@article {1434, title = {Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {139}, year = {1994}, month = {1994 Jun 15}, pages = {1164-79}, abstract = {

The prevalence of subclinical atherosclerosis and cardiovascular disease was evaluated among the 5,201 adults aged > or = 65 years in four communities participating in the Cardiovascular Health Study from June 1989 through May 1990. A combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication defined subclinical disease. The prevalence of subclinical disease was 36\% in women and 38.7\% in men and increased with age. Among women, low-density lipoprotein cholesterol, systolic blood pressure, blood glucose, and cigarette smoking were positively associated, and high-density lipoprotein cholesterol negatively associated, with subclinical disease. In men, systolic blood pressure, blood glucose, and cigarette smoking were independent risk factors in multiple logistic regression analyses. The risk factors for subclinical disease are, therefore, similar to those for clinical disease at younger ages, especially among women. It is possible that older individuals with subclinical disease are at very high risk of developing clinical disease and that more aggressive interventions to prevent clinical disease should be oriented to individuals with subclinical disease.

}, keywords = {Aged, Aged, 80 and over, Arteriosclerosis, Cardiovascular Diseases, Female, Humans, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, United States}, issn = {0002-9262}, author = {Kuller, L and Borhani, N and Furberg, C and Gardin, J and Manolio, T and O{\textquoteright}Leary, D and Psaty, B and Robbins, J} } @article {1496, title = {Differences in prevalence of and risk factors for subclinical vascular disease among black and white participants in the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {18}, year = {1998}, month = {1998 Feb}, pages = {283-93}, abstract = {

A composite measure of subclinical vascular disease has been developed in the Cardiovascular Health Study (CHS). In previous reports, we measured the prevalence of subclinical disease among the original 5201 participants in the CHS, the relationship of risk factors to subclinical disease, and the association of subclinical disease to clinical coronary heart disease. In 1992 to 1993 (year 4 of the study), a larger cohort of 424 black women and 248 black men was added to the study. In this study, we have compared the prevalence of subclinical disease among blacks and whites in the CHS and the association with cardiovascular risk factors. The prevalence of subclinical disease for all participants (aged > or =65 years) was 41.3\% for white women, 39.7\% for black women, 41.9\% for white men, and 43.7\% for black men. The prevalence increased with age. The risk factor associations for subclinical disease were similar among blacks and whites. In multivariate analysis, age, systolic blood pressure, LDL cholesterol, smoking, and family history of myocardial infarction were independently associated with subclinical disease among both black and white women, while for white men, systolic blood pressure, use of antihypertensive medication, smoking, body mass index, and diastolic blood pressure (inverse) were related to subclinical disease. In black men, blood triglyceride level, use of antihypertensive medications, and family history of myocardial infarction (inverse) were associated with subclinical disease.

}, keywords = {African Americans, Aged, Cardiovascular Physiological Phenomena, Cohort Studies, European Continental Ancestry Group, Female, Health Status, Humans, Male, Multivariate Analysis, Prevalence, Regression Analysis, Risk Factors, Vascular Diseases}, issn = {1079-5642}, author = {Kuller, L and Fisher, L and McClelland, R and Fried, L and Cushman, M and Jackson, S and Manolio, T} } @article {597, title = {The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.}, journal = {JAMA}, volume = {282}, year = {1999}, month = {1999 Jul 07}, pages = {40-6}, abstract = {

CONTEXT: Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD.

OBJECTIVES: To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline.

DESIGN: The Cardiovascular Health Study, a population-based, prospective cohort study.

SETTING AND POPULATION: A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively.

MAIN OUTCOME MEASURES: Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus.

RESULTS: Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele.

CONCLUSIONS: Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.

}, keywords = {Aged, Aging, Alleles, Apolipoproteins E, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Diabetes Mellitus, Genotype, Humans, Mental Status Schedule, Prospective Studies, Risk Factors}, issn = {0098-7484}, doi = {10.1001/jama.282.1.40}, author = {Haan, M N and Shemanski, L and Jagust, W J and Manolio, T A and Kuller, L} } @article {624, title = {Cognitive test performance and presence of subclinical cardiovascular disease in the cardiovascular health study.}, journal = {Neuroepidemiology}, volume = {19}, year = {2000}, month = {2000 Nov-Dec}, pages = {312-9}, abstract = {

The purpose of the present study was to investigate the relationship between performance on a comprehensive battery of neuropsychological tests and the presence of clinical, subclinical or no cardiovascular disease in an elderly community-dwelling population. The results confirm previous reports of significant associations of age, education and gender with test performance. When performance was examined controlling for these variables, significant associations of disease group were seen with five measures emphasizing speed of performance; Parts A and B of the Trail Making Test, the WAIS-R Digit Symbol and Block Design subtests and category verbal fluency. These results add to the evidence that, in addition to other health implications, cardiovascular disease is related to cognitive functioning in the elderly even at subclinical levels.

