Framingham Cardiovascular Risk Profile Research Articles

Cardiovascular risk moderates aerobic exercise efficacy on executive function in subcortical ischemic vascular cognitive impairment

AbstractBackgroundAerobic exercise can promote cognitive function in adults with Subcortical Ischemic Vascular Cognitive Impairment (SIVCI) by modifying cardiovascular risk factors. However, one’s cardiovascular health may attenuate the benefits of aerobic exercise on cognitive outcomes in SIVCI. We examined whether baseline Framingham Cardiovascular Risk Profile Score (FCRP) moderates the effect of a 6‐month progressive aerobic exercise program on executive function in adults with SIVCI.MethodA secondary analysis of a proof‐of‐concept randomized controlled trial in 71 adults, who were randomized to either: 1) 3x/week progressive aerobic exercise program (AT); or 2) education program (CON). Three executive processes were measured: 1) response inhibition by Stroop Colour Word Test; 2) working memory by digits backward test, and 3) set shifting by the Trail Making Test (B‐A). Baseline cardiovascular risk was calculated using the FCRP, and participants were classified as either low risk (<20% FCRP score; LCVR) or high risk (>20% FCRP score; HCVR). A complete case analysis (n=57) was conducted using an analysis of covariance (ANCOVA) to evaluate between‐group differences in the three executive processes. Age, baseline Montreal Cognitive Assessment score, education, and baseline score for the outcome variable were entered as covariates in all models.ResultA significant interaction was found between FCRP and group (AT or CON) for the digit span backward (F(1,49)=4.67, p=0.03) and the Trail Making Test (F(1,50)=4.09, p=0.04). On the digit span backward test, AT improved performance compared to CON (3.74±.33 vs. 2.75±.46) in those with LCVR, while in those with HCVR, AT did not improve performance compared to CON (2.97±.45 vs. 3.76±.41). Similarly, for the Trail Making Test (B‐A), AT improved performance compared to CON (52.66±13.27 vs. 80.12±17.82) in those with LCVR, while AT was not beneficial compared to CON in those with HCVR (98.80±18.06 vs. 59.92±17.09).ConclusionBaseline cardiovascular risk significantly moderates the efficacy of aerobic exercise on working memory and set shifting in adults with SIVCI. Our findings highlight the importance of intervening early in the disease course of SIVCI, when cardiovascular risk may be lower, to reap maximum benefits of aerobic exercise.

Global Cardiovascular Risk Profile and Cerebrovascular Abnormalities in Presymptomatic Individuals with CADASIL or Autosomal Dominant Alzheimer's Disease.

Cardiovascular risk factors increase the risk of developing dementia, including Alzheimer's disease and vascular dementia. Studying individuals with autosomal dominant mutations leading to the early onset of dementia, this study examines the effect of the global cardiovascular risk profile on early cognitive and neuroimaging features of Alzheimer's disease and vascular dementia. We studied 85 non-demented and stroke-free individuals, including 20 subjects with Presenilin1 (PSEN1) E280A mutation leading to the early onset of autosomal dominant Alzheimer's disease (ADAD), 20 subjects with NOTCH3 mutations leading to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to the early onset of vascular dementia, and 45 non-affected family members (non-carriers). All subjects underwent clinical and neuropsychological evaluations and an MRI. The global cardiovascular risk profile was estimated using the office-based Framingham Cardiovascular Risk Profile (FCRP) score. In individuals with CADASIL, a higher FCRP score was associated with a reduced hippocampal volume (B = -0.06, p < 0.05) and an increased severity of cerebral microbleeds (B = 0.13, p < 0.001), lacunes (B = 0.30, p < 0.001), and perivascular space enlargement in the basal ganglia (B = 0.50, p < 0.05). There was no significant association between the FCRP score and neuroimaging measures in ADAD or non-carrier subjects. While the FCRP score was related to performance in executive function in non-carrier subjects (B = 0.06, p < 0.05), it was not significantly associated with cognitive performance in individuals with CADASIL or ADAD. Our results suggest that individuals with CADASIL and other forms of vascular cognitive impairment might particularly benefit from early interventions aimed at controlling cardiovascular risks.

The impact of hippocampal segmentation methods on correlations with clinical data.

