Document Detail

Evaluation of the effect of systolic blood pressure and pulse pressure on cognitive function: the Women's Health and Aging Study II.
Jump to Full Text
MedLine Citation:
PMID:  22174760     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Evidence suggests that elevated systolic blood pressure (SBP) and pulse pressure (PP) in midlife is associated with increased risk for cognitive impairment later in life. There is mixed evidence regarding the effects of late life elevated SBP or PP on cognitive function, and limited information on the role of female gender.
METHODS/PRINCIPAL FINDINGS: Effects of SBPand PPon cognitive abilities at baseline and over a 9-year period were evaluated in 337 non-demented community-dwelling female participants over age 70 in the Women's Health and Aging Study II using logistic and Cox proportional hazards regression analyses. Participants aged 76-80 years with SBP≥160 mmHg or PP≥84 mmHg showed increased incidence of impairment on Trail Making Test-Part B (TMT, Part B), a measure of executive function, over time when compared to the control group that included participants with normal and pre-hypertensive SBP (<120 and 120-139 mmHg) or participants with low PP (<68 mmHg) (HR = 5.05 [95%CI = 1.42, 18.04], [HR = 5.12 [95%CI = 1.11; 23.62], respectively). Participants aged 70-75 years with PP≥71 mmHg had at least a two-fold higher incidence of impairment on HVLT-I, a measure of verbal learning, over time when compared to participants with low PP (<68 mmHg) (HR = 2.44 [95%CI = 1.11, 5.39]).
CONCLUSIONS/SIGNIFICANCE: Our data suggest that elevated SBP or PP in older non-demented women increases risk for late-life cognitive impairment and that PP could be used when assessing the risk for impairment in cognitive abilities. These results warrant further, larger studies to evaluate possible effects of elevated blood pressure in normal cognitive aging.
Authors:
Sevil Yasar; Jean Y Ko; Stephanie Nothelle; Michelle M Mielke; Michelle C Carlson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-09
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-12-16     Completed Date:  2012-04-23     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e27976     Citation Subset:  IM    
Affiliation:
Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America. syasar1@jhmi.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Aging / physiology*
Blood Pressure / physiology*
Cognition / physiology*
Cross-Sectional Studies
Demography
Female
Humans
Hypertension / physiopathology
Longitudinal Studies
Systole / physiology*
Women's Health*
Grant Support
ID/Acronym/Agency:
1F31AG030908-01-A1/AG/NIA NIH HHS; R01 AG11703-10/AG/NIA NIH HHS; R01 AG19825-02/AG/NIA NIH HHS
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): PLoS One
Journal ID (publisher-id): plos
Journal ID (pmc): plosone
ISSN: 1932-6203
Publisher: Public Library of Science, San Francisco, USA
Article Information
Download PDF
Yasar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received Day: 26 Month: 7 Year: 2011
Accepted Day: 28 Month: 10 Year: 2011
collection publication date: Year: 2011
Electronic publication date: Day: 9 Month: 12 Year: 2011
Volume: 6 Issue: 12
E-location ID: e27976
ID: 3235094
PubMed Id: 22174760
Publisher Id: PONE-D-11-14197
DOI: 10.1371/journal.pone.0027976

Evaluation of the Effect of Systolic Blood Pressure and Pulse Pressure on Cognitive Function: The Women's Health and Aging Study II Alternate Title:Systolic BP on Cognitive Function
Sevil Yasar12*
Jean Y. Ko3
Stephanie Nothelle4
Michelle M. Mielke25
Michelle C. Carlson23
James M. Wrightedit1 Role: Editor
1Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
2Center on Aging and Health, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
3Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
4Indiana University School of Medicine, Indianapolis, Indiana, United States of America
5Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, United States of America
University of British Columbia, Canada
Correspondence: * E-mail: syasar1@jhmi.edu
Contributed by footnote: Conceived and designed the experiments: SY JYK SN MMM MCC. Performed the experiments: SY JYK SN MMM MCC. Analyzed the data: SY JYK SN MMM MCC. Contributed reagents/materials/analysis tools: MCC. Wrote the paper: SY JYK SN MMM MCC.

Introduction

Hypertension (HTN), an elevation of systolic or diastolic or both systolic and diastolic blood pressures, is an important public health issue because of its high prevalence, approximately 26% in the general population [1], and because of associated high morbidity and mortality [2]. There is also evidence that age-related blood pressure changes occur and that these changes are gender-specific, namely systolic hypertension is more prevalent in elderly women than men [3]. These age-related blood pressure changes may account, in part, for the higher cardiovascular mortality reported among elderly females compared with elderly males [4][6], and should be considered an important target for preventive strategies in elderly females.

HTN has been extensively studied as a major risk factor for cognitive decline in older; community dwelling populations (see review [7]). While there is strong evidence that HTN in midlife is associated with increased risk for cognitive impairment later in life [8][13], there is mixed evidence regarding the effects of HTN in late life on cognitive function. One study reported no association [14], while other studies reported negative associations [15][18] between elevated baseline systolic blood pressure (SBP) and global cognitive function. Additionally, it is not clear whether specific cognitive abilities are more susceptible to the effects of elevated blood pressure in late life as one study showed a negative association between elevated SBP and learning and memory [19], another a negative association with attention, [20] and a third showed a negative association with naming and non-verbal memory [21]. There is currently no study available with a special focus on the role of SBP in late life and its effect on cognitive abilities in older women.

Pulse pressure (PP) is an independent predictor of all-cause and cardiovascular mortality [22]. High PP has been associated with Alzheimer's disease (AD) [23], poorer global cognitive function [24] and greater decline on verbal learning and non-verbal memory in individuals without dementia [25], when compared to participants with lower PP. However, there is currently no information available with a focus on the role of PP in late life and its effect on cognitive abilities in older women.

In the present study, we examined whether elevated SBP or PP in older women was associated with changes in cognitive abilities at baseline and over a 9-year period in a population of non-demented community-dwelling female participants, aged 70 to 80 years at baseline, in the Women's Health and Aging Study (WHAS) II.


Methods
Ethics Statement

This study was approved by the Johns Hopkins Institutional Review Board, and each participant gave informed, written consent before completing a standardized interview at each exam.

