@article {677, title = {Correlates of aortic stiffness in elderly individuals: a subgroup of the Cardiovascular Health Study.}, journal = {Am J Hypertens}, volume = {15}, year = {2002}, month = {2002 Jan}, pages = {16-23}, abstract = {

BACKGROUND: Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals.

METHODS: Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4\% women, 25.3\% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998.

RESULTS: Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993.

CONCLUSIONS: In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima-media thickness, heart rate, and decreased physical activity measured several years earlier.

}, keywords = {Aged, Aged, 80 and over, Aging, Aorta, Female, Heart Rate, Humans, Hypertension, Insulin Resistance, Longitudinal Studies, Male, Pulsatile Flow, Risk Factors, Sex Distribution}, issn = {0895-7061}, doi = {10.1016/s0895-7061(01)02228-2}, author = {Mackey, Rachel H and Sutton-Tyrrell, Kim and Vaitkevicius, Peter V and Sakkinen, Pamela A and Lyles, Mary F and Spurgeon, Harold A and Lakatta, Edward G and Kuller, Lewis H} } @article {730, title = {Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {107}, year = {2003}, month = {2003 Mar 18}, pages = {1372-7}, abstract = {

BACKGROUND: Few studies have examined associations of fish consumption with ischemic heart disease (IHD) risk among older adults or how different types of fish meals relate to IHD risk.

METHODS AND RESULTS: In a population-based prospective cohort study, usual fish consumption was ascertained at baseline among 3910 adults aged > or =65 years and free of known cardiovascular disease in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. Over 9.3 years{\textquoteright} mean follow-up, there were 247 IHD deaths (including 148 arrhythmic deaths) and 363 incident nonfatal myocardial infarctions (MIs). After adjustment for potential confounders, consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death (P for trend=0.001) and arrhythmic IHD death (P=0.001) but not nonfatal MI (P=0.44), with 49\% lower risk of total IHD death and 58\% lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of total IHD death, arrhythmic IHD death, or nonfatal MI but rather with trends toward higher risk.

CONCLUSIONS: Among adults aged > or =65 years, modest consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower risk of IHD death, especially arrhythmic IHD death. Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed.

}, keywords = {Aged, Animals, Arrhythmias, Cardiac, Diet, Eating, Fatty Acids, Omega-3, Female, Fishes, Humans, Male, Myocardial Infarction, Myocardial Ischemia, Prospective Studies, Risk, Tuna}, issn = {1524-4539}, doi = {10.1161/01.cir.0000055315.79177.16}, author = {Mozaffarian, Dariush and Lemaitre, Rozenn N and Kuller, Lewis H and Burke, Gregory L and Tracy, Russell P and Siscovick, David S} } @article {741, title = {C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {108}, year = {2003}, month = {2003 Jul 15}, pages = {166-70}, abstract = {

BACKGROUND: Increased carotid artery intima-media thickness (IMT) and elevated C-reactive protein (CRP) are both associated with the occurrence of stroke. We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT.

METHODS AND RESULTS: We studied 5417 participants aged 65 years or older without preexisting stroke or chronic atrial fibrillation who were participants in the Cardiovascular Health Study. The hazard ratio of incident ischemic stroke was estimated by Cox proportional hazards regression. During 10.2 years of follow-up, 469 incident ischemic strokes occurred. The adjusted hazard ratios for ischemic stroke in the 2nd to 4th quartiles of baseline CRP, relative to the 1st quartile, were 1.19 (95\% CI 0.92 to 1.53), 1.05 (95\% CI 0.81 to 1.37), and 1.60 (95\% CI 1.23 to 2.08), respectively. With additional adjustment for carotid IMT, there was little confounding. The association of CRP with stroke was significantly different depending on IMT (P<0.02), with no association of CRP with stroke among those in the lowest IMT tertile and a significant association among those with higher levels of IMT.

CONCLUSIONS: We conclude that elevated CRP is a risk factor for ischemic stroke, independent of atherosclerosis severity as measured by carotid IMT. The association of CRP with stroke is more apparent in the presence of a higher carotid IMT. CRP and carotid IMT may each be independent integrals in determining the risk of ischemic stroke.