In vivo measurement of hippocampal volume with magnetic resonance imaging (MRI) has become an important element in neuroimaging research. However, hippocampal volumetric findings and their relationship with cardiovascular risk factors and memory performance are still controversial and inconsistent for non-demented adults. To compare total and regional hippocampal volumes from manual tracing and automated Freesurfer segmentation methods and their relationship with mid-life clinical data and late-life verbal episodic memory performance in older women. This study used structural MRI datasets from 161 women who were scanned in 2012 and underwent neuropsychological assessments. Of these participants, 135 women had completed baseline measures of cardiovascular risk factors in 1992. Our results showed a significant correlation between manual tracing and automated Freesurfer output segmentations of total (r = 0.71), anterior (r = 0.65), and posterior (r = 0.38) hippocampal volumes. Mid-life Framingham Cardiovascular Risk Profile score is not associated with late-life hippocampal volumes, adjusted for intracranial volume, age, education, and apolipoprotein E gene ε4 status. Anterior hippocampal volume segmented either with manual tracing or automated Freesurfer software is sensitive to changes in mid-life high-density lipoprotein (HDL) cholesterol level, while posterior hippocampal volume is linked with verbal episodic memory performance in elderly women. These findings support the use of Freesurfer automated segmentation measures for large datasets as being highly correlated with the manual tracing method. In addition, our results suggest intervention strategies that target mid-life HDL cholesterol level in women.

CARDIOVASCULAR RISK MODERATES THE EFFECT OF RESISTANCE TRAINING ON PHYSICAL PERFORMANCE IN OLDER ADULT WOMEN

We aimed to examine whether the Framingham Cardiovascular Risk Profile Score (FCRP) moderates the effect of progressive resistance training (RT) on mobility in older adult women. This is an exploratory analysis of a single-blind, 12-month randomized controlled trial in 155 omen, aged 65 to 75 years old, who were randomized to: 1x/week progressive RT; or 2x/week progressive RT program; or 2x/week balance and tone (BAT). At baseline and trial completion, mobility was measured using the Short Physical Performance Battery (SPPB). The SPPB is a composite measure of usual gait speed, standing balance, and sit to stand performance; scores < 9/12 are indicative of functional decline. Baseline 10-year cardiovascular risk was calculated using the FCRP. Participants were classified as either low risk (<16.5% FCRP score; LCVR) or high risk ≥16.5% FCRP score; HCVR). A complete case analysis (n=126) was conducted using a two-way analysis of covariance (ANCOVA) to evaluate the interaction effect of group by FCRP risk on SPPB scores at trial completion; baseline SPPB scores and age in years were entered as covariates. There was a significant interaction effect (F(1,126)=3.74, p=0.027). At trial completion, both 1x/RT and 2x/RT participants with HCVR demonstrated greater SPPB scores than those with LCVR (11.59 vs. 11.38 for 1x/week; 11.86 vs 11.46 for 2x/week). In contrast, BAT participants with HCVR demonstrated worse SPPB scores than those with LCVR (11.18 vs 11.66). Our data suggest that RT may be more efficacious for improving mobility in older women with higher cardiovascular risk than women with lower risk.

The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women

Cerebral White Matter Hyperintensity (WMH) lesions have been identified as markers of cerebrovascular diseases and they are associated with increased risk of cognitive impairment. In this study, we investigated the relationship between midlife cardiovascular risk factors and late life WMH volumes two decades later, and examined their association with cognitive performance. 135 participants from the Women's Healthy Ageing Project had completed midlife cardiovascular risk measurement in 1992 and late life brain MRI scan and cognitive assessment in 2012. In these community-dwelling normal aging women, we found that higher midlife Framingham Cardiovascular Risk Profile (FCRP) score was associated with greater WMH volume two decades later, and was predominantly driven by the impact of HDL cholesterol level, controlling for age, education and APOE ε4 status. Structural equation modelling demonstrated that the relationship between midlife FCRP score and late life executive function was mediated by WMH volume. These findings suggest intervention strategies that target major cardiovascular risk factors at midlife might be effective in reducing the development of WMH lesions and thus late life cognitive decline.

Interactions between Atrial Fibrillation, Cardiovascular Risk Factors, and ApoE Genotype in Promoting Cognitive Decline in Patients with Alzheimer's Disease: A Prospective Cohort Study.

