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Original Contribution |

Association of Incident Alzheimer Disease and Blood Pressure Measured From 13 Years Before to 2 Years After Diagnosis in a Large Community Study FREE

Martha Clare Morris, ScD; Paul A. Scherr, PhD, ScD; Liesi E. Hebert, ScD; Robert J. Glynn, PhD; David A. Bennett, MD; Denis A. Evans, MD
[+] Author Affiliations

From the Rush Institute for Healthy Aging (Drs Morris, Hebert, Bennett, and Evans) and Rush Alzheimer's Disease Center (Drs Bennett and Evans), and the Departments of Internal Medicine (Drs Morris, Hebert, and Evans), Preventive Medicine (Dr Morris), and Neurological Sciences (Drs Bennett and Evans), Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill; the Health Care and Aging Studies Branch, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Scherr); and the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (Dr Glynn).


Arch Neurol. 2001;58(10):1640-1646. doi:10.1001/archneur.58.10.1640.
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Published online

Background  It is uncertain whether high blood pressure increases the risk of developing Alzheimer disease (AD).

Objective  To examine the association between incident AD and blood pressure measured up to 13 years before diagnosis.

Design  Longitudinal cohort study conducted from 1982 to 1988, with blood pressure measured every 3 years in home interviews, and in 1973 for a portion (60%) of the sample.

Setting  Community of East Boston, Mass.

Participants  Six hundred thirty-four subjects 65 years or older and without AD were selected as a stratified random sample of participants of the East Boston Established Populations for Epidemiologic Studies of the Elderly.

Main Outcome Measure  Alzheimer disease was diagnosed by a neurologist using a structured clinical evaluation.

Results  High blood pressure was not associated with an increased risk of AD in logistic regression models adjusted for age, sex, and level of education. There was no association with systolic pressure measured 13 years before diagnosis (odds ratio = 1.03/10 mm Hg; 95% confidence interval, 0.80-1.32) and an inverse association with systolic pressure measured 4 years before diagnosis (odds ratio = 0.82/10 mm Hg; 95% confidence interval, 0.72-0.95). Associations for diastolic pressure were in the same direction as those for systolic pressure except with wider confidence intervals. The odds ratios were not materially different with further adjustment for cardiovascular risk factors and diseases.

Conclusion  In this large community study, high blood pressure was not associated with an increased risk of AD.

Figures in this Article

SEVERAL STUDIES raise the possibility that high blood pressure may increase the risk of Alzheimer disease (AD),1,2 and many have reported decreased cognitive performance36 and greater cognitive decline3,710 with age among persons with high blood pressure. Neuroimaging studies show associations between the presence of white matter lesions or brain atrophy and a history of high blood pressure,1121 AD,2224 cerebrovascular disease,13,18,25 or cognitive impairment.12,1416,20,26 Few studies have directly tested whether high blood pressure increases the risk of incident AD, and these have conflicting results of no association27 and increased risk.28,29 One of these studies reported a decline in blood pressure beginning several years before disease onset in subjects with dementia, suggesting that the disease process may lower blood pressure levels.28 We examined the relationship between incident AD and blood pressure measured from 13 years before to 2 years after diagnosis in a large population-based study.

STUDY POPULATION

The study of risk factors for AD was conducted in a sample of participants from the East Boston Established Populations for Epidemiologic Studies of the Elderly (EPESE).30 Between 1982 and 1983, as part of the EPESE study, all persons 65 years and older residing in East Boston, Mass, were contacted for a home interview. A total of 3809 (85%) age-eligible residents participated, and all survivors were recontacted for home follow-up interviews approximately 3 and 6 years later.

At baseline, 2313 persons were determined to be free of AD either by direct clinical examination (n = 177) or by good memory performance at the initial interview (n = 2136).31 In a clinically evaluated sample of the population, 97% of the good memory performers were found to be unaffected with AD.32

From 1985 to 1986, participants were reinterviewed in their homes, and a random sample of 642 persons from the disease-free cohort (stratified by age, sex, and change in cognitive performance) was clinically evaluated for incident AD (Figure 1).

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Figure 1.

Sample design of the East Boston study (East Boston, Mass) of incident Alzheimer disease. EPESE indicates Established Populations for Epidemiologic Studies of the Elderly.

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BLOOD PRESSURE MEASUREMENT

Blood pressure was measured at 4 different time points: a mean of 13.6 years before evaluation for incident AD, 4.5 years before evaluation, 1.5 years before evaluation, and 2 years after diagnosis. The latter 3 measurement periods were part of the EPESE population interviews. The first set of measurements were obtained in 1973 for 378 persons aspart of a community blood pressure screening for the Hypertension Detection and Follow-Up Program (HDFP).33 Among sample participants younger than 80 years, 72% underwent HDFP blood pressure screening (participants 80 years and older were not eligible for the HDFP). Measurements were available for 634 sample participants at baseline, 612 participants at the 3-year follow-up, and 426 participants (67%) at the 6-year follow-up (Table 1).