Data Source and Study Population

This study involved secondary data analysis using the WHAS II, a prospective study of physical functioning among the least disabled two thirds of 70- to 80-year-old, community dwelling women in eastern Baltimore, MD. Sampling and recruitment of this cohort is described in detail elsewhere [26] and complements WHAS I, a study of the one-third most disabled, community-dwelling older women. Trained interviewers determined eligibility at sampling according to whether individuals were (a) aged 70–79 years; (b) had sufficient hearing and proficiency in English to be interviewed; (c) could be contacted by telephone; (d) had a Mini-Mental State Exam (MMSE) [27] score >24; and (e) reported difficulty in no more than one of four functional domains: mobility and exercise tolerance, upper extremity strength, higher functioning (e.g., shopping), and basic self-care. Of 880 eligible individuals, 436 agreed to participate in the baseline examination. Those agreeing to participate were more highly educated and had more diseases than those who refused, but did not differ in other characteristics. Five follow-up exams were conducted at approximately 1.5-year intervals, with the exception of a 3-year interval between Exams 3 and 4, yielding a maximum of 9 years of follow-up. Each follow-up visit was conducted in the clinic or home, as needed and included standardized physical, cognitive and functional evaluations, and collection of demographic, psychosocial, medical and medication information. Over 9 years, 90 participants died and 103 participants were lost to follow-up.

Individuals who were missing blood pressure information at baseline were excluded (N = 2). Individuals who had scores under the impairment threshold (described below) were later excluded for longitudinal analyses (N = 98). The 336 remaining individuals represent 77.3% of the 436 participating individuals, and were included in both the cross-sectional and longitudinal analyses. The 100 individuals excluded from this study were comparable to those included in the study on age, systolic or diastolic blood pressure, and history of hypertension, but had lower MMSE scores (p<0.001), lower education (p<0.001), and were more likely to be black or other race (p<0.001).

Measures of Cognitive Function

Standardized cognitive testing by a trained technician was designed to comprehensively assess cognitive abilities in healthy older adults, and to be maximally sensitive to changes occurring with normal aging and to pathological changes occurring with dementia. Global cognitive status was assessed by the Mini-Mental State Exam (MMSE). The MMSE assesses five areas of cognitive function including orientation, attention, calculus, recall and language. The maximum score is 30 and a score of 24 or lower is suggestive of cognitive impairment. The Trail Making Test (TMT) [28], which is a pencil-and-paper test, was used to evaluate psychomotor speed via Part A and B, and executive function via Part B. Part A requires one to connect, as quickly as possible, a randomly distributed array of numbers sequentially from 1 to 25. Part B requires one to connect randomly distributed numbers and letters in an ascending alpha-numeric sequence. Participants were allotted a maximum time of 240 seconds on Part A and 360 seconds on Part B. Verbal immediate and delayed recall memory of 12 common objects were assessed using the Hopkins Verbal Learning Test-Revised (HVLT-R) [29]. Participants heard and recalled words during three successive learning trials (maximum = 36) and once after a 20-minute interval (maximum = 12).

Impairment on each of the cognitive assessments was defined as follows: Trail Making Part A (TMT-A) scores ≥81 seconds; Trail Making Part B (TMT-B) scores ≥225 seconds; Hopkins Verbal Learning Test immediate recall (HVLT-I) scores ≤16; Hopkins Verbal Learning Test delayed recall (HVLT-D) scores ≤4; MMSE scores ≤23 [30], [31]. These cut-points corresponded to approximately 1.5 to 1.8 standard deviations below internal norms at baseline on most tests.

Measures of Blood Pressure

At each study visit, blood pressure (BP) was measured by a trained nursing staff according to protocols. The participant's BP was measured while the participant was resting and sitting in an upright position with legs uncrossed and feet flat on the floor for approximately five minutes. Three blood pressure readings, with 30-second intervals between each measurement, were obtained on the right arm using a mercury sphygmomanometer with an appropriate-sized occluding cuff and were averaged for data analysis.

Systolic hypertension status was stratified according to SBP readings as control group (SBP≤139 mmHg), HTN I group (SBP = 140–159 mmHg) and HTN II group (SBP≥160 mmHg) PP, was defined as the difference between SBP and DBP, and participants were assigned to the lower (PP = 48–68 mmHg), middle (PP = 71–77 mmHg) and upper (PP = 84–108 mmHg) tertile group according to their PP, where the lower tertile group served as the control group.

Statistical Analyses

STATA 10.2 was used for all analyses (StataCorp, College Station, TX). We compared baseline demographic and health characteristics by HTN stage and PP tertile using chi-square tests for categorical variables and ANOVA with pair wise comparisons for continuous variables. In order to assess the baseline prevalence of impairment in cognitive abilities first cross-sectional analysis, using logistic regression models, were conducted. In order to assess the long-term effect of SBP and PP on the risk of developing impairment in each cognitive ability over the 9-year follow-up period, longitudinal, multivariate discrete-time Cox proportional hazard models [32] were conducted. The discrete-time Cox models have advantages over traditional, continuous proportional-Cox models in that the event, such as last visit or death, can occur over a discrete time; use of this model is especially appealing in analyzing longitudinal data with regularly scheduled visits. The model compares each case of newly diagnosed impairment with all other subjects in the study who were free of impairment at that visit when the impairment was diagnosed. Subjects contributed information up to the visit when the diagnosis of impairment occurred, or up to their last study visit.

Analyses, in Model 1 were first adjusted for the well known confounding effects of age [33], race (white vs. non-white) [34] and education (<12,  = 12, >12 years of education) [35]. Then, in Model 2, in addition to age, race, and education they were adjusted for income (<$10,000/yr, $10,000–24,999/yr, $25,000–49,999, >$50,000/yr), smoking status (never vs. ever), comorbidities such as history of HTN, stroke, myocardial infarction (MI) or angina, congestive heart failure (CHF), peripheral artery disease (PAD), diabetes mellitus (DM); depression (measured by Geriatric Depression Scale [36]), Body Mass Index (BMI, Body Mass Index (kg/m2), serum glucose level (mg/dl), total cholesterol level (mg/dl), and history of ever taking antihypertensive medications. The a priori p-value was set at p<0.05.

First, we evaluated the effect of SBP and PP on cognitive abilities in all participants, then, in separate analyses, we stratified subjects according to their age, 70–75 years old or 76–80 years old, to evaluate the possible role of age.