An association between non-valvular atrial fibrillation (NVAF) and cognitive impairment has been hypothesized. We sought to evaluate whether and how permanent NVAF (pNVAF) is associated with progression of cognitive impairment in patients with Alzheimer's disease (AD) in the presence of vascular or genetic risk factors. 310 consecutive patients affected by mild-moderate AD were included and followed for a 24-month period. At the end of the follow-up, based on the results of the neuropsychological evaluation patients were classified as stable or deteriorated to severe AD. Clinical history, therapy, time in therapeutic range for anticoagulation, Framingham cardiovascular risk profile (FCRP), CHA2DS2-VASc score, Mini-Mental State Examination (MMSE), ApoE genotype, brain CT-scan, carotid ultrasound, and ECG were collected. Binary logistic and path analysis were adopted to assess relationships between pNVAF, ApoE, and cognitive outcome. Despite anticoagulant therapy, pNVAF was associated with lower entry MMSE, higher mean intima-media thickness (mIMT) and higher FCRP. Among patients carrying ApoE ɛ4 allele and affected by pNVAF, the lowest MMSE (14.90±7.62) and the highest mIMT (1.16±0.17 mm) and FCRP (26.24±3.96) values were detected. In this group, the risk of cognitive deterioration reached the highest probability. pNVAF was associated with an increased cognitive deterioration in subjects with high FCRP, CHA2DS2-VASc, or mIMT. pNVAF seems to identify AD patients with a significant atherosclerotic burden and reduced cognitive performances. The interaction between pNVAF and ApoE ɛ4 genotype, especially with aggregated risk factors and an advanced stage of vascular damage is associated with higher risk of fast cognitive deterioration.

Framingham Risk Score and the Risk of Progression from Mild Cognitive Impairment to Dementia.

Mild cognitive impairment (MCI) often represents the clinical manifestation of cognitive deterioration preceding Alzheimer's disease (AD). Currently, there are no reliable approaches for an objective evaluation of the risk of developing AD in MCI patients. The aim of this study was to verify whether the Framingham cardiovascular risk profile (FCRP) could be useful to identify patients at the highest risk of conversion from MCI to AD. Patients with amnestic MCI (aMCI) were carefully investigated to assess their vascular risk profile. They were also submitted to a comprehensive neuropsychological evaluation. The FCRP was calculated for each patient and the apolipoprotein E (ApoE) genotype was determined from peripheral blood cells. The main outcome was defined as a conversion to AD within 24 months after inclusion. 385 consecutive aMCI subjects were included. Age, FCRP, and vascular age showed a fairly predictive value on conversion to AD. Selecting the subpopulation of ApoE ɛ4 carriers, we observed that FCRP had an increased performance in predicting the conversion. The rate of conversion increased from 12.5% in the FCRP low-risk group to 43.2% in the high-risk group (p < 0.0001). ApoE ɛ4 carriers had a 3.7-times increased probability of conversion with respect to the other subjects (p < 0.0001). FCRP assessment could be considered a reliable approach to predict conversion to AD in aMCI subjects. The presence of ApoE ɛ4 increases significantly the risk of conversion. These data confirm the narrow relationship between genetic and vascular risk factors in influencing the evolution of cognitive impairment.

Cardiovascular risk profiling of patients of an Urban Health Centre of a tertiary care teaching hospital in South India

Abstract Background Addressing all modifiable risk factors in a composite manner, instead of treating individual risk factors is the current approach in the management of cardiovascular diseases. In patients, attending chronic disease clinic in Urban Health Centre (UHC) functioning under a tertiary care teaching hospital, this study aims to assess 10-year cardiovascular risk using ‘WHO/ISH Cardiovascular Risk Prediction Charts’ and ‘Framingham General Cardiovascular Risk Profile using lipid levels’ and compare the level of agreement between the results obtained. Methodology A retrospective record review was carried out in urban chronic disease clinic during the months of May and June 2013. Records of 280 patients attending the Urban Health Centre were screened using a structured proforma and 180 of them were included subject to selection criteria. The analysis was carried out using IBM SPSS v 21. 10-year cardiovascular risk was calculated using the joint WHO/ISH charts and the General Framingham Cardiovascular Risk Profile charts. Level of agreement between the risk scores was compared using kappa statistics. Institution ethics committee approval was obtained before starting the project. Results 81.7% of the patients were women with a median age of 58 years. Less than half of the patients (45%) had hypertension and another 37.2% had both diabetes and hypertension. 71.6% of the patients had a Conclusion Framingham Risk Profile was found to identify more patients as belonging to the higher risk category as compared to WHO/ISH charts.