Table Graphic Jump LocationTable 1 Blood Pressure Measurements Among 642 Persons Evaluated for Incident AD*

All blood pressure measurements were obtained in participants' homes according to the HDFP protocol. On each occasion, blood pressure was measured 3 consecutive times with 30 seconds between measurements using mercury sphygmomanometers on seated subjects with the arm resting at heart level. For analyses of each time point, the average of the 3 blood pressure measurements was used. A more detailed description of the blood pressure procedures has been published previously.34 All interviewers passed a written test, a videotaped test of blood pressure readings, and live practice tests with a supervisor using a split stethoscope. The overall mean of blood pressure readings by trainees had to be within ±1.96 mm Hg of the standard mean on the videotaped test.35 Data from the HDFP on blinded duplicate blood pressure readings demonstrated good reproducibility of trainee readings.

DIAGNOSIS OF AD

The clinical evaluations included a neurological examination, neuropsychological performance testing, a medical history, and a brief psychiatric evaluation. The definition of probable AD was based on criteria consistent with the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association.36 We modified the definition to include persons who met the criteria for probable AD and who had a coexisting dementing condition to prevent the possibility of a protective association due to the classification system (for example, if high blood pressure levels were associated with an increased risk of vascular dementia). A more complete description of sampling for incident AD and of the clinical evaluation was published previously.31,37

COVARIATES

All covariates except for clinical stroke and antihypertensive medication use at HDFP were based on data from the EPESE baseline interview. History of hypertension was self-reported. Heart disease was defined as a self-reported history of myocardial infarction, the use of digitalis or loop diuretics, or evidence of angina pectoris based on participant responses to the London School of Hygiene Cardiovascular Questionnaire.38 Diabetes was defined as the use of antidiabetic medication or a participant report of clinically diagnosed "diabetes, sugar in the urine, or high blood sugar." Body mass index was computed as weight in kilograms divided by height in meters squared using self-reported height and weight. The use of digitalis, antihypertensives, and diabetic medications was determined by interviewer inspection of all medications taken within the previous 2 weeks. Clinical stroke was based on medical history and examination by a neurologist at the clinical evaluation. The presence of the apolipoprotein E ϵ4 allele (APOE*E4) was based on the genotyping of blood obtained at the clinical evaluation. DNA was extracted from blood specimens stored at −70°C for periods ranging from 7 to 12 years, and genotyping was carried out according to the method described by Hixson and Vernier.39 Indicator variables at the HDFP for current and past use of antihypertensive medications were based on participant self-report.

STATISTICAL ANALYSIS

We used logistic regression to examine the association between AD and blood pressure measured at the 4 different time points. Blood pressure was modeled both continuously and categorically using a priori defined categories.7 Basic-adjusted models included the following covariates: sex, age (continuous in years), level of education (continuous in years), and interval (number of days from the determination of disease-free status to clinical evaluation for incident AD). All models were adjusted for the stratified random sampling using SUDAAN statistical software (Research Triangle Institute, Research Triangle Park, NC). Multiple-adjusted models included covariates from the basic model plus other covariates, entered both individually and in all combinations. The covariates included indicator variables for APOE*E4 (any ϵ4 allele vs none), clinical stroke, history of hypertension, heart disease, antihypertensive medication use, and diabetes, and a continuous variable for body mass index. Effect modification was examined for all covariates by including interaction terms of the covariate and blood pressure in the basic-adjusted model and by examining the blood pressure association with AD within levels of each covariate. Pulse pressures were computed as the difference between the mean systolic and diastolic pressures at each time point.

For graphic display of blood pressure across time, all blood pressure measurements were adjusted to the age and sex distribution at baseline. An individual's adjusted value equaled the actual value minus the expected value for that individual's sex and age based on linear regression models. The mean blood pressure levels at baseline (142/76 mm Hg) were added to these residuals for a more intuitive presentation.