}, keywords = {Aged, Brain Ischemia, C-Reactive Protein, California, Carotid Arteries, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Maryland, North Carolina, Odds Ratio, Pennsylvania, Proportional Hazards Models, Risk Assessment, Risk Factors, Stroke, Tunica Intima, Tunica Media, Ultrasonography}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000079160.07364.6A}, author = {Cao, Jie J and Thach, Chau and Manolio, Teri A and Psaty, Bruce M and Kuller, Lewis H and Chaves, Paulo H M and Polak, Joseph F and Sutton-Tyrrell, Kim and Herrington, David M and Price, Thomas R and Cushman, Mary} } @article {842, title = {Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.}, journal = {Atherosclerosis}, volume = {181}, year = {2005}, month = {2005 Jul}, pages = {175-83}, abstract = {

Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.

}, keywords = {Aged, Aging, Carboxypeptidase B2, Cause of Death, Cohort Studies, Female, Genotype, Health Status, Humans, Inflammation, Longevity, Male, Middle Aged, Plasminogen Activator Inhibitor 1, Polymorphism, Genetic, Promoter Regions, Genetic, Prospective Studies, Risk Factors, Thrombosis}, issn = {0021-9150}, doi = {10.1016/j.atherosclerosis.2005.01.028}, author = {Reiner, Alexander P and Diehr, Paula and Browner, Warren S and Humphries, Stephen E and Jenny, Nancy S and Cushman, Mary and Tracy, Russell P and Walston, Jeremy and Lumley, Thomas and Newman, Anne B and Kuller, Lewis H and Psaty, Bruce M} } @article {829, title = {Coronary artery calcium: associations with brain magnetic resonance imaging abnormalities and cognitive status.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {609-15}, abstract = {

OBJECTIVES: To evaluate the association between coronary atherosclerosis and subclinical brain magnetic resonance imaging (MRI) abnormalities and between coronary atherosclerosis and abnormal cognitive function (dementia/mild cognitive impairment).

DESIGN: Cross-sectional.

SETTING: The Cardiovascular Health Study (CHS), an epidemiological study of risk factors for cardiovascular disease in older adults.

PARTICIPANTS: Four hundred nine men and women, mean age 79, recruited from the Pittsburgh center of the CHS.

MEASUREMENTS: Coronary atherosclerosis was defined according to the level of coronary artery calcification (CAC), as measured using electronic beam tomography. Subclinical brain MRI abnormalities included ventricular enlargement, white matter hyperintensities, and number of subcortical brain infarcts. Brain MRI and CAC measurements were performed between 1998 and 2000 at the Pittsburgh center of the CHS. Prevalence of brain MRI abnormalities and abnormal cognitive status were examined across quartiles of the CAC score, before and after controlling for age. Multivariate logistic regression models were used to assess whether CAC level was associated with abnormalities of brain MRI or abnormal cognitive status.

RESULTS: Older adults with high CAC scores were more likely to have more-severe brain MRI abnormalities, including subcortical infarction and high white matter hyperintensities. The associations between CAC and ventricular enlargement showed a similar but not significant trend. The presence of any of the MRI abnormalities attenuated the association between CAC and abnormal cognitive status.

CONCLUSION: Older adults with higher levels of CAC were more likely to have more-severe brain MRI abnormalities and abnormal cognitive status.

}, keywords = {Aged, Brain, Calcinosis, Cognition Disorders, Coronary Artery Disease, Cross-Sectional Studies, Dementia, Female, Humans, Logistic Models, Magnetic Resonance Imaging, Male, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53208.x}, author = {Rosano, Caterina and Naydeck, Barbara and Kuller, Lewis H and Longstreth, William T and Newman, Anne B} } @article {845, title = {C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study.}, journal = {Circulation}, volume = {112}, year = {2005}, month = {2005 Jul 05}, pages = {25-31}, abstract = {

BACKGROUND: High C-reactive protein (CRP) is associated with increased coronary heart disease risk. Few long-term data in the elderly are available.