Framingham risk score can predict cognitive decline progression in Alzheimer's disease

The role of vascular factors in influencing cognitive decline has been extensively investigated, and some difficulties in defining their weight in dementia pathogenesis have emerged. The aim of the study was to investigate the relevance of the Framingham cardiovascular risk profile (FCRP) in influencing cognitive deterioration in a population of Alzheimer's disease (AD) patients. Two hundred eighty-four consecutive AD patients were enrolled. For each patient, FCRP score was calculated. We did a 1-year follow-up to quantify the cognitive decline by recording changes in the Clinical Dementia Rating score. The FCRP score predicted cognitive deterioration with an area under the curve of 0.63 (95% confidence interval: 0.57–0.69; p < 0.0001). In the subpopulation of patients with a genetic increased predisposition to develop cognitive deterioration and with an advanced vascular impairment, the FCRP predictive value significantly increased with an area under the curve of 0.77 (95% confidence interval: 0.52–0.93; p < 0.05). Our findings show that FCRP can predict the progression of deterioration in AD patients. This was particularly evident in patients with major genetic and atherosclerotic risk factors.

Cognitive dysfunctions in middle-aged type 2 diabetic patients and neuroimaging correlations: a cross-sectional study.

The aim was to assess the neuropsychological performance of a group of middle-aged patients with well-controlled type 2 diabetes mellitus (T2DM) and to examine whether the neuropsychological deficits correlate with structural and functional brain alterations. We compared 25 subjects with T2DM aged 45-65 years with 25 control participants matched for age, gender, and educational level. The neuropsychological battery was designed to examine executive functions, attention, information processing speed, and verbal memory. Severity of depression was assessed using the Hamilton Depression Rating Scale and cardiovascular risk factors were assessed using the Framingham Cardiovascular Risk Profile Score. The presence of at least one APOEε4 allele was determined. Reduced gray matter density was analyzed using voxel-based morphometry and brain glucose metabolic changes were assessed by 18FDG-PET. T2DM subjects had significantly lower scores than subjects without T2DM in the Trail-making Test B (p < 0.004), Color-Word Stroop test (p < 0.005), Semantic Fluency (p < 0.006), Digit-Symbol modalities test (p < 0.02), Text Recall from the Wechsler Memory Scale (p < 0.0001), Rey-Osterrieth Complex Figure-copy (p < 0.004), and delayed reproduction (p < 0.03). Worse executive functions and memory functioning correlated predominantly with less gray matter density and reduced glucose metabolism in the orbital and prefrontal cortex, temporal (middle gyrus, parahippocampus and uncus), and cerebellum regions (p < 0.001). T2DM subjects presented cognitive dysfunctions compared with controls. Clinical-neuroimaging correlations corresponded to brain changes (reduced gray matter density and glucose metabolism) mainly in fronto-temporal areas.

Re: "Clinical Usefulness of the Framingham Cardiovascular Risk Profile beyond Its Statistical Performance: The Tehran Lipid and Glucose Study"