DESCRIPTION OF THE STUDY SAMPLE

There were 99 cases of incident AD in the study sample, including 5 subjects who had a coexisting dementing disease. The estimated annual incidence of AD increased strongly with age, from 0.6% among persons 65 to 69 years of age to 8.4% among persons 85 years and older.31 The mean blood pressure level for the sample was 142/76 mm Hg. One hundred thirty-six subjects (21%) had a baseline systolic pressure reading of 160 mm Hg or greater, and 8.9% had a diastolic pressure reading of 90 mm Hg or greater. Compared with persons who had lower blood pressure, subjects with a systolic pressure reading of 160 mm Hg or higher were older and were more likely to have conditions associated with cardiovascular disease, including a history of hypertension, stroke, heart disease, and diabetes (Table 2). Participants with a diastolic pressure reading greater than 90 mm Hg were more likely than those with low diastolic pressure to be male and to have a history of hypertension.

Table Graphic Jump LocationTable 2 Baseline Characteristics by Level of Baseline Blood Pressure of 634 Participants Who Were Clinically Evaluated for Incident Alzheimer Disease, East Boston, Mass, 1982-1985*
BLOOD PRESSURE MEASURED 4 YEARS BEFORE DIAGNOSIS

Systolic and diastolic blood pressures measured 4 years previously for 634 persons were inversely associated with incident AD in logistic models adjusted for age, sex, educational level, and interval to diagnosis. The association with systolic pressure was linear and statistically significant (odds ratio [OR] = 0.82/10 mm Hg increase; 95% confidence interval [CI], 0.72-0.95) (Table 3). In categorical analyses, compared with the reference level of 130 to 139 mm Hg, the risk of incident AD was lower in the group with a systolic pressure reading of 160 mm Hg or greater (OR = 0.29; 95% CI, 0.10-0.86) and nearly equivalent for subjects with a systolic pressure reading less than 130 mm Hg (OR = 0.87; 95% CI, 0.37-2.06). The association with diastolic pressure was also linear and inverse but only marginally significant (OR = 0.74/10 mm Hg increase; 95% CI, 0.53-1.01). The risk of AD was not significantly different from the reference level of 80 to 89 mm Hg for diastolic pressure readings of 90 mm Hg or greater (OR = 0.74; 95% CI, 0.23-2.40) or for those less than 70 mm Hg (OR = 1.81; 95% CI, 0.77-4.29).

Table Graphic Jump LocationTable 3 Basic-Adjusted and Multiple-Adjusted ORs and 95% CIs for 4-Year Risk of Incident AD for Blood Pressure Measured Continuously (10–mm Hg Increments) and Categorically, East Boston Study (East Boston, Mass), 1982-1988*

The ORs did not change materially with further adjustment for other covariates including APOE*E4, body mass index, or history of hypertension, heart disease, clinical stroke, or diabetes (Table 3); there was also no evidence of effect modification by these covariates. A self-reported history of hypertension was not associated with incident AD in the basic-adjusted model (OR = 1.13; 95% CI, 0.60-2.13).

ANTIHYPERTENSIVE MEDICATION USE

We considered that the inverse association between blood pressure and AD could be due to treatment with antihypertensive medications. In the basic-adjusted model, incident AD was not associated with the use of these medications or with any specific type of antihypertensive medication (Table 4). There was no evidence of interactive effects of these medications with blood pressure on the risk of AD.

Table Graphic Jump LocationTable 4 ORs and 95% CIs for 4-Year Risk of Incident AD by Antihypertensive Medication Use and Level of Systolic Pressure Based on Logistic Regression Models Adjusted for Age, Sex, and Level of Education, East Boston Study (East Boston, Mass), 1982-1988*
PULSE PRESSURE

Pulse pressure measured 4 years prior to the clinical evaluation had a marginally significant inverse association with the risk of AD (OR = 0.85/10–mm Hg increase in pulse pressure; 95% CI, 0.70-1.02). Compared with the reference pulse pressure of 60 to 69 mm Hg, the ORs for incident AD were as follows: 0.97 for subjects with a pulse pressure reading less than 50 mm Hg, 2.1 for those with a reading between 50 and 59 mm Hg, 0.77 for a level between 70 and 79 mm Hg, and 0.66 for 80 mm Hg or higher.

BLOOD PRESSURE MEASURED 13 YEARS BEFORE DIAGNOSIS

Blood pressure measured 13 years before diagnosis had no association with incident AD. The 378 subjects in this analysis were as young as 54 years at the time of blood pressure measurement and between the ages of 69 and 80 years at the clinical evaluation for incident AD (41 were diagnosed with incident AD). In basic-adjusted models, the ORs for AD were 1.03/10–mm Hg increase in systolic pressure (95% CI, 0.80-1.32) and 1.16/10–mm Hg increase in diastolic pressure (95% CI, 0.75-1.81) (Table 5). There was no increased risk of AD for persons with blood pressures in the hypertensive range. Compared with lower levels, the OR for subjects with a systolic pressure reading of 160 mm Hg or greater was 1.13 (95% CI, 0.24-5.37) and for those with a diastolic pressure reading of 90 mm Hg or higher, 1.56 (95% CI, 0.46-5.32) (Table 5). Further adjustment for current use of antihypertensive medications or any other covariates from the baseline interview did not materially change the results.