}, keywords = {Aged, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Hypertension, Male, Severity of Illness Index, Wechsler Scales}, issn = {0251-5350}, doi = {10.1159/000026270}, author = {Saxton, J and Ratcliff, G and Newman, A and Belle, S and Fried, L and Yee, J and Kuller, L} } @article {617, title = {Estrogen use, APOE, and cognitive decline: evidence of gene-environment interaction.}, journal = {Neurology}, volume = {54}, year = {2000}, month = {2000 May 23}, pages = {1949-54}, abstract = {

OBJECTIVE: APOE-epsilon4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE-epsilon4 and cognitive decline.

METHOD: - As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (> or =65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on > or =2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening.

RESULTS: A total of 297 (11\%) women were current estrogen users and 336 (12\%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points (p = 0.023). Compared with epsilon4-negative women, epsilon4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS < 80), hazard risk [HR] = 1.47; 95\% CI, 1.13 to 1.90. There was an interaction between estrogen use and epsilon4 presence (p = 0.037). Among epsilon4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95\% CI, 0.36 to 0.99), whereas, it did not reduce the risk among epsilon4-positive women (current use, HR = 1.33; 95\% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in epsilon4-negative women but not in epsilon4-positive women (p for interaction < 0.05 for both). Differences remained after adjusting for age, education, race, and stroke.

CONCLUSIONS: Estrogen use was associated with less cognitive decline among epsilon4-negative women but not epsilon4-positive women. Potential mechanisms, including carotid atherosclerosis, by which epsilon4 may interact with estrogen and cognition warrant further investigation.

}, keywords = {Aged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Carotid Stenosis, Estrogen Replacement Therapy, Female, Genotype, Humans, Mental Status Schedule, Neuropsychological Tests, Risk Factors}, issn = {0028-3878}, doi = {10.1212/wnl.54.10.1949}, author = {Yaffe, K and Haan, M and Byers, A and Tangen, C and Kuller, L} } @article {641, title = {Normative data on the Boston Naming Test and two equivalent 30-item short forms.}, journal = {Clin Neuropsychol}, volume = {14}, year = {2000}, month = {2000 Nov}, pages = {526-34}, abstract = {

Because of the significance of the Boston Naming Test (BNT) in the differential diagnosis of the dementias, especially Alzheimer{\textquoteright}s disease, adequate norms from community-dwelling elderly individuals are essential. The present study describes the development of two new empirically derived equivalent short forms (30 items each) of the test. Normative data for the total BNT and the two equivalent 30-item halves based on item difficulty are presented using the performance of 314 community-dwelling individuals aged 65 and over. Age and education norms are presented using an overlapping midpoint interval strategy.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Neuropsychological Tests, Population Surveillance, Reference Values}, issn = {1385-4046}, doi = {10.1076/clin.14.4.526.7204}, author = {Saxton, J and Ratcliff, G and Munro, C A and Coffey, E C and Becker, J T and Fried, L and Kuller, L} } @article {663, title = {Silent MRI infarcts and the risk of future stroke: the cardiovascular health study.}, journal = {Neurology}, volume = {57}, year = {2001}, month = {2001 Oct 09}, pages = {1222-9}, abstract = {

BACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the elderly.

OBJECTIVE: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors.

METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts.

RESULTS: Approximately 28\% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes).

CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow- up in older individuals without a clinical history of stroke.

}, keywords = {Aged, Cerebral Infarction, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Magnetic Resonance Imaging, Male, Predictive Value of Tests, Risk Factors, Stroke}, issn = {0028-3878}, doi = {10.1212/wnl.57.7.1222}, author = {Bernick, C and Kuller, L and Dulberg, C and Longstreth, W T and Manolio, T and Beauchamp, N and Price, T} } @article {815, title = {Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Dec 28}, pages = {2341-7}, abstract = {

OBJECTIVE: To determine if individuals ultimately diagnosed with Alzheimer disease (AD) exhibited evidence of cognitive impairment on neuropsychological tests administered between 1.5 years and 8.1 years before dementia onset.

METHODS: A total of 693 community-dwelling individuals, part of the Cardiovascular Health Study, completed a neuropsychological test battery in 1991/92. Subjects were followed annually over the next 8 years (median follow-up = 7.4 years). Seventy-two individuals were ultimately diagnosed with AD (median follow-up = 4.5 years): 24 with AD onset 1.5 to 3.4 years after baseline neuropsychological testing, 20 with AD onset 3.5 to 5.0 years after testing, and 28 with onset 5.1 to 8.1 years after testing. A total of 621 individuals remained nondemented throughout the 8 years of follow-up (median follow-up = 7.5 years).