METHODS AND RESULTS: Baseline CRP was measured in 3971 men and women > or =65 years of age without prior vascular diseases; 26\% had elevated concentrations (>3 mg/L). With 10 years of follow-up, 547 participants developed coronary heart disease (CHD; defined as myocardial infarction or coronary death). With elevated CRP, the 10-year cumulative CHD incidences were 33\% in men and 17\% in women. The age-, ethnicity-, and sex-adjusted relative risk of CHD for CRP >3 mg/L compared with <1 mg/L was 1.82 (95\% CI, 1.46 to 2.28). Adjusting for conventional risk factors reduced the relative risk to 1.45 (95\% CI, 1.14 to 1.86). The population-attributable risk of CHD for elevated CRP was 11\%. Risk relationships did not differ in subgroups defined by baseline risk factors. We assessed whether CRP improved prediction by the Framingham Risk Score. Among men with a 10-year Framingham-predicted risk of 10\% to 20\%, the observed CHD incidence was 32\% for elevated CRP. Among women, CRP discriminated best among those with a 10-year predicted risk >20\%; the incidences were 31\% and 10\% for elevated and normal CRP levels, respectively.

CONCLUSIONS: In older men and women, elevated CRP was associated with increased 10-year risk of CHD, regardless of the presence or absence of cardiac risk factors. A single CRP measurement provided information beyond conventional risk assessment, especially in intermediate-Framingham-risk men and high-Framingham-risk women.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, C-Reactive Protein, Coronary Disease, Female, Humans, Incidence, Inflammation, Male, Myocardial Infarction, Predictive Value of Tests, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.104.504159}, author = {Cushman, Mary and Arnold, Alice M and Psaty, Bruce M and Manolio, Teri A and Kuller, Lewis H and Burke, Gregory L and Polak, Joseph F and Tracy, Russell P} } @article {945, title = {Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia.}, journal = {Alzheimer Dis Assoc Disord}, volume = {21}, year = {2007}, month = {2007 Jan-Mar}, pages = {14-24}, abstract = {

Expansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes.

}, keywords = {Aged, Aged, 80 and over, Case-Control Studies, Cerebral Ventricles, Cognition Disorders, Dementia, Disease Progression, Female, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Severity of Illness Index, Time Factors}, issn = {0893-0341}, doi = {10.1097/WAD.0b013e318032d2b1}, author = {Carmichael, Owen T and Kuller, Lewis H and Lopez, Oscar L and Thompson, Paul M and Dutton, Rebecca A and Lu, Allen and Lee, Sharon E and Lee, Jessica Y and Aizenstein, Howard J and Meltzer, Carolyn C and Liu, Yanxi and Toga, Arthur W and Becker, James T} } @article {1006, title = {Coronary artery calcium, carotid artery wall thickness, and cardiovascular disease outcomes in adults 70 to 99 years old.}, journal = {Am J Cardiol}, volume = {101}, year = {2008}, month = {2008 Jan 15}, pages = {186-92}, abstract = {

Few population studies have evaluated the associations of both coronary artery calcium (CAC) and carotid ultrasound with cardiovascular events, especially in adults >70 years of age. At the Pittsburgh Field Center of the Cardiovascular Health Study, 559 men and women, mean age 80.2 (SD 4.1) years had CAC score assessed by electron beam computerized tomographic scan and common and internal carotid artery intimal medial wall thickness (CCA-IMT and ICA-IMT) by carotid ultrasound between 1998 and 2000 and were followed for total and incident cardiovascular disease events through June 2003. Crude rates and hazard ratios for total and incident events were examined with and without adjustment for cardiovascular risk factors. After 5 years, there were 127 cardiovascular disease events, 48 myocardial infarctions or cardiovascular disease deaths, and 28 strokes or stroke deaths. Total and incident cardiovascular disease event rates were higher in each quartile of CAC and CCA-IMT, but not of ICA-IMT. For total cardiovascular disease, the adjusted hazard ratio for the fourth versus first quartile of CAC was 2.1 (95\% confidence interval 1.2 to 3.9) and for CCA-IMT was 2.3 (95\% confidence interval 1.3 to 4.1). The CCA-IMT was more strongly related to stroke risk than was CAC, although CAC was also an important predictor of stroke. No significant gender differences were found, although relative risks appeared to be stronger in women, especially for stroke. In conclusion, in adults >70 years of age, CAC and CCA-IMT had similar hazard ratios for total cardiovascular disease and coronary heart disease. The CCA-IMT was more strongly related to stroke than CAC, but CAC was also a predictor of stroke.