Khalili et al. (1) evaluated the clinical utility of the Framingham cardiovascular risk model in a Middle Eastern cohort study. We commend the authors for their use of highly relevant measures of model performance, the net benefit (2, 3) and net benefit fraction (4, 5). However, we would like to make several points regarding their interpretation and reporting of these measures. Interpretation of the net benefit and net benefit fraction The population net benefit (NB) of a risk model, used to classify individuals as being at high 10-year risk of cardiovascular disease using the risk threshold rH, is (1) where B is the benefit of classifying as high-risk a subject who would develop cardiovascular disease absent treatment (a “cardiovascular event”), H is the harm of classifying as high-risk a subject who would not develop cardiovascular disease absent treatment (a “cardiovascular nonevent”), TPR(rH) and FPR(rH) are the true- and false-positive rates associated with this risk threshold, and ρ is the proportion of subjects who experience cardiovascular events. Vickers and Elkin (2) set B to 1, so that the units are true positive classifications, and use the optimal risk threshold rH = H/H + B (6) in order to rewrite equation 1 as (2) Baker et al. (4, 5) scale equation 2 by ρ, which is the maximum possible net benefit for a model that classifies as high-risk all cardiovascular events and all others as low-risk. The net benefit fraction (NBF) is therefore (3) Khalili et al. interpret NBF(0.2) = 0.156 for the Framingham risk model applied to women as “the fraction of the incidence rate that could be predicted and prevented” (1, p. 178). However, this is not a valid interpretation. Their interpretation seems to relate to the TPR of the model, whereas NBF(0.2) = 0.156 is more accurately interpreted as a discounted TPR; the TPR is offset by the FPR where false-positives are put on the same scale as true-positives (7). We prefer to interpret NBF(0.2) = 0.156 as the same benefit that would be achieved by classifying as high-risk 15.6% of cardiovascular events and none of the nonevents (2, 3). The authors' interpretation also suggests that all cardiovascular events classified as high-risk would necessarily be prevented; however, this would depend on the efficacy of subsequent interventions. Net benefit for different subsets of the population Net benefit curves, which plot the net benefit in equation 2 versus the risk threshold rH (2, 3), are also used by Khalili et al. The authors recommend these curves for examining the net benefit for a range of risk thresholds, given that different patient subgroups may have different side effects of interventions and therefore different risk thresholds. However, the net benefit curve shows the total population net benefit at each risk threshold. Two points on the curve cannot be interpreted as the net benefits for 2 different subpopulations because, if the risk distribution in the subpopulation differs from the risk distribution in the whole population, the net benefit in the subpopulation is different from the net benefit in the whole population at that threshold. For example, men and women in the Middle Eastern cohort have different values for TPR, FPR, and ρ and therefore have net benefits that differ from the population net benefit shown on the net benefit curve. Recommendation We have several practical recommendations. The first is to stratify any analysis by important patient characteristics that affect risk threshold—for example, gender as in the study by Khalili et al. (1). The second is to report the net benefit fraction together with its constituents, the TPR and FPR, over a range of risk thresholds. Seeing these individual components helps in digesting the net benefit. Knowing the TPR and FPR is also helpful when risk thresholds are chosen “irrationally.” That is, the net benefit in equation 2 assumes that the risk threshold reflects the cost-benefit ratio, rH = H/H + B. However, individuals or policy-makers may choose risk thresholds in ways that do not reflect the cost-benefit ratio. For example, in their commentary accompanying Khalili et al.'s article, D'Agostino and Pencina (8) suggest that the risk threshold rH = 0.2 was chosen without regard to cost-benefit considerations. Reporting the TPR and FPR as a function of risk threshold allows the reader to choose a threshold and to perform any calculus desired to take into consideration both components of model performance.

Associations Among Vascular Risk Factors, Carotid Atherosclerosis, and Cortical Volume and Thickness in Older Adults

The purpose of this study was to investigate whether the Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness are associated with cortical volume and thickness. 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 3-T and 4-T MRI at 3 sites. Freesurfer (Version 5.1) was used to obtain regional measures of neocortical volumes (mm3) and thickness (mm). Multiple linear regression was used to determine the association of Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness with cortical volume and thickness. One hundred fifty-two subjects (82 men) were aged 78 (±7) years, 94 had a clinical dementia rating of 0, 58 had a clinical dementia rating of 0.5, and the mean Mini-Mental State Examination was 28±2. Framingham Cardiovascular Risk Profile score was inversely associated with total gray matter volume and parietal and temporal gray matter volume (adjusted P<0.04). Framingham Cardiovascular Risk Profile was inversely associated with parietal and total cerebral gray matter thickness (adjusted P<0.03). Carotid artery intima-media thickness was inversely associated with thickness of parietal gray matter only (adjusted P=0.04). Including history of myocardial infarction or stroke and radiological evidence of brain infarction, or apolipoprotein E genotype did not alter relationships with Framingham Cardiovascular Risk Profile or carotid artery intima-media thickness. Increased cardiovascular risk was associated with reduced gray matter volume and thickness in regions also affected by Alzheimer disease independent of infarcts and apolipoprotein E genotype. These results suggest a "double hit" toward developing dementia when someone with incipient Alzheimer disease also has high cardiovascular risk.

Invited Commentary: Clinical Usefulness of the Framingham Cardiovascular Risk Profile Beyond Its Statistical Performance

Framingham risk functions (FRFs) have been developed for over 50 years. There have been numerous applications of them and within the last few decades they have been used in drug treatment guidelines. The Adult Treatment Panel III explicitly used a coronary heart disease FRF in their guidelines for cholesterol drug treatment. Evaluation of these functions has traditionally involved discrimination and calibration measures. One major goal of the FRFs is to see if they are valid in non-Framingham settings. In this issue of the Journal, Khalili et al. (Am J Epidemiol. 2012;176(3):177-186) apply a recent global cardiovascular disease FRF to the data from their Tehran Lipid and Glucose Study and demonstrate that the cardiovascular disease FRF performs extremely well: as good as the best risk function generated from the Tehrani data. The FRF is transportable to the Tehrani data without need for any calibration adjustment. The investigators then move beyond the traditional discrimination and calibration evaluations, look for utility, and apply the decision theory concepts of net benefit fraction. This application makes assumptions about treatment guidelines. There are both useful and negative aspects of this application, and caution is advised against a too enthusiastic acceptance of it to evaluate prediction rules for primary prevention of cardiovascular disease.