RESULTS: Subjects ultimately diagnosed with AD had poorer scores on baseline neuropsychological measures than subjects who remained nondemented. Although individuals closest to AD onset (i.e., 1.5 to 3.4 years) performed the most poorly, cognitive impairment was detected in individuals who did not develop AD until 5 to 8 years later.

CONCLUSIONS: Cognitive changes can be detected well before onset of Alzheimer disease.

}, keywords = {Age of Onset, Alzheimer Disease, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Confounding Factors, Epidemiologic, Disease Progression, Early Diagnosis, Educational Status, Female, Follow-Up Studies, Humans, Male, Memory Disorders, Neuropsychological Tests, Predictive Value of Tests, Proportional Hazards Models, Risk, Sensitivity and Specificity, Time Factors}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000147470.58328.50}, author = {Saxton, J and Lopez, O L and Ratcliff, G and Dulberg, C and Fried, L P and Carlson, M C and Newman, A B and Kuller, L} } @article {832, title = {Morphometric analysis of gray matter volume in demented older adults: exploratory analysis of the cardiovascular health study brain MRI database.}, journal = {Neuroepidemiology}, volume = {24}, year = {2005}, month = {2005}, pages = {221-9}, abstract = {

We tested the feasibility of a fully automated brain MRI voxel count technique--automated labeling pathway (ALP)--in a sample of 15 demented and 13 cognitively normal women (age 75-85 years) participating to the Cardiovascular Health Study (CHS). We hypothesized that ALP would replicate well-established findings of the anatomical correlates of dementia. In particular, we hypothesized that ALP volumetric measures would: (1) significantly differ between cognitively normal and demented women in those brain areas that are established markers for diagnosis of dementia (temporal and medial temporal lobes, hippocampus, amygdala and parahippocampus) but not in other brain areas (e.g., occipital lobe, visual cortex, motor cortex) and (2) correlate with visual ratings of brain disease which have been previously collected as part of the CHS. ALP required minimal operator intervention (input of brain images and verification of misalignments) and employed computer time of about 1 h per brain. ALP detected significant focal volumetric differences in the limbic system (p values between groups for hippocampus and parahippocampus: 0.002 and 0.005, respectively), temporal lobe (p < 0.0001) and caudate (p = 0.009), but not in other brain areas (e.g. occipital lobe, visual or motor cortex). Furthermore, ALP measures of medial temporal lobe atrophy strongly correlated with CHS visual ratings of ventricular enlargement (r(2) = 0.6, p = 0.002 for medial temporal lobe). In conclusion, ALP-detected focal brain atrophy was strongly associated with dementia. Because of its fully automated design, ALP technique is an ideal candidate to assess whether volumetric measures of specific areas can discriminate dementia better than currently available measures of global brain atrophy in large epidemiological studies.

}, keywords = {Aged, Aged, 80 and over, Brain, Dementia, Educational Status, Feasibility Studies, Female, Health Status, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Organ Size, Reproducibility of Results}, issn = {0251-5350}, doi = {10.1159/000085140}, author = {Rosano, C and Becker, J and Lopez, O and Lopez-Garcia, P and Carter, C S and Newman, A and Kuller, L and Aizenstein, H} } @article {869, title = {Statins and cognitive function in the elderly: the Cardiovascular Health Study.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1388-94}, abstract = {

OBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults.

METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy.

RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups.

CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.

}, keywords = {Aged, Aged, 80 and over, Aging, Anticholesteremic Agents, Atrophy, Brain, Cholesterol, Cognition Disorders, Cohort Studies, Dementia, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Longitudinal Studies, Male, Memory Disorders, Nootropic Agents, Treatment Outcome}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000182897.18229.ec}, author = {Bernick, C and Katz, R and Smith, N L and Rapp, S and Bhadelia, R and Carlson, M and Kuller, L} } @article {984, title = {The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.}, journal = {Eur J Epidemiol}, volume = {22}, year = {2007}, month = {2007}, pages = {839-69}, abstract = {