Table Graphic Jump LocationTable 5 ORs and 95% CIs of Incident AD by Level of Systolic and Diastolic Blood Pressure Measured 13 Years Earlier Among 378 Participants in the East Boston Study (East Boston, Mass), 1973-1988*
HYPERTENSIVE LEVELS AT BOTH MEASUREMENT POINTS

Of the 378 persons who had their blood pressure measured at both 13 and 4 years before the clinical evaluation for incident AD, 44 had blood pressure levels consistently in the hypertensive range of 160 mm Hg or greater for systolic pressure or 90 mm Hg or higher for diastolic pressure. Of the remainder, 98 subjects had consistently normal blood pressure readings (<140/<85 mm Hg), and 236 persons had mixed (≥160 mm Hg or ≥90 mm Hg at 1 time point only) or high-normal (systolic, 140-159 mm Hg; diastolic, 85-89 mm Hg) blood pressure readings at the 2 time points. In basic-adjusted models, relative to the normotensive subjects (<140/<85 mm Hg), the risk of incident AD was not significantly different in the chronically hypertensive group (OR = 1.10; 95% CI, 0.19-6.44) or the mixed/high-normal group (OR = 0.92; 95% CI, 0.39-2.20).

BLOOD PRESSURE MEASURED 2 YEARS AFTER DIAGNOSIS

We also found no association between incident AD and blood pressure measured 2 years following diagnosis among 426 participants who survived until the 6-year follow-up interview and had their blood pressure measured (39 of whom had AD). The OR for systolic blood pressure was 1.06/10–mm Hg increase (95% CI, 0.86-1.32) and for diastolic pressure, 1.42/10–mm Hg increase (95% CI, 0.96-2.10) in the basic-adjusted model.

BLOOD PRESSURE LEVELS ACROSS TIME BY AD STATUS

Figure 2 presents age- and sex-adjusted mean blood pressure levels for 1973 through 1988 according to a diagnosis of AD in 1986. After adjustment for age, blood pressure level varied little by AD status during more than 15 years of observation. The differences were even smaller when the means were restricted to the 288 persons with blood pressure measurements at all 4 time points.

Place holder to copy figure label and caption
Figure 2.

Mean blood pressure levels, adjusted for age and sex, from 13 years before clinical evaluation to 2 years after for persons affected (solid line) and unaffected (dotted line) with incident Alzheimer disease.

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In our study, there was little association between blood pressure levels during 15 years of observation and risk of AD. There was no evidence of increased risk of AD among persons with high blood pressure 13 years before disease onset, an inverse association for blood pressure measured 4 years before diagnosis, and no effect of AD on blood pressure measured 2 years after the diagnosis. The inverse association between blood pressure measured 4 years previously and risk of AD is puzzling. The pathogenic mechanism for any protective effect is unclear, and we had no prior hypothesis of an inverse association. Together with the lack of association between disease risk and blood pressure measurements at other times, these data suggest that this inverse association at 1 time point may be due to chance.

The estimated ORs were adjusted for important confounders that were previously associated with incident AD in the East Boston population, including age,31 level of education,40 and APOE*E4.41 Longitudinal follow-up of a community population, as was done in the East Boston study, offers several advantages in the evaluation of high blood pressure as a risk factor for AD. Cases of AD are identified by structured, uniform clinical evaluation of a random sample of the population at risk, reducing the potential for biased results. Blood pressure measurement 4 to 13 years before diagnosis more clearly establishes blood pressure as a cause rather than an effect of the disease, and using the mean of multiple blood pressure measurements at each time point increases the likelihood of capturing the true underlying blood pressure. The large number of AD cases allowed for a more accurate estimation of the 4-year risk of disease. One limitation of the study was the small number of participants with very high blood pressure. Another limitation was the unavailability of blood pressure measurements for about a third of participants, both 13 years before diagnosis and 2 years after diagnosis. The fewer cases of AD at these time points resulted in wide 95% CIs that included small to moderate ORs reported in a previous study.29 Analysis of the data suggests that the estimated ORs for the earlier blood pressure levels are not likely to be biased. Adjusting for age, sex, and educational level, the risk of AD was not significantly different for persons who did and did not have HDFP blood pressure measurements, and the associations between AD and baseline blood pressures were the same for the 2 groups. Participants without blood pressure measurements at the sixth follow-up interview (of whom 50% had died) were more likely to have been diagnosed with AD than those analyzed, and had higher mean levels of systolic pressure at baseline (148 vs 144 mm Hg, respectively). The unavailability of blood pressure measurements for some of the survivors may have biased the observed associations with subsequent blood pressures.