}, keywords = {Aged, Aged, 80 and over, Carotid Artery Diseases, Carotid Artery, Common, Carotid Artery, Internal, Coronary Artery Disease, Coronary Vessels, Female, Humans, Male, ROC Curve, Severity of Illness Index, Survival Analysis, Ultrasonography, United States}, issn = {0002-9149}, doi = {10.1016/j.amjcard.2007.07.075}, author = {Newman, Anne B and Naydeck, Barbara L and Ives, Diane G and Boudreau, Robert M and Sutton-Tyrrell, Kim and O{\textquoteright}Leary, Daniel H and Kuller, Lewis H} } @article {1178, title = {Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." Dementia risk indices: A framework for identifying individuals with a high dementia risk.}, journal = {Alzheimers Dement}, volume = {6}, year = {2010}, month = {2010 Mar}, pages = {138-41}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Diagnosis, Differential, Disability Evaluation, Early Diagnosis, Humans, National Health Programs, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, United States}, issn = {1552-5279}, doi = {10.1016/j.jalz.2010.01.005}, author = {Barnes, Deborah E and Covinsky, Kenneth E and Whitmer, Rachel A and Kuller, Lewis H and Lopez, Oscar L and Yaffe, Kristine} } @article {1147, title = {CRP gene variation and risk of community-acquired pneumonia.}, journal = {Respirology}, volume = {15}, year = {2010}, month = {2010 Jan}, pages = {160-4}, abstract = {

BACKGROUND AND OBJECTIVE: CRP has several potentially antibacterial effects, and variation in the CRP gene is known to influence CRP levels. Whether this variation influences risk of infection, and hence whether CRP has anti-infective activity in humans, is uncertain.

METHODS: We evaluated a series of haplotype-tagging single nucleotide polymorphisms among 5374 individuals in the Cardiovascular Health Study, a cohort of older adults from four communities, who were followed for community-acquired pneumonia for 12-13 years. Secondarily, we evaluated whether these polymorphisms varied among men in the Health Professionals Follow-up Study who self-reported pneumonia on biennial questionnaires.

RESULTS: There were 581 (507 white and 74 black) Cardiovascular Health Study participants with incident hospitalizations for pneumonia. No single nucleotide polymorphism or haplotypes were associated with risk among white Cardiovascular Health Study participants. Among black participants, the haplotype tagged by A790T was associated with lower risk of incident pneumonia (hazard ratio 0.5; 95\% confidence interval: 0.3-0.9) and with higher CRP levels. In Health Professionals Follow-up Study, a separate haplotype was associated with less frequent self-reported pneumonia but not with circulating CRP levels.

CONCLUSIONS: Some genetic variants in CRP may be associated with risk of pneumonia, but haplotypes associated with risk are variably associated with baseline CRP levels. If CRP is a relevant component of innate immunity in humans, the inducibility or tissue-specificity of expression may be at least as important as chronic circulating levels.

}, keywords = {African Americans, Aged, Aged, 80 and over, Body Mass Index, C-Reactive Protein, Cohort Studies, Community-Acquired Infections, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Pneumonia, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Smoking}, issn = {1440-1843}, doi = {10.1111/j.1440-1843.2009.01661.x}, author = {Mukamal, Kenneth J and Pai, Jennifer K and O{\textquoteright}Meara, Ellen S and Tracy, Russell P and Psaty, Bruce M and Kuller, Lewis H and Newman, Anne B and Yende, Sachin and Curhan, Gary C and Siscovick, David S and Rimm, Eric B} } @article {6135, title = {Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment.}, journal = {Neuroimage Clin}, volume = {1}, year = {2012}, month = {2012}, pages = {179-87}, abstract = {