Results
Participants

The average age of the 336 participants at baseline was 74.1 years (ranging from 70–80 years), 41% had a college education and 81% were white (Table 1). 51% reported history of HTN and 52% reported antihypertensive medication use (Table 1). The prevalence of stroke, MI, angina, CHF, PAD, and DM, was 3.6%, 8.9%, 14.9%, 7.6%, 9.6% and 9.4%, respectively. The baseline means for MMSE, TMT Part A and Part B times (sec), and HVLT-I and -D scores were indicative of a high functioning sample (Table 2).

The participants in the HTN II group had higher prevalence of an HTN history and reported antihypertensive medication use, and higher SBP, DBP and PP, compared to the control group. The participants in the upper tertile PP group were more often white, had lower education levels, had a higher prevalence of HTN history, MI history, CHF history, reported antihypertensive medication use, and higher SBP, DBP and PP compared to the control group (Table 1).

SBP and Cognitive Function

In the cross sectional analyses, participants with HTN I had lower odds of impairment on the TMT, Part A (HR = 0.29 [95%CI = 0.09, 0.96]) compared to the control group. There were no differences in HTN I and II groups, and the control group in odds of impairment on the MMSE, TMT Part B, HVLT-I, HVLT-D after full adjustment in Model 2 (Table 3).

In the longitudinal analyses risk of cognitive impairment on any test did not differ by SBP levels (Table 4). However, when participants were stratified according to their age, participants aged between 76 and 80 years in the HTN II group had a five-fold greater increased risk of impairment on TMT-B compared to the control group (HR = 5.05 [95%CI = 1.42, 18.04]). There were no associations between SBP levels and risk of cognitive impairment among those aged 70–75 (Table 5).

PP and Cognitive Function

In cross sectional analyses odds of impairment on any cognitive test did not differ by PP tertile (Table 3).

In the longitudinal analyses, participants in the upper versus lower tertile, had a greater risk of impairment in executive function assessed by TMT, Part B (HR = 2.14 [95%CI = 1.29, 3.57]) compared to the lower tertile. Notably, this association was largely driven by the women aged 76–80 years old in the highest PP tertile who had a five-fold greater risk of TMT, Part B impairment compared to the lower tertile (HR = 5.12 [95%CI = 1.11; 23.62]) (Table 3 and 4). However, participants aged between 70–75 years in both the middle and upper tertile group had a greater risk of verbal learning impairment assessed by HVLT-I (HR = 2.44, 95% CI [1.11, 5.39]; HR = 3.13) [95%CI = 1.35, 7.24], respectively (Table 4) when compared to the control group.


Discussion

In this study we evaluated effects of elevated SBP or PP on cognitive abilities, such as global cognitive function, speed of processing, executive function, visuospatial function, and verbal learning and memory, at baseline and over a 9-year period in non-demented older community-dwelling female participants, in the WHAS II. Our results showed that women aged between 76–80 years with SBP≥160 mmHg or with PP≥84 mmHg showed five times higher incidence of impairment on TMT, Part B, a measure of executive function, when compared to their control groups. We also found that participants aged 70–75 years at baseline with PP≥84 mmHg had two- to three-fold higher incidence of impairment in HVLT-I, a measure of verbal learning. Our data suggest that elevated SBP and PP in older non-demented women increases the risk for cognitive impairment in late-life.

With increasing life expectancy the number of older people, especially older women who have a higher prevalence of HTN [3], including elevated SBP and/or DBP, also increases. HTN in midlife has been shown to be risk factor for lower cognitive function in later life [7], but there is mixed evidence for an effect of HTN in late-life on cognitive function, with information mostly limited to measures of global cognitive function [14][18], [37]. There are few studies, with none looking specifically at older women, reporting associations between elevated SBP and impairment in specific cognitive abilities in late life [13], [20], [21], and findings from these studies indicate that the affected cognitive abilities are dependent on the participants' age and the length of follow-up [19][21]. Our results extend these findings to older women, aged between 76–80 years, by showing detrimental effects of elevated SBP≥160 mmHg and PP≥84 mmHg in late life on executive function, in the absence of dementia, over a 9-year period. Our study also suggests that PP is maybe a more sensitive measure for cognitive decline, since it takes into account both the effects of SBP and DBP.

Several mechanisms have been proposed and evaluated to explain associations between elevated blood pressure and specific cognitive abilities. It has been suggested that chronic HTN, by hastening the atherosclerotic process in deep white matter vessels, has a detrimental effect on sub-cortical white matter circuits [7], which may account for impairment in specific cognitive abilities such as executive function [38]. This seems to be confirmed by imaging studies using magnetic resonance imaging (MRI) of individuals with HTN which have found an increased number of white matter abnormalities in the frontal lobe [39]. Our current findings are in line with these studies, namely we found an association between elevated SBP and impairment on TMT, Part B, a measure of executive function.

There is a long standing hypothesis that HTN-associated changes in the brain may interact with age-associated changes. Thus the measured effect will be larger in older than in younger hypertensive people [40] and this effect could be captured better by measures of arterial stiffness such as PP rather than SBP. Our study partially supports this hypothesis by showing the detrimental effect of elevated SBP and also PP only in women aged 76–80, but not those aged 70–75. However, verbal learning was found to be worse in the younger group with the highest PP and this effect was not seen in the older group and also not seen when evaluating the effect of SBP. This could be partially explained by the different brain areas involved in the different tasks, i.e. executive function versus verbal learning, and their sensitivity to hypertension- and age-associated changes.

There are some limitations of this study. First, the sample size was relatively small and was composed of women, which may limit generalization of these findings to the whole population. Second, as is true in all observational studies, our results may be vulnerable to confounding. It is possible that HTN and risk of cognitive decline reflect the association of antihypertensive medication use with yet another unmeasured variable. Third, we conducted numerous comparisons, which could raise the possibility of our significant findings being there by chance. Fourth, information on mild cognitive impairment or dementia diagnosis is not currently available, but adjudication is ongoing. Fifth, as in all studies with aging cohorts, survival bias may be an issue, since people with HTN might be more likely to die due to the increased mortality risk associated with HTN. Last, there is selective loss to follow-up of those most impaired, as found in most population-based studies, but this would lead to underestimation of true rates of decline and a more conservative estimate of our findings.

There are a number of advantages of this study. First, is its population-based study which examined only female participants initially free of cognitive and functional impairment and followed them up to 9 years. Second, there were frequent and repeated comprehensive cognitive assessments. Third, we were able to take into consideration the effects of antihypertensive medications and their effects on the brain and cognitive function by adjusting for antihypertensive medication use.