Clinical Usefulness of the Framingham Cardiovascular Risk Profile Beyond Its Statistical Performance: The Tehran Lipid and Glucose Study

The utility of a risk function in clinical practice is an important concept that has received insufficient attention. The authors evaluated the clinical usefulness of the Framingham risk function (FRF) for cardiovascular disease in a Middle Eastern population (2,640 men and 3,584 women aged 30-74 years) free of cardiovascular disease at baseline in 1999. They calculated the net benefit fraction for treatment of subjects with an estimated 10-year risk of ≥10% and also ≥20%, where the net benefit fraction is a weighted sum of true-positive and false-positive rates divided by incidence, as estimated by Kaplan-Meier analysis. The authors drew a decision curve by plotting the net benefit fraction against a wide range of risk thresholds for treatment. The cumulative incidence of cardiovascular disease was 7.6% and 12.3% in women and men, respectively. The FRF had a C index of 0.832 in women and 0.785 in men with a reasonable calibration. On the basis of the net benefit fraction, about 50% of the incidence in men and women could be appropriately treated by using the 10% threshold; however, the FRF was not useful at the 20% threshold, especially in women. In both genders, usefulness of the FRF was as good as the function derived directly from Tehrani data with the same variables; however, it could be useful in low thresholds for treatment.

P1-31 Clinical usefulness of Framingham cardiovascular risk profile during a 10-year follow-up in Iran

IntroductionClinical usefulness of a risk function is a new concept that should be considered beyond the traditional checking of discrimination and calibration for performance of a model. Framingham risk score...

Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia

Vascular risk factors affect cerebral blood flow (CBF) and cerebral vascular reactivity, contributing to cognitive decline. Hippocampus is vulnerable to both Alzheimer's disease (AD) pathology and ischemia; nonetheless, the information about the impact of vascular risk on hippocampal perfusion is minimal. Cognitively, healthy elderly (NL=18, 69.9±6.7 years) and subjects with mild cognitive impairment (MCI=15, 74.9±8.1 years) were evaluated for the Framingham cardiovascular risk profile (FCRP). All underwent structural imaging and resting CBF assessment with arterial spin labeling (ASL) at 3T magnetic resonance imaging (MRI). In 24 subjects (NL=17, MCI=7), CBF was measured after a carbon dioxide rebreathing challenge. Across all subjects, FCRP negatively correlated with hippocampal (ρ=-0.41, P=0.049) and global cortical (ρ=-0.46, P=0.02) vasoreactivity to hypercapnia (VR(h)). The FCRP-VR(h) relationships were most pronounced in the MCI group: hippocampus (ρ=-0.77, P=0.04); global cortex (ρ=-0.83, P=0.02). The FCRP did not correlate with either volume or resting CBF. The hippocampal VR(h) was lower in MCI than in NL subjects (Z=-2.0, P=0.047). This difference persisted after age and FCRP correction (F([3,20])=4.6, P=0.05). An elevated risk for vascular pathology is associated with a reduced response to hypercapnia in both hippocampal and cortical tissue. The VR(h) is more sensitive to vascular burden than either resting CBF or brain volume.

An inverse association of cardiovascular risk and frontal lobe glucose metabolism

To investigate associations between vascular risk profile and cerebral glucose metabolism. Subjects ranged from normal to having dementia (age >55 years) and underwent neuropsychological testing, MRI, and FDG PET scanning (n = 58). The Framingham Cardiovascular Risk Profile (FCRP) and its individual components were used as covariates in regression analyses with each PET scan using SPM2. Analyses revealed broad areas of the frontal lobe in which higher FCRP was associated with lower normalized glucose metabolism including the superior medial frontal, superior frontal and superior orbital frontal cortex and the ventrolateral prefrontal cortex. Significant associations were predominately found in the left hemisphere. Independent component analyses revealed interesting regions but further confirm the relevance of the integrative measure of coronary risk. Although the mechanism of this association bears further investigation, this finding provides further evidence that vascular risk factors have malignant effects on the brain, particularly in the prefrontal cortex.