A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75~{\textpm}~7.1~years) scanned with brain MRI and genotyped as part of Alzheimer{\textquoteright}s Disease Neuroimaging Initiative. We carried out a replication study in an independent, non-overlapping sample of 51 elderly Caucasian subjects with MCI (mean age: 76~{\textpm}~5.5~years), scanned with brain MRI and genotyped for MTHFR, as part of the Cardiovascular Health Study. At each voxel in the brain, we tested to see where regional volume differences were associated with carrying one or more MTHFR {\textquoteright}T{\textquoteright} alleles. In ADNI subjects, carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2-8\% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5-1.5\% per T allele at 1~year follow-up, after adjusting for age and sex. We replicated these brain volume deficits of up to 5-12\% per MTHFR T allele in the independent cohort of CHS subjects. As expected, the associations weakened after controlling for homocysteine levels, which the risk gene affects. The MTHFR risk variant may thus promote brain atrophy by elevating homocysteine levels. This study aims to investigate the spatially detailed effects of this MTHFR polymorphism on brain structure in 3D, pointing to a causal pathway that may promote homocysteine-mediated brain atrophy in elderly people with MCI.

}, issn = {2213-1582}, doi = {10.1016/j.nicl.2012.09.012}, author = {Rajagopalan, Priya and Jahanshad, Neda and Stein, Jason L and Hua, Xue and Madsen, Sarah K and Kohannim, Omid and Hibar, Derrek P and Toga, Arthur W and Jack, Clifford R and Saykin, Andrew J and Green, Robert C and Weiner, Michael W and Bis, Joshua C and Kuller, Lewis H and Riverol, Mario and Becker, James T and Lopez, Oscar L and Thompson, Paul M} } @article {7348, title = {Coronary Artery Bypass Graft Surgery and Dementia Risk in the Cardiovascular Health Study.}, journal = {Alzheimer Dis Assoc Disord}, year = {2017}, month = {2017 Mar 03}, abstract = {

INTRODUCTION: The association between history of coronary artery bypass graft surgery (CABG) and dementia risk remains unclear.

METHODS: We conducted a prospective cohort analysis using data on 3155 elderly adults free from prevalent dementia from the US population-based Cardiovascular Health Study (CHS) with adjudicated incident all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia.

RESULTS: In the CHS, the hazard ratio (HR) for all-cause dementia was 1.93 [95\% confidence interval (CI), 1.36-2.74] for those with CABG history compared with those with no CABG history after adjustment for potential confounders. Similar HRs were observed for AD (HR=1.71; 95\% CI, 0.98-2.98), VaD (HR=1.42; 95\% CI, 0.56-3.65), and mixed dementia (HR=2.73; 95\% CI, 1.55-4.80). The same pattern of results was observed when these CHS findings were pooled with a prior prospective study, the pooled HRs were 1.96 (95\% CI, 1.42-2.69) for all-cause dementia, 1.71 (95\% CI, 1.04-2.79) for AD and 2.20 (95\% CI, 0.78-6.19) for VaD.

DISCUSSION: Our results suggest CABG history is associated with long-term dementia risk. Further investigation is warranted to examine the causal mechanisms which may explain this relationship or whether the association reflects differences in coronary artery disease severity.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

}, issn = {1546-4156}, doi = {10.1097/WAD.0000000000000191}, author = {Ku{\'z}ma, El{\.z}bieta and Airdrie, Jac and Littlejohns, Thomas J and Lourida, Ilianna and Thompson-Coon, Jo and Lang, Iain A and Scrobotovici, Monica and Thacker, Evan L and Fitzpatrick, Annette and Kuller, Lewis H and Lopez, Oscar L and Longstreth, William T and Ukoumunne, Obioha C and Llewellyn, David J} } @article {8382, title = {Cerebral Blood Flow Is Associated with Diagnostic Class and Cognitive Decline in Alzheimer{\textquoteright}s Disease.}, journal = {J Alzheimers Dis}, volume = {76}, year = {2020}, month = {2020}, pages = {1103-1120}, abstract = {

BACKGROUND: Reliable cerebral blood flow (CBF) biomarkers using a noninvasive imaging technique are sought to facilitate early diagnosis and intervention in early Alzheimer{\textquoteright}s disease (AD).

OBJECTIVE: We aim to identify brain regions in which CBF values are affected and related to cognitive decline in early AD using a large cohort.