Moderately elevated SBP levels have been considered acceptable in older patients due to fear of hypoperfusion. However, clinical trials, and most recently the Hypertension in the very Elderly (HYVET) clinical trial [41], have shown that reducing blood pressures in people older than 80 years from 173/91 to at least 150/80 mmHg in 48% of the people in the active treatment group resulted in decreased death from stroke and death from any-cause. Although, it needs to be noted that the HYVET-Cog study showed no benefits in terms of prevention of dementia or incidence of global cognitive decline [42], which may have been due to either the short follow-up secondary to the early termination of the trial, or to the lack of treatment effect. Although our study was an observational study, our results could provide additional argument that treating elevated SBP≥160 mmHg in the older population, especially women, could not only result in decreased mortality, but also in the preservation of cognitive function, specifically executive function.

Our data suggests that elevated SBP or PP in older non-demented women increases risk for late-life cognitive impairment. These results warrant further, larger studies to evaluate possible effects of elevated blood pressure in normal cognitive aging.


Notes

Competing Interests: The authors have declared that no competing interests exist.

Funding: This study was supported in part by NIH grants RO1 AG19825-02 and RO1 AG11703-10 from the National Institute on Aging, National Institutes of Health. Jean Y. Ko was supported by the National Institute of Aging (NIA: 1F31AG030908-01-A1) and Stephanie Nothelle was supported by the 2008 Medical Student Training in Aging Research (MSTAR) Program by The American Federation for Aging Research (AFAR) and the National Institute on Aging (NIA). The funders had no role in the study design, data collection, and analysis, decision to publish or preparation of the manuscript.

Portions of this study were presented at the Annual Scientific Meeting of the American Geriatrics Society, April 29–May 2, 2009, Chicago, IL.


References
1. Kearney PM,Whelton M,Reynolds K,Whelton PK,He J. Year: 2004Worldwide prevalence of hypertension: A systematic review.J Hypertens22111915106785
2. Ezzati M,Lopez AD,Rodgers A,Vander Hoorn S,Murray CJ. Year: 2002Comparative Risk Assessment Collaborating Group. Selected major risk factors and global and regional burden of disease.Lancet3601347136012423980
3. Martins D,Nelson K,Pan D,Tareen N,Norris K. Year: 2001The effect of gender on age-related blood pressure changes and the prevalence of isolated systolic hypertension among older adults: Data from NHANES III.J Gend Specif Med4103, 2011605350
4. Abbott RD,Donahue RP,Kannel WB,Wilson PW. Year: 1988The impact of diabetes on survival following myocardial infarction in men vs women. The Framingham Study.JAMA260345634602974889
5. Legato MJ. Year: 1998Cardiovascular disease in women: Gender-specific aspects of hypertension and the consequences of treatment.J Womens Health71992099555685
6. Kannel WB,Wilson PW,D'Agostino RB,Cobb J. Year: 1998Sudden coronary death in women.Am Heart J1362052129704680
7. Birns J,Kalra L. Year: 2009Cognitive function and hypertension.J Hum Hypertens23869618650838
8. Elias MF,Wolf PA,D'Agostino RB,Cobb J,White LR. Year: 1993Untreated blood pressure level is inversely related to cognitive functioning: The Framingham Study.Am J Epidemiol1383533648213741
9. Launer LJ,Masaki K,Petrovitch H,Foley D,Havlik RJ. Year: 1995The association between midlife blood pressure levels and late-life cognitive function. The Honolulu-Asia Aging Study.JAMA274184618517500533
10. Swan GE,DeCarli C,Miller BL,Reed T,Wolf PA,et al. Year: 1998Association of midlife blood pressure to late-life cognitive decline and brain morphology.Neurology519869939781518
11. Kilander L,Nyman H,Boberg M,Lithell H. Year: 2000The association between low diastolic blood pressure in middle age and cognitive function in old age. A population-based study.Age Ageing2924324810855907
12. Kivipelto M,Helkala EL,Hanninen T,Laakso MP,Hallikainen M,et al. Year: 2001Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study.Neurology561683168911425934
13. Elias PK,Elias MF,Robbins MA,Budge MM. Year: 2004Blood pressure-related cognitive decline: Does age make a difference?Hypertension4463163615466661
14. Hebert LE,Scherr PA,Bennett DA,Bienias JL,Wilson RS,et al. Year: 2004Blood pressure and late-life cognitive function change: A biracial longitudinal population study.Neurology622021202415184608
15. Guo Z,Fratiglioni L,Winblad B,Viitanen M. Year: 1997Blood pressure and performance on the mini-mental state examination in the very old. cross-sectional and longitudinal data from the kungsholmen project.Am J Epidemiol145110611139199540
16. Tzourio C,Dufouil C,Ducimetiere P,Alperovitch A. Year: 1999Cognitive decline in individuals with high blood pressure: A longitudinal study in the elderly. EVA study group. Epidemiology of vascular aging.Neurology531948195210599763
17. Glynn RJ,Beckett LA,Hebert LE,Morris MC,Scherr PA,et al. Year: 1999Current and remote blood pressure and cognitive decline.JAMA2814384459952204
18. Piguet O,Grayson DA,Creasey H,Bennett HP,Brooks WS,et al. Year: 2003Vascular risk factors, cognition and dementia incidence over 6 years in the sydney older persons study.Neuroepidemiology2216517112711848
19. Elias MF,Elias PK,Sullivan LM,Wolf PA,D'Agostino RB. Year: 2003Lower cognitive function in the presence of obesity and hypertension: The Framingham Heart Study.Int J Obes Relat Metab Disord2726026812587008
20. Knopman D,Boland LL,Mosley T,Howard G,Liao D,et al. Year: 2001Cardiovascular risk factors and cognitive decline in middle-aged adults.Neurology56424811148234
21. Waldstein SR,Giggey PP,Thayer JF,Zonderman AB. Year: 2005Nonlinear relations of blood pressure to cognitive function: The Baltimore Longitudinal study of aging.Hypertension4537437915699446
22. de Simone G,Roman MJ,Alderman MH,Galderisi M,de Divitiis O,et al. Year: 2005Is high pulse pressure a marker of preclinical cardiovascular disease?Hypertension4557557915767471
23. Qiu C,Winblad B,Viitanen M,Fratiglioni L. Year: 2003Pulse pressure and risk of Alzheimer disease in persons aged 75 years and older: A community-based, longitudinal study.Stroke3459459912624277
24. Obisesan TO,Obisesan OA,Martins S,Alamgir L,Bond V,et al. Year: 2008High blood pressure, hypertension, and high pulse pressure are associated with poorer cognitive function in persons aged 60 and older: The third National Health and Nutrition Examination Survey.J Am Geriatr Soc5650150918179496
25. Waldstein SR,Rice SC,Thayer JF,Najjar SS,Scuteri A,et al. Year: 2008Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging.Hypertension519910418025297
26. Fried LP,Bandeen-Roche K,Kasper JD,Guralnik JM. Year: 1999Association of comorbidity with disability in older women: The Women's Health and Aging Study.J Clin Epidemiol5227379973071
27. Folstein MF,Folstein SE,McHugh PR. Year: 1975“Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician.J Psychiatr Res121891981202204
28. Reitan RM. Year: 1958Validity of the trail making test as an indicator of organic brain damage.Perceptual and Motor Skills8271276
29. Brandt J. Year: 1991The Hopkins Verbal Learning Test: Development of a new memory test with six equivalent forms.Clin Neuropsychol5125142
30. Benedict RH,Schretlen D,Groninger L,Brandt J. Year: 1998Hopkins Verbal Learning Test - Revised: Normative data and analysis of inter-form and test-retest reliability.Clin Neuropsychol124355
31. Ivnik RJ,Malec JF,Smith GE,Tangalos EG,Petersen RC. Year: 1996Neuropsychological tests' norms above age 55: COWAT, BNT, MAE token, WRAT-R reading, AMNART, STROOP, TMT, and JLO.Clin Neuropsychol10262278
32. Prentice RL,Gloeckler LA. Year: 1978Regression analysis of grouped survival data with application to breast cancer data.Biometrics345767630037
33. Brookmeyer R,Evans DA,Herbert L,Langa KM,Heeringa SG,et al. Year: 2011National estimates of the prevalence of Alzheimer's disease in the United States.Alzheimers Dement7617321255744
34. Froelich TE,Bogardus ST Jr,Inouye SK. Year: 2001Dementia and race: are there differences between African Americans and Caucasians?J Am Geriatr Soc494778411347796
35. Sharp ES,Gatz M. Year: 2011Relationship between education and dementia: An updated systematic review.Alzheimer Dis Assoc Disord In press.
36. Yesavage JA,Brink TL,Rose TL,Lum O,Huang V,et al. Year: 1982Development and validation of a geriatric depression screening scale: A preliminary report.J Psychiatr Res1737497183759
37. Bohannon AD,Fillenbaum GG,Pieper CF,Hanlon JT,Blazer DG. Year: 2002Relationship of race/ethnicity and blood pressure to change in cognitive function.J Am Geriatr Soc5042442911943035
38. Cummings JL. Year: 1993Frontal-subcortical circuits and human behavior.Arch Neurol508738808352676
39. Kuller LH,Margolis KL,Gaussoin SA,Bryan NR,Kerwin D,et al. Year: 2010Relationship of hypertension, blood pressure, and blood pressure control with white matter abnormalities in the Women's Health Initiative Memory Study (WHIMS)-MRI trial.J Clin Hypertens12203212
40. Wilkie F,Eisdorfer C. Year: 1971Intelligence and blood pressure in the aged.Science1729599625573571
41. Beckett NS,Peters R,Fletcher AE,Staessen JA,Liu L,et al. Year: 2008Treatment of hypertension in patients 80 years of age or older.N Engl J Med3581887189818378519
42. Peters R,Beckett N,Forette F,Tuomilehto J,Clarke R,et al. Year: 2008Incident dementia and blood pressure lowering in the hypertension in the very elderly trial cognitive function assessment (HYVET-COG): A double-blind, placebo controlled trial.Lancet Neurol768368918614402