Few prospective studies have examined whether high blood pressure increases the risk of developing AD. One longitudinal study showed higher initial blood pressure levels among 10 persons who developed AD compared with those who remained unaffected during 15 years of follow-up.28 Another found a greater risk of dementia and AD with a high diastolic pressure in middle age, but only among men who had never been treated.29 Although one study found no association between high blood pressure and a 7-year incidence of AD,27 it did observe a statistically significant increased risk of vascular dementia as the level of systolic pressure increased (OR = 1.98/1-SD increase in systolic mm Hg).

There are many studies on the association between high blood pressure and the risk of dementia or cognitive decline,312 and 2 clinical trials on blood pressure treatment and cognitive change.42,43 With few exceptions,13,29 the reported associations between high blood pressure and dementia have been restricted to levels greater than either 160 mm Hg for systolic pressure or 95 mm Hg for diastolic pressure. Participants in both clinical trials had blood pressures in this range, but only one trial44 found a reduced risk of dementia in the treated group. In our study, chronically high blood pressure (>160/90 mm Hg) during a 9-year period did not increase the risk of AD, nor was there evidence of an association with high pulse pressure. Few participants in the East Boston study had chronically high blood pressure levels, and there were few cases of vascular dementia (3 of 99 subjects with AD had evidence of vascular dementia).

The results of our study do not support the hypothesis that high blood pressure increases the risk of AD. The study could not address whether high blood pressure increases the risk of vascular dementia because there were few such cases in the East Boston population. Evidence suggests that cerebrovascular disease may alter the clinical expression of AD,44 and various associations observed between blood pressure and AD may be due to population differences in the prevalence of cerebrovascular disease. These relationships can be understood only by conducting longitudinal studies of large representative populations with a wide range of blood pressure levels and by using neuroimaging techniques for the diagnosis of cerebrovascular disease.

Accepted for publication July 18, 2001.

This study was supported by contract N01-AG-0-2107, grant AG05362, and cooperative agreement AG06789 from the National Institute on Aging, Bethesda, Md.

We thank the residents of East Boston and the staff of the East Boston Neighborhood Health Center for their cooperation and support.

Corresponding author and reprints: Martha Clare Morris, ScD, Rush Institute for Healthy Aging, Rush-Presbyterian-St Luke's Medical Center, 1645 W Jackson, Chicago, IL 60612 (e-mail: mmorris@rush.edu).