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

}, keywords = {Albumins, Biomarkers, Cardiovascular Diseases, Databases, Factual, Far East, Humans, Inflammation, Leukocyte Count, Lipids, Lipoproteins, HDL, Prospective Studies, Risk Factors, Triglycerides}, issn = {0393-2990}, doi = {10.1007/s10654-007-9165-7}, author = {Danesh, J and Erqou, S and Walker, M and Thompson, S G and Tipping, R and Ford, C and Pressel, S and Walldius, G and Jungner, I and Folsom, A R and Chambless, L E and Knuiman, M and Whincup, P H and Wannamethee, S G and Morris, R W and Willeit, J and Kiechl, S and Santer, P and Mayr, A and Wald, N and Ebrahim, S and Lawlor, D A and Yarnell, J W G and Gallacher, J and Casiglia, E and Tikhonoff, V and Nietert, P J and Sutherland, S E and Bachman, D L and Keil, J E and Cushman, M and Psaty, B M and Tracy, R P and Tybjaerg-Hansen, A and Nordestgaard, B G and Frikke-Schmidt, R and Giampaoli, S and Palmieri, L and Panico, S and Vanuzzo, D and Pilotto, L and Simons, L and McCallum, J and Friedlander, Y and Fowkes, F G R and Lee, A J and Smith, F B and Taylor, J and Guralnik, J and Phillips, C and Wallace, R and Blazer, D and Khaw, K T and Jansson, J H and Donfrancesco, C and Salomaa, V and Harald, K and Jousilahti, P and Vartiainen, E and Woodward, M and D{\textquoteright}Agostino, R B and Wolf, P A and Vasan, R S and Pencina, M J and Bladbjerg, E M and Jorgensen, T and Moller, L and Jespersen, J and Dankner, R and Chetrit, A and Lubin, F and Rosengren, A and Wilhelmsen, L and Lappas, G and Eriksson, H and Bjorkelund, C and Cremer, P and Nagel, D and Tilvis, R and Strandberg, T and Rodriguez, B and Bouter, L M and Heine, R J and Dekker, J M and Nijpels, G and Stehouwer, C D A and Rimm, E and Pai, J and Sato, S and Iso, H and Kitamura, A and Noda, H and Goldbourt, U and Salomaa, V and Salonen, J T and Nyyss{\"o}nen, K and Tuomainen, T-P and Deeg, D and Poppelaars, J L and Meade, T and Cooper, J and Hedblad, B and Berglund, G and Engstrom, G and D{\"o}ring, A and Koenig, W and Meisinger, C and Mraz, W and Kuller, L and Selmer, R and Tverdal, A and Nystad, W and Gillum, R and Mussolino, M and Hankinson, S and Manson, J and De Stavola, B and Knottenbelt, C and Cooper, J A and Bauer, K A and Rosenberg, R D and Sato, S and Naito, Y and Holme, I and Nakagawa, H and Miura, H and Ducimetiere, P and Jouven, X and Crespo, C and Garcia-Palmieri, M and Amouyel, P and Arveiler, D and Evans, A and Ferrieres, J and Schulte, H and Assmann, G and Shepherd, J and Packard, C and Sattar, N and Cantin, B and Lamarche, B and Despr{\'e}s, J-P and Dagenais, G R and Barrett-Connor, E and Wingard, D and Bettencourt, R and Gudnason, V and Aspelund, T and Sigurdsson, G and Thorsson, B and Trevisan, M and Witteman, J and Kardys, I and Breteler, M and Hofman, A and Tunstall-Pedoe, H and Tavendale, R and Lowe, G D O and Ben-Shlomo, Y and Howard, B V and Zhang, Y and Best, L and Umans, J and Onat, A and Meade, T W and Njolstad, I and Mathiesen, E and Lochen, M L and Wilsgaard, T and Gaziano, J M and Stampfer, M and Ridker, P and Ulmer, H and Diem, G and Concin, H and Rodeghiero, F and Tosetto, A and Brunner, E and Shipley, M and Buring, J and Cobbe, S M and Ford, I and Robertson, M and He, Y and Ibanez, A M and Feskens, E J M and Kromhout, D and Collins, R and Di Angelantonio, E and Kaptoge, S and Lewington, S and Orfei, L and Pennells, L and Perry, P and Ray, K and Sarwar, N and Scherman, M and Thompson, A and Watson, S and Wensley, F and White, I R and Wood, A M} } @article {1155, title = {Cancer linked to Alzheimer disease but not vascular dementia.}, journal = {Neurology}, volume = {74}, year = {2010}, month = {2010 Jan 12}, pages = {106-12}, abstract = {

OBJECTIVE: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD).

METHODS: Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study-Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer.

RESULTS: The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95\% confidence interval [CI] = 0.20-0.84) and pure AD (HR = 0.31, 95\% CI = 0.12-0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95\% CI = 0.52-0.997) and pure AD (HR = 0.57; 95\% CI = 0.36-0.90) among white subjects after adjustment for demographics, number of APOE epsilon4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD.

CONCLUSIONS: In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Cohort Studies, Dementia, Vascular, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Hospitalization, Humans, Male, Neoplasms, Nerve Degeneration, Parkinson Disease, Prevalence, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e3181c91873}, author = {Roe, C M and Fitzpatrick, A L and Xiong, C and Sieh, W and Kuller, L and Miller, J P and Williams, M M and Kopan, R and Behrens, M I and Morris, J C} }