Tables
[TableWrap ID: pone-0027976-t001] doi: 10.1371/journal.pone.0027976.t001.
Table 1  Baseline Sociodemographic Characteristics of Participants by Hypertension Status and Pulse Pressure, WHAS II (N = 336).
Characteristics PP PP PP Statistics
Control Group HTN I HTN II Statistics Lower Tertile Middle Tertile Upper Tertile
(N = 103) (N = 124) (N = 109) p (N = 117) (N = 107) (N = 112) p
N (%) N (%)
Age (Mean, SD) 73.5 (2.9) 73.7 (2.8) 74.1 (2.7) 0.2 73.4 (2.7) 73.9 (2.9) 74.02 (2.7) 0.2
Race:
White 87 (84.5) 101 (81.5) 97 (89.0) 0.3 90 (76.9) 95 (88.8) 99 (88.4) 0.02
Education:
<12 years 9 (8.7) 11 (8.9) 7 (6.4) 0.5 12 (10.3) 12 (11.2) 3 (2.7) 0.01
 = 12 years 43 (41.7) 61 (49.2) 57 (52.3) 48 (41.0) 45 (42.1) 68 (60.7)
>12 years 51 (49.5) 52 (41.9) 45 (41.3) 57 (48.7) 50 (46.7) 41 (36.6)
Income ($/year):
<10,000 20 (24.4) 25 (24.5) 21 (23.1) 0.5 24 (24.5) 24 (27.9) 18 (20.0) 0.6
10,000–24,999 27 (32.9) 32 (31.4) 38 (41.8) 33 (33.7) 26 (30.2) 38 (42.2)
25,000–49,999 19 (23.2) 23 (22.6) 22 (24.2) 26 (26.5) 20 (23.3) 18 (20.0)
>50,000 16 (19.5) 22 (21.6) 10 (11.0) 15 (15.3) 16 (18.6) 16 (17.8)
Marital status:
Married 64 (62.1) 70 (56.5) 70 (64.2) 0.4 77 (65.8) 60 (56.1) 68 (60.7) 0.3
Not Married 39 (37.9) 54 (43.6) 39 (35.8) 40 (34.2) 47 (43.9) 44 (39.3)
Smoking:
Never 57 (55.3) 67 (54.0) 57 (52.8) 0.91 65 (55.6) 59 (55.1) 58 (52.3) 0.9
Ever 46 (44.7) 57 (46.0) 51 (47.2) 52 (44.4) 48 (44.9) 53 (47.8)
Hx HTN 29 (27.9) 68 (54.8) 75 (68.8) <0.001 51 (43.6) 52 (48.6) 69 (61.6) 0.02
Hx Stroke 4 (3.9) 4 (3.2) 4 (3.7) 0.7 5 (4.3) 4 (3.7) 3 (2.7) 0.5
Hx MI 6 (5.8.2) 11 (8.9) 11(10.1) 0.5 5 (4.3) 7 (6.5) 16 (14.3) 0.02
Hx Angina 19 (8.3) 18 (14.5) 14 (12.8) 0.5 16 (13.7) 19 (17.6) 16 (14.3) 0.7
Hx CHF 6 (5.8) 8 (6.5) 9 (8.3) 0.8 10 (8.6) 2 (1.9) 11 (9.8) 0.04
Hx PAD 10 (9.6) 9 (7.3) 12 (11.0) 0.6 12 (10.3) 6 (5.6) 13 (11.6) 0.3
Hx DM 8 (7.7) 12 (9.7) 6 (5.5) 0.5 11 (9.4) 7 (6.5) 8 (7.1) 0.7
Ever taking HTN medications
54 (51.9) 101 (81.5) 92 (84.4) <0.001 77 (65.8) 79 (73.8) 90 (80.4) 0.04
Mean (SD) Mean (SD)
SBP (mmHg) 129.1 (9.1) 148.9 (5.0) 177.6 (12.0) <0.001 138.1 (18.4) 150.6 (17.1) 167.9 (17.1) <0.001
DBP (mmHg) 67.4 (10.1) 73.4 (11.8) 88.2 (17.0) <0.001 80.0 (15.9) 76.6 (16.8) 72.1 (13.5) <0.001
PP (mmHg) 61.7 (12.6) 75.5 (12.7) 89.5 (17.7) <0.001 58.1 (10.0) 73.9 (3.4) 95.8 (12.0) <0.001
BMI 25.9 (5.7) 27.3 (5.0) 26.5 (4.6) 0.1 26.7 (5.4) 26.2 (4.5) 27.0 (5.4) 0.5
GDS 3.7 (3.6) 3.9 (4.1) 3.5 (2.9) 0.7 3.4 (3.3) 4.2 (4.0) 3.7 (3.5) 0.3
Mean years to follow up
6.4 (8.7) 7.0 (6.0) 6.6 (6.2) 0.8 6.4 (8.2) 7.4 (4.9) 6.3 (7.3) 0.4

Control group (SBP≤139 mmHg); HTN I = Hypertension I (SBP 140–159 mmHg); HTN II = Hypertension II (SBP≥160); PP lower tertile = Pulse pressure 48–68 mmHg, PP middle tertile = Pulse pressure 71–77 mmHg, and PP upper tertile = Pulse pressure 84–108 mmHg.

Statistics = Chi-square test was used for categorical and ANOVA with pairwise comparisons for continuous variables.

Hx HTN = history of high blood pressure, Hx stroke = history of stroke, Hx MI = history of myocardial infarction, Hx Angina = history of angina, Hx CHF = history of congestive heart failure, Hx PAD = history of peripheral artery disease, Hx DM = history of diabetes mellitus; BMI = Body Mass Index, GDS = Geriatric Depression Scale.


[TableWrap ID: pone-0027976-t002] doi: 10.1371/journal.pone.0027976.t002.
Table 2  Means (SD) of Performances of Global and Domain Specific Cognitive Function for Exam 1–6 (9-year interval).
Exam 1 Exam 2 Exam 3 Exam 4 Exam 5 Exam 6
Mean (SD)
MMSE 28.6 (1.4) 28.4 (1.8) 27.9 (2.1) 28.1 (2.5) 27.9 (2.4) 27.4 (3.0)
TMT, Part A 40.3 (12.2) 45.0 (22.0) 47.1 (24.9) 52.1 (29.1) 53.1 (33.5) 55.5 (30.6)
TMT, Part B 104.1 (35.7) 119.1 (61.1) 140.0 (80.7) 161.1 (95.2) 174.7 (104.3) 179.8 (103.2)
HVLT-I 24.2 (4.1) 23.5 (4.7) 24.3 (5.2) 22.4 (5.6) 21.8 (5.5) 22.7 (6.4)
HVLT- D 9.1 (1.9) 8.6 (2.4) 8.7 (2.5) 7.8 (2.9) 7.7 (3.1) 7.5 (3.4)

MMSE = Mini Mental State Exam; TMT, Part A = Trail Making Test, Part A; TMT, Part B = Trail Making Test, Part B; HVLT = Hopkins Verbal Learning Test (HVLT-I = immediate recall; HVLT-D = delayed recall).


[TableWrap ID: pone-0027976-t003] doi: 10.1371/journal.pone.0027976.t003.
Table 3  Cross-Sectional Analysis of Hypertension Stages and Pulse Pressure Tertiles on Cognitive Function at Baseline.
HTN I HTN II PP Middle Tertile PP Upper Tertile
HR (95%CI) HR (95%CI) HR(95%CI) HR (95%CI)
HVLT-D
Unadjusted 0.75(0.32,1.76) 0.92(0.40,2.12) 0.74(0.31,1.76) 0.94(0.42,2.10)
Model 1 0.75(0.31,1.80) 1.08(0.45,2.58) 0.80(0.32,1.96) 1.19(0.51,2.77)
Model 2 0.75(0.28,1.99) 1.37(0.51,3.70) 0.71(0.27,1.87) 1.44(0.56,3.67)
HVLT-I
Unadjusted 0.96(0.44,2.10) 1.24(0.58,2.65) 0.65(0.30,1.42) 0.85(0.41,1.75)
Model 1 0.96(0.42,2.16) 1.41(0.63,3.15) 0.65(0.29,1.48) 1.00(0.47,2.14)
Model 2 0.77(0.30,1.97) 1.59(0.62,4.07) 0.52(0.21,1.28) 0.98(0.42,2.31)
TMT, Part A
Unadjusted 0.45(0.18,1.11) 0.43(0.17,1.11) 0.37(0.13,1.04) 0.56(0.23,1.37)
Model 1 0.35(0.12,0.98)* 0.59(0.21,1.67) 0.44(0.14,1.38) 0.92(0.33,2.53)
Model 2 0.29(0.09,0.96)* 0.49(0.13,1.79) 0.36(0.09,1.38) 0.95(0.30,2.98)
TMT, Part B
Unadjusted 1.42(0.60,3.39) 1.65(0.69,3.95) 0.74(0.31,1.80) 1.28(0.59,2.79)
Model 1 1.07(0.43,2.72) 1.56(0.62,3.90) 0.65(0.25,1.67) 1.36(0.60,3.12)
Model 2 1.26(0.42,3.73) 2.12(0.71,6.35) 0.75(0.26,2.16) 2.09(0.82,5.35)
MMSE
Unadjusted 0.20(0.02,1.85) 0.69(0.15,3.12) 0.23(0.03,1.98) 0.43(0.08,2.26)
Model 1 0.15(0.01,1.45) 0.80(0.16,4.06) 0.24(0.03,2.16) 0.45(0.08,2.48)
Model 2 0.08(0.01,1.05) 0.24(0.03,2.09) 0.18(0.01,2.32) 0.25(0.03,2.29)

Reference group for HTN: control group (SBP≤139 mmHg); for PP: pulse pressure lower tertile (48–68 mmHg).

HTN I = Hypertension I (SBP 140–159 mmHg); HTN II = Hypertension II (SBP≥160); PP middle tertile = Pulse pressure 71–77 mmHg, and PP upper tertile = Pulse pressure 84–108 mmHg.

Model 1: age, race, education.

Model 2: age, race, education, history of high blood pressure, stroke, myocardial infarction, congestive heart failure, peripheral artery disease, diabetes mellitus, angina; history of smoking, BMI, ever on hypertensive medication, glucose, cholesterol, and depression score.

Note: All Trails B models adjust for Trails A performance.

MMSE = Mini Mental State Exam; TMT, Part A = Trail Making Test, Part A; TMT, Part B = Trail Making Test, Part B; HVLT = Hopkins Verbal Learning Test (HVLT-I = immediate recall; HVLT-D = delayed recall);

*p-value<0.05.

** p-value<0.01.


[TableWrap ID: pone-0027976-t004] doi: 10.1371/journal.pone.0027976.t004.
Table 4  Longitudinal Analysis of Hypertension Stages and Pulse Pressure Tertiles on Cognitive Decline.
HTN I HTN II PP Middle Tertile PP Upper Tertile
HR (95% CI) HR (95% CI) HR (95% CI) HR (95% CI)
HVLT-D
Unadjusted 1.18 (0.70–2.00) 1.02 (0.58–1.78) 0.97 (0.57–1.65) 1.06 (0.63–1.80)
Model 1 1.06 (0.62–1.81) 0.96 (0.54–1.68) 0.97 (0.56–1.66) 1.13 (0.65–1.96)
Model 2 1.23 (0.67–2.27) 1.16 (0.60–2.23) 0.88 (0.50–1.55) 1.24 (0.69–2.22)
HVLT-I
Unadjusted 1.12 (0.67–1.87) 1.05 (0.61–1.80) 1.56 (0.92–2.62) 1.27 (0.74–2.18)
Model 1 1.08 (0.64–1.81) 1.03 (0.59–1.78) 1.74 (1.01–2.99)* 1.45 (0.82–2.58)
Model 2 1.35 (0.75–2.41) 1.37 (0.73–2.55) 1.53 (0.88–2.68) 1.58 (0.87–2.90)
TMT, Part A
Unadjusted 1.49 (0.81–2.75) 1.34 (0.70–2.56) 0.87 (0.47–1.61) 1.11 (0.62–1.98)
Model 1 1.34 (0.71–2.50) 1.43 (0.74–2.75) 1.04 (0.55–1.95) 1.59 (0.85–2.97)
Model 2 1.44 (0.69–2.99) 1.60 (0.75–3.45) 0.93 (0.46–1.89) 1.49 (0.75–2.93)
TMT, Part B
Unadjusted 1.12 (0.67–1.88) 1.20 (0.72–2.01) 0.88 (0.55–1.43) 1.46 (0.95–2.26)
Model 1 1.03 (0.61–1.73) 1.15 (0.68–1.93) 1.02 (0.62–1.69) 1.88 (1.16–3.02)
Model 2 0.90 (0.49–1.65) 1.27 (0.70–2.32) 0.98 (0.58–1.64) 2.14 (1.29–3.57)**
MMSE
Unadjusted 0.90 (0.42–1.91) 1.82 (0.92–3.60) 0.96 (0.48–1.95) 1.28 (0.66–2.48)
Model 1 0.80 (0.37–1.71) 1.84 (0.92–3.67) 1.15 (0.56–2.36) 1.54 (0.75–3.13)
Model 2 0.83 (0.36–1.97) 1.93 (0.86–4.36) 1.11 (0.53–2.35) 1.27 (0.59–2.74)

Reference group for HTN: control group (SBP≤139 mmHg); for PP: pulse pressure lower tertile (48–68 mmHg).

HTN I = Hypertension I (SBP 140–159 mmHg); HTN II = Hypertension II (SBP≥160); PP middle tertile = Pulse pressure 71–77 mmHg, and PP upper tertile = Pulse pressure 84–108 mmHg.

Model 1: age, race, education.

Model 2: age, race, education, history of high blood pressure, stroke, myocardial infarction, congestive heart failure, peripheral artery disease, diabetes mellitus, angina; history of smoking, BMI, ever on hypertensive medication, glucose, cholesterol, and depression score.

Note: All Trails B models adjust for Trails A performance.

MMSE = Mini Mental State Exam; TMT, Part A = Trail Making Test, Part A; TMT, Part B = Trail Making Test, Part B; HVLT = Hopkins Verbal Learning Test (HVLT-I = immediate recall; HVLT-D = delayed recall);

*p-value<0.05.