Skoog  I Vascular aspects in Alzheimer's disease. J Neural Transm Suppl.2000;59:37-43.
Sparks  DL Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer's disease? Ann N Y Acad Sci.1997;826:128-146.
Swan  GELaRue  ACarmelli  DReed  TEFabsitz  RR Decline in cognitive performance in aging twins: heritability and biobehavioral predictors from the National Heart, Lung, and Blood Institute Twin Study. Arch Neurol.1992;49:476-481.
Launer  LJMasaki  KPetrovitch  HFoley  DHavlik  RJ The association between midlife blood pressure levels and late-life cognitive function: the Honolulu-Asia Aging Study. JAMA.1995;274:1846-1851.
Elias  MFD'Agostino  RBElias  PKWolf  PA Neuropsychological test performance, cognitive functioning, blood pressure, and age: the Framingham Heart Study. Exp Aging Res.1995;21:369-391.
Kilander  LNyman  HBoberg  MHansson  LLithell  H Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. Hypertension.1998;31:780-786.
Glynn  RJBeckett  LAHebert  LEMorris  MCScherr  PAEvans  DA Current and remote blood pressure and cognitive decline. JAMA.1999;281:438-445.
Sacktor  NGray  SKawas  CHerbst  JCosta  PFleg  J Systolic blood pressure within an intermediate range may reduce memory loss in an elderly hypertensive cohort. J Geriatr Psychiatry Neurol.1999;12:1-6.
Haan  MNShemanski  LJagust  WJManolio  TAKuller  L The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA.1999;282:40-46.
Tzourio  CDufouil  CDucimetiere  PAlperovitch  A Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. Neurology.1999;53:1948-1952.
de Leeuw  FEde Groot  JCOudkerk  M  et al A follow-up study of blood pressure and cerebral white matter lesions. Ann Neurol.1999;46:827-833.
Carmelli  DSwan  GEReed  TWolf  PAMiller  BLDeCarli  C Midlife cardiovascular risk factors and brain morphology in identical older male twins. Neurology.1999;52:1119-1124.
DeCarli  CMiller  BLSwan  GE  et al Predictors of brain morphology for the men of the NHLBI Twin Study. Stroke.1999;30:529-536.
Swan  GEDeCarli  CMiller  BL  et al Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology.1998;51:986-993.
Strassburger  TLLu  HCDaly  EM  et al Interactive effects of age and hypertension on volumes of brain structures. Stroke.1997;28:1410-1417.
Amar  KLewis  TWilcock  GScott  MBucks  R The relationship between white matter low attenuation on brain CT and vascular risk factors: a memory clinic. Age Ageing.1995;24:411-415.
Shimada  KKawamoto  AMatsubayashi  KOzawa  T Silent cerebrovascular disease in the elderly: correlation with ambulatory pressure. Hypertension.1990;16:692-699.
Inzitari  DDiaz  FFox  A  et al Vascular risk factors and leuko-araiosis. Arch Neurol.1987;44:42-47.
Salerno  JAMurphy  DGMHorwitz  B  et al Brain atrophy in hypertension: a volumetric magnetic resonance imaging study. Hypertension.1992;20:340-348.
van Swieten  JCGeyskes  GGDerix  MMA  et al Hypertension in the elderly is associated with white matter lesions and cognitive decline. Ann Neurol.1991;30:825-830.
Steingart  AHachinski  VCLau  C  et al Cognitive and neurologic findings in demented patients with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis). Arch Neurol.1987;44:36-39.
Waldemar  GChristiansen  PLarsson  HB  et al White matter magnetic resonance hyperintensities in dementia of the Alzheimer type: morphological and regional cerebral blood flow correlates. J Neurol Neurosurg Psychiatry.1994;57:1458-1465.
Longstreth  WTManolio  TAArnold  A  et al Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people: the Cardiovascular Health Study. Stroke.1996;27:1274-1282.
DeCarli  CGrady  CLClark  CM  et al Comparison of positron emission tomography, cognition, and brain volume in AD with and without severe abnormalities of white matter. J Neurol Neurosurg Psychiatry.1996;60:158-167.
Breteler  MMBvan Swieten  JCBots  ML  et al Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology.1994;44:1246-1252.
de Groot  JCde Leeuw  FEOudkerk  M  et al Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol.2000;47:141-143.
Yoshitake  TKiyohara  YKato  I  et al Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. Neurology.1995;45:1161-1168.
Skoog  ILemfelt  BLandahl  S  et al 15-year longitudinal study of blood pressure and dementia. Lancet.1996;347:1141-1145.
Launer  LJRoss  GWPetrovitch  H  et al Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging.2000;21:49-55.
Cornoni-Huntley  JBrock  DBOstfeld  AMTaylor  JOWallace  RB Established Populations of Epidemiologic Studies of the Elderly Resource Data Book.  Washington, DC: Government Printing Offices; 1988.
Hebert  LEScherr  PABeckett  LA Age-specific incidence of Alzheimer's disease in a community population. JAMA.1995;273:1354-1359.
Albert  MSSmith  LAScherr  PATaylor  JOEvans  DAFunkenstein  HH The use of brief cognitive tests to identify individuals in the community with clinically diagnosed Alzheimer's disease. Int J Neurosci.1991;57:167-178.
Hypertension Detection and Follow-Up Program Cooperative Group Variability of blood pressure and the results of screening in the HDFP. J Chronic Dis.1978;31:651-657.
Glynn  RJField  TSSatterfield  S  et al Modification of increasing systolic blood pressure in the elderly during the 1980s. Am J Epidemiol.1993;138:365-379.
Curb  JDLabarthe  DRCooper  SPCutter  GRHawkins  CM Training and certification of blood pressure observers. Hypertension.1983;5:610-614.
McKhann  GDrachman  DFolstein  MKatzman  RPrice  DStadlan  EM Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology.1984;34:939-944.
Evans  DAFunkenstein  HAlbert  MS  et al Prevalence of Alzheimer's disease in a community population of older persons: higher than previously reported. JAMA.1989;262:2551-2556.
Rose  GABlackburn  HGillum  RFPrineas  RJ Cardiovascular Survey Methods.  Geneva, Switzerland: World Health Organization; 1982:162-165.
Hixson  JVernier  D Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhAIJ Lipid Res.1990;31:545-548.
Evans  DAHebert  LEBeckett  LA  et al Education and other measures of socioeconomic status and risk of incident Alzheimer disease in a defined population of older persons. Arch Neurol.1997;54:1399-1405.
Evans  DABeckett  LAField  TS  et al Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons. JAMA.1997;277:822-824.
Forette  FSeux  MLStaessen  JA  et al Prevention of dementia in randomized double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet.1998;352:1347-1351.
Gurland  BJTeresi  JSmith  WMBlack  DHughes  GEdlavitch  S Effects of treatment for isolated hypertension on cognitive status and depression in the elderly. J Am Geriatr Soc.1988;36:1015-1022.
Snowdon  DAGreiner  LHMortimer  JARiley  KPGreiner  PAMarkesbery  WR Brain infarction and the clinical expression of Alzheimer disease: the Nun Study. JAMA.1997;277:813-817.

