Associations between vascular risk factors, carotid atherosclerosis and cortical volume and thickness in older adults

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<0.04). FCRP was inversely associated
with parietal and total cerebral GM thickness (adjusted p<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.