**p-value<0.01.


[TableWrap ID: pone-0027976-t005] doi: 10.1371/journal.pone.0027976.t005.
Table 5  Age-stratified Longitudinal Analysis of Hypertension Stages and Pulse Pressure Tertiles on Cognitive Decline.
Ages 70–75 (n = 248)
HTN I HTN II PP Middle Tertile PP Upper Tertile
HR (95% CI) HR (95% CI) HR (95% CI) HR (95% CI)
HVLT-D
Unadjusted 1.46 (0.74–2.87) 1.05 (0.49–2.27) 1.06 (0.54–2.07) 1.08 (0.55–2.11)
Model 1 1.40 (0.71–2.76) 0.91 (0.42–1.99) 1.15 (0.58–2.31) 1.25 (0.61–2.60)
Model 2 1.39 (0.68–2.84) 0.88 (0.39–2.02) 0.99 (0.47–2.09) 1.32 (0.63–2.78)
HVLT-I
Unadjusted 1.57 (0.78–3.13) 1.48 (0.70–3.14) 1.92 (0.96–3.87) 1.77 (0.87–3.58)
Model 1 1.52 (0.76–3.03) 1.28 (0.60–2.72) 2.58 (1.24–5.36)** 2.65 (1.21–5.80)*
Model 2 1.47 (0.71–3.02) 1.21 (0.55–2.66) 2.44 (1.11–5.39)* 3.13 (1.35–7.24)**
TMT, Part A
Unadjusted 2.52 (1.07–5.89)* 1.25 (0.45–3.46) 0.78 (0.35–1.73) 0.93 (0.43–1.99)
Model 1 2.38 (1.01–5.57)* 1.08 (0.39–3.00) 1.06 (0.47–2.39) 1.86 (0.81–4.26)
Model 2 2.13 (0.84–5.42) 1.02 (0.35–3.00) 1.01 (0.38–2.68) 1.46 (0.57–3.74)
TMT, Part B
Unadjusted 1.15 (0.61–2.16) 1.05 (0.53–2.07) 0.64 (0.31–1.34) 1.71 (0.95–3.07)
Model 1 1.09 (0.58–2.07) 0.87 (0.43–1.74) 0.68 (0.32–1.45) 1.83 (0.96–3.49)
Model 2 1.01 (0.51–1.99) 1.04 (0.50–2.16) 0.58 (0.25–1.32) 1.83 (0.91–3.71)
MMSE
Unadjusted 0.65 (0.25–1.70) 1.43 (0.60–3.41) 0.97 (0.40–2.33) 0.98 (0.41–2.37)
Model 1 0.56 (0.22–1.47) 1.02 (0.43–2.46) 1.02 (0.42–2.49) 1.00 (0.38–2.60)
Model 2 0.47 (0.17–1.30) 1.07 (0.41–2.80) 1.03 (0.39–2.72) 0.97 (0.34–2.73)
Ages 76–80 (n = 88)
HTN I HTN II PP Middle Tertile PP Upper Tertile
HR (95% CI) HR (95% CI) HR (95% CI) HR (95% CI)
HVLT-D
Unadjusted 0.93 (0.39–2.25) 0.88 (0.39–2.00) 0.65 (0.27–1.55) 0.79 (0.34–1.83)
Model 1 0.85 (0.35–2.08) 0.92 (0.40–2.08) 0.64 (0.26–1.56) 0.79 (0.33–1.90)
Model 2 0.82 (0.27–2.47) 1.13 (0.38–3.43) 0.80 (0.27–2.31) 2.08 (0.54–7.98)
HVLT-I
Unadjusted 0.85 (0.38–1.91) 0.59 (0.27–1.30) 0.82 (0.37–1.81) 0.51 (0.21–1.20)
Model 1 0.81 (0.36–1.84) 0.61 (0.28–1.35) 0.80 (0.36–1.79) 0.47 (0.19–1.16)
Model 2 0.96 (0.38–2.45) 0.98 (0.37–2.59) 0.68 (0.27–1.71) 0.86 (0.25–2.93)
TMT, Part A
Unadjusted 0.68 (0.24–1.93) 1.15 (0.49–2.69) 0.77 (0.29–2.06) 1.03 (0.40–2.61)
Model 1 0.65 (0.23–1.85) 1.18 (0.50–2.76) 0.81 (0.29–2.24) 1.08 (0.40–2.94)
Model 2 0.80 (0.22–2.97) 2.56 (0.73–9.06) 0.52 (0.15–1.87) 2.01 (0.49–8.28)
TMT, Part B
Unadjusted 1.26 (0.52–3.03) 1.30 (0.59–2.88) 0.75 (0.31–1.79) 0.95 (0.41–2.18)
Model 1 1.20 (0.50–2.89) 1.39 (0.62–3.11) 0.74 (0.30–1.81) 1.05 (0.42–2.65)
Model 2 2.13 (0.65–6.95) 5.05 (1.42–18.04)* 1.24 (0.36–4.28) 5.12 (1.11–23.62)*
MMSE
Unadjusted -# -# 0.74 (0.23–2.44) 1.37 (0.47–4.02)
Model 1 -# -# 1.11 (0.30–4.09) 1.89 (0.58–6.19)
Model 2 -# -# 0.83 (0.20–3.47) 2.36 (0.40–13.83)

Reference group for HTN: Control group (SBP≤139 mmHg): for PP: pulse pressure lower tertile (48–68 mmHg).

HTN Stage I = Hypertension Stage I (SBP 140–159 mmHg); HTN Stage II = Hypertension Satge II (SBP≥160); PP middle tertile = Pulse pressure 71–77 mmHg, and PP upper tertile = Pulse pressure 84–108 mmHg.

Model 1: age, race, education.

Model 2: age, race, education, history of high blood pressure, stroke, myocardial infarction, congestive heart failure, peripheral artery disease, diabetes mellitus, angina; history of smoking, BMI, ever on hypertensive medication, glucose, cholesterol, and depression score.

Note: All Trails B models adjust for Trails A performance.

MMSE = Mini Mental State Exam; TMT, Part A = Trail Making Test, Part A; TMT, Part B = Trail Making Test, Part B; HVLT = Hopkins Verbal Learning Test (HVLT-I = immediate recall; HVLT-D = delayed recall);

*p-value<0.05.

**p-value<0.01.



Article Categories:
  • Research Article
Article Categories:
  • Biology
    • Neuroscience
      • Cognitive Neuroscience
        • Cognition
Article Categories:
  • Medicine
    • Cardiovascular
      • Cardiovascular Diseases in Women
      • Hypertension
    • Mental Health
      • Psychology
        • Cognitive Psychology
          • Learning
    • Nephrology
      • Hypertension
    • Neurology
      • Cognitive Neurology
    • Women's Health
      • Cardiovascular Diseases in Women
Article Categories:
  • Social and Behavioral Sciences
    • Psychology
      • Cognitive Psychology
        • Learning


Previous Document:  Diverging mechanisms of activation of chemokine receptors revealed by novel chemokine agonists.
Next Document:  Roles of the DYRK kinase Pom2 in cytokinesis, mitochondrial morphology, and sporulation in