Figures

Place holder to copy figure label and caption
Figure 1.

Sample design of the East Boston study (East Boston, Mass) of incident Alzheimer disease. EPESE indicates Established Populations for Epidemiologic Studies of the Elderly.

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Place holder to copy figure label and caption
Figure 2.

Mean blood pressure levels, adjusted for age and sex, from 13 years before clinical evaluation to 2 years after for persons affected (solid line) and unaffected (dotted line) with incident Alzheimer disease.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1 Blood Pressure Measurements Among 642 Persons Evaluated for Incident AD*
Table Graphic Jump LocationTable 2 Baseline Characteristics by Level of Baseline Blood Pressure of 634 Participants Who Were Clinically Evaluated for Incident Alzheimer Disease, East Boston, Mass, 1982-1985*
Table Graphic Jump LocationTable 3 Basic-Adjusted and Multiple-Adjusted ORs and 95% CIs for 4-Year Risk of Incident AD for Blood Pressure Measured Continuously (10–mm Hg Increments) and Categorically, East Boston Study (East Boston, Mass), 1982-1988*
Table Graphic Jump LocationTable 4 ORs and 95% CIs for 4-Year Risk of Incident AD by Antihypertensive Medication Use and Level of Systolic Pressure Based on Logistic Regression Models Adjusted for Age, Sex, and Level of Education, East Boston Study (East Boston, Mass), 1982-1988*
Table Graphic Jump LocationTable 5 ORs and 95% CIs of Incident AD by Level of Systolic and Diastolic Blood Pressure Measured 13 Years Earlier Among 378 Participants in the East Boston Study (East Boston, Mass), 1973-1988*