METHODS: Perfusion MRIs using continuous arterial spin labeling were acquired at 1.5 T in 58 normal controls (NC), 50 mild cognitive impairments (MCI), and 40 AD subjects from the Cardiovascular Health Study Cognition Study. Regional absolute CBF and normalized CBF (nCBF) values, without and with correction of partial volume effects, were compared across three groups. Association between regional CBF values and Modified Mini-Mental State Examination (3MSE) were investigated by multiple linear regression analyses adjusted for cardiovascular risk factors.

RESULTS: After correcting for partial volume effects and cardiovascular risk factors, ADs exhibited decreased nCBF with the strongest reduction in the bilateral posterior cingulate \& precuneus region (p < 0.001) compared to NCs, and the strongest reduction in the bilateral superior medial frontal region (p < 0.001) compared to MCIs. MCIs exhibited the strongest nCBF decrease in the left hippocampus and nCBF increase in the right inferior frontal and insular region. The 3MSE scores within the symptomatic subjects were significantly associated with nCBF in the bilateral posterior and middle cingulate and parietal (p < 0.001), bilateral superior medial frontal (p < 0.001), bilateral temporoparietal (p < 0.02), and right hippocampus (p = 0.02) regions.

CONCLUSION: Noninvasive perfusion MRI can detect functional changes across diagnostic class and serve as a staging biomarker of cognitive status.

}, issn = {1875-8908}, doi = {10.3233/JAD-200034}, author = {Duan, Wenna and Sehrawat, Parshant and Balachandrasekaran, Arvind and Bhumkar, Ashish B and Boraste, Paresh B and Becker, James T and Kuller, Lewis H and Lopez, Oscar L and Gach, H Michael and Dai, Weiying} } @article {8773, title = {Cerebral Blood Flow Predicts Conversion of Mild Cognitive Impairment into Alzheimer{\textquoteright}s Disease and Cognitive Decline: An Arterial Spin Labeling Follow-up Study.}, journal = {J Alzheimers Dis}, volume = {82}, year = {2021}, month = {2021}, pages = {293-305}, abstract = {

BACKGROUND: This is the first longitudinal study to assess regional cerebral blood flow (rCBF) changes during the progression from normal control (NC) through mild cognitive impairment (MCI) and Alzheimer{\textquoteright}s disease (AD).

OBJECTIVE: We aim to determine if perfusion MRI biomarkers, derived from our prior cross-sectional study, can predict the onset and cognitive decline of AD.

METHODS: Perfusion MRIs using arterial spin labeling (ASL) were acquired in 15 stable-NC, 14 NC-to-MCI, 16 stable-MCI, and 18 MCI/AD-to-AD participants from the Cardiovascular Health Study (CHS) cognition study. Group comparisons, predictions of AD conversion and time to conversion, and Modified Mini-Mental State Examination (3MSE) from rCBF were performed.

RESULTS: Compared to the stable-NC group: 1) the stable-MCI group exhibited rCBF decreases in the right temporoparietal (p = 0.00010) and right inferior frontal and insula (p = 0.0094) regions; and 2) the MCI/AD-to-AD group exhibited rCBF decreases in the bilateral temporoparietal regions (p = 0.00062 and 0.0035). Compared to the NC-to-MCI group, the stable-MCI group exhibited a rCBF decrease in the right hippocampus region (p = 0.0053). The baseline rCBF values in the posterior cingulate cortex (PCC) (p = 0.0043), bilateral superior medial frontal regions (BSMF) (p = 0.012), and left inferior frontal (p = 0.010) regions predicted the 3MSE scores for all the participants at follow-up. The baseline rCBF in the PCC and BSMF regions predicted the conversion and time to conversion from MCI to AD (p < 0.05; not significant after multiple corrections).

CONCLUSION: We demonstrated the feasibility of ASL in detecting rCBF changes in the typical AD-affected regions and the predictive value of baseline rCBF on AD conversion and cognitive decline.

}, issn = {1875-8908}, doi = {10.3233/JAD-210199}, author = {Duan, Wenna and Zhou, Grace D and Balachandrasekaran, Arvind and Bhumkar, Ashish B and Boraste, Paresh B and Becker, James T and Kuller, Lewis H and Lopez, Oscar L and Gach, H Michael and Dai, Weiying} }