stroke clinics and support groups attended by people with high
 vascular risk factors. All participants gave written informed consent in
 accordance with the policies of each institutional review board. Inclusion
 criteria include age 60 or older, with cognitive function in the normal to
 mild cognitive impairment range (Clinical Dementia Rating [CDR] score of 0
 or 0.5) 15. Persons with history of multiple vascular risk factors,
 coronary or carotid disease, myocardial infarction, or ischemic stroke
 were targeted for inclusion, although patients with very large strokes
 that interfered with estimation of cortical volume and thickness were
 excluded. Exclusion criteria included evidence of alcohol or substance
 abuse, head trauma with loss of consciousness lasting longer than 15
 minutes, factors contraindicating MRI, and severe medical illness,
 neurologic or psychiatric disorders unrelated to AD or vascular dementia
 that could significantly affect brain structure (e.g., schizophrenia and
 other psychotic disorders, bipolar disorder, current major depression,
 post-traumatic stress disorder, obsessive-compulsive disorder, liver
 disease, multiple sclerosis, amyotrophic lateral sclerosis). Participant
 demographics by CDR are shown in Table 1. Measures of cardiovascular risk
 and carotid atherosclerosis: The FCRP uses empirically-derived ageand
 gender-adjusted weighting of categorical variables to predict the 10-year
 risk of coronary heart disease and is a weighted sum of: age, gender,
 active smoking, diabetes, systolic blood pressure (and/or use of
 hypertensive medications) and total cholesterol and high-density
 lipoprotein cholesterol levels13. Higher scores indicate greater coronary
 risk. CIMT was used as a measure of subclinical atherosclerosis. CIMT is a
 measures of the thickness of the inner two layers of the carotid artery;
 higher CIMT indicates greater atherosclerosis burden. High-resolution
 B-mode ultrasound images of the right and left common carotid arteries
 were obtained with a 7.5-MHz linear array transducer attached to an ATL
 Apogee ultrasound system (Bothell, WA). CIMT was determined as the average
 of 70 to 100 measurements between the intima-lumen and media-adventitia
 interfaces along a 1 cm length just proximal to the carotid artery bulb at
 the same point of the cardiac cycle using comperterized automated edge
 detection. Right and left CIMT were measured in each individual whenever
 possible. For individuals with CIMT measurements from both sides, the
 maximum of these two quantities was used in subsequent statistical
 analyses. Measure of AD risk: Blood was drawn with the subject's
 consent for apolipoprotein E genotyping. Genotyping was completed for 102
 participants. Subjects with 3/4 or 4/4 combined alleles were classified as
 apoE e4 positive, and those with 3/3 alleles as apoE e4 negative. Because
 the 2/4 combined allele is associated with a lower risk of AD16, these
 subjects were not included in the APOE e4 positive group.
description: Consecutive subjects participating in a prospective cohort study
 of aging and mild cognitive impairment enriched for vascular risk factors
 for atherosclerosis underwent structural MRI scans at 3T and 4T MRI at
 three sites. Freesurfer (v5.1) was used to obtain regional measures of
 neocortical volumes (mm3) and thickness (mm). Multiple linear regression
 was used to determine the association of FCRP and CIMT with cortical
 volume and thickness. MRI: acquisition: Structural T1-weighted MRI scans
 for participants were collected on 3T and 4T MRI systems. Forty-three
 participants were scanned at the University of Southern California using a
 3T General Electric Signal HDx system with an 8-channel head coil.
 Acquired images included a T1-weighted volumetric SPGR (TR = 7 ms, TE =
 2.9 ms, TI= 650 ms, 1 mm3 isotropic resolution). Fifty-four participants
 were scanned at the University of California, Davis research center. Nine
 participants were scanned using a 3T Siemens Magnetom Trio Syngo System
 with an 8-channel head coil. Forty-five were scanned using a 3T Siemens
 Magnetom TrioTim system with an 8-channel head coil. Acquired images for
 all 54 participants included a T1-weighted volumetric MP-RAGE (TR = 2500,
 TE = 2.98, TI = 1100, 1 mm3 isotropic resolution). Thirty-three
 participants were scanned at the San Francisco Veterans Administration
 Medical Center using a 4T Siemens MedSpec Syngo System with an 8-channel
 head coil. A T1-weighted volumetric MP-RAGE scan (TR = 2300, TE = 2.84, TI
 = 950, 1 mm3 isotropic resolution) was acquired. Twenty-two participants
 were scanned at the University of California, San Francisco Neuroscience
 Imaging Center using a 3T Siemens Magnetom TrioTim system with a
 12-channel head coil. Acquired images included a T1-weighted volumetric
 MP-RAGE (TR = 2500, TE = 2.98, TI = 1100, 1 mm3 isotropic resolution).
 MRI: processing: The publicly available Freesurfer v5.1 (http://surfer.nmr.mgh.harvard.edu/) volumetric segmentation and cortical surface reconstruction methods were used to obtain regional measures of neocortical volumes (mm3) and thickness (mm). The reconstructed cortical surface models for each participant were manually inspected to ensure segmentation accuracy; regions with poor segmentation accuracy due to poor image quality or misregistration were excluded from further statistical analyses. Cortical surfaces were automatically parcellated17 and combined to create average cortical thickness and volume for total GM and for frontal, temporal, parietal, and occipital lobar regions. Region of interest volumes and thicknesses by cognitive status are shown in Table 2.