References

Skoog  I Vascular aspects in Alzheimer's disease. J Neural Transm Suppl.2000;59:37-43.
Sparks  DL Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer's disease? Ann N Y Acad Sci.1997;826:128-146.
Swan  GELaRue  ACarmelli  DReed  TEFabsitz  RR Decline in cognitive performance in aging twins: heritability and biobehavioral predictors from the National Heart, Lung, and Blood Institute Twin Study. Arch Neurol.1992;49:476-481.
Launer  LJMasaki  KPetrovitch  HFoley  DHavlik  RJ The association between midlife blood pressure levels and late-life cognitive function: the Honolulu-Asia Aging Study. JAMA.1995;274:1846-1851.
Elias  MFD'Agostino  RBElias  PKWolf  PA Neuropsychological test performance, cognitive functioning, blood pressure, and age: the Framingham Heart Study. Exp Aging Res.1995;21:369-391.
Kilander  LNyman  HBoberg  MHansson  LLithell  H Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. Hypertension.1998;31:780-786.
Glynn  RJBeckett  LAHebert  LEMorris  MCScherr  PAEvans  DA Current and remote blood pressure and cognitive decline. JAMA.1999;281:438-445.
Sacktor  NGray  SKawas  CHerbst  JCosta  PFleg  J Systolic blood pressure within an intermediate range may reduce memory loss in an elderly hypertensive cohort. J Geriatr Psychiatry Neurol.1999;12:1-6.
Haan  MNShemanski  LJagust  WJManolio  TAKuller  L The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA.1999;282:40-46.
Tzourio  CDufouil  CDucimetiere  PAlperovitch  A Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. Neurology.1999;53:1948-1952.
de Leeuw  FEde Groot  JCOudkerk  M  et al A follow-up study of blood pressure and cerebral white matter lesions. Ann Neurol.1999;46:827-833.
Carmelli  DSwan  GEReed  TWolf  PAMiller  BLDeCarli  C Midlife cardiovascular risk factors and brain morphology in identical older male twins. Neurology.1999;52:1119-1124.
DeCarli  CMiller  BLSwan  GE  et al Predictors of brain morphology for the men of the NHLBI Twin Study. Stroke.1999;30:529-536.
Swan  GEDeCarli  CMiller  BL  et al Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology.1998;51:986-993.
Strassburger  TLLu  HCDaly  EM  et al Interactive effects of age and hypertension on volumes of brain structures. Stroke.1997;28:1410-1417.
Amar  KLewis  TWilcock  GScott  MBucks  R The relationship between white matter low attenuation on brain CT and vascular risk factors: a memory clinic. Age Ageing.1995;24:411-415.
Shimada  KKawamoto  AMatsubayashi  KOzawa  T Silent cerebrovascular disease in the elderly: correlation with ambulatory pressure. Hypertension.1990;16:692-699.
Inzitari  DDiaz  FFox  A  et al Vascular risk factors and leuko-araiosis. Arch Neurol.1987;44:42-47.
Salerno  JAMurphy  DGMHorwitz  B  et al Brain atrophy in hypertension: a volumetric magnetic resonance imaging study. Hypertension.1992;20:340-348.
van Swieten  JCGeyskes  GGDerix  MMA  et al Hypertension in the elderly is associated with white matter lesions and cognitive decline. Ann Neurol.1991;30:825-830.
Steingart  AHachinski  VCLau  C  et al Cognitive and neurologic findings in demented patients with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis). Arch Neurol.1987;44:36-39.
Waldemar  GChristiansen  PLarsson  HB  et al White matter magnetic resonance hyperintensities in dementia of the Alzheimer type: morphological and regional cerebral blood flow correlates. J Neurol Neurosurg Psychiatry.1994;57:1458-1465.
Longstreth  WTManolio  TAArnold  A  et al Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people: the Cardiovascular Health Study. Stroke.1996;27:1274-1282.
DeCarli  CGrady  CLClark  CM  et al Comparison of positron emission tomography, cognition, and brain volume in AD with and without severe abnormalities of white matter. J Neurol Neurosurg Psychiatry.1996;60:158-167.
Breteler  MMBvan Swieten  JCBots  ML  et al Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology.1994;44:1246-1252.
de Groot  JCde Leeuw  FEOudkerk  M  et al Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol.2000;47:141-143.
Yoshitake  TKiyohara  YKato  I  et al Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. Neurology.1995;45:1161-1168.
Skoog  ILemfelt  BLandahl  S  et al 15-year longitudinal study of blood pressure and dementia. Lancet.1996;347:1141-1145.
Launer  LJRoss  GWPetrovitch  H  et al Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging.2000;21:49-55.
Cornoni-Huntley  JBrock  DBOstfeld  AMTaylor  JOWallace  RB Established Populations of Epidemiologic Studies of the Elderly Resource Data Book.  Washington, DC: Government Printing Offices; 1988.
Hebert  LEScherr  PABeckett  LA Age-specific incidence of Alzheimer's disease in a community population. JAMA.1995;273:1354-1359.
Albert  MSSmith  LAScherr  PATaylor  JOEvans  DAFunkenstein  HH The use of brief cognitive tests to identify individuals in the community with clinically diagnosed Alzheimer's disease. Int J Neurosci.1991;57:167-178.
Hypertension Detection and Follow-Up Program Cooperative Group Variability of blood pressure and the results of screening in the HDFP. J Chronic Dis.1978;31:651-657.
Glynn  RJField  TSSatterfield  S  et al Modification of increasing systolic blood pressure in the elderly during the 1980s. Am J Epidemiol.1993;138:365-379.
Curb  JDLabarthe  DRCooper  SPCutter  GRHawkins  CM Training and certification of blood pressure observers. Hypertension.1983;5:610-614.
McKhann  GDrachman  DFolstein  MKatzman  RPrice  DStadlan  EM Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology.1984;34:939-944.
Evans  DAFunkenstein  HAlbert  MS  et al Prevalence of Alzheimer's disease in a community population of older persons: higher than previously reported. JAMA.1989;262:2551-2556.
Rose  GABlackburn  HGillum  RFPrineas  RJ Cardiovascular Survey Methods.  Geneva, Switzerland: World Health Organization; 1982:162-165.
Hixson  JVernier  D Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhAIJ Lipid Res.1990;31:545-548.
Evans  DAHebert  LEBeckett  LA  et al Education and other measures of socioeconomic status and risk of incident Alzheimer disease in a defined population of older persons. Arch Neurol.1997;54:1399-1405.
Evans  DABeckett  LAField  TS  et al Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons. JAMA.1997;277:822-824.
Forette  FSeux  MLStaessen  JA  et al Prevention of dementia in randomized double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet.1998;352:1347-1351.
Gurland  BJTeresi  JSmith  WMBlack  DHughes  GEdlavitch  S Effects of treatment for isolated hypertension on cognitive status and depression in the elderly. J Am Geriatr Soc.1988;36:1015-1022.
Snowdon  DAGreiner  LHMortimer  JARiley  KPGreiner  PAMarkesbery  WR Brain infarction and the clinical expression of Alzheimer disease: the Nun Study. JAMA.1997;277:813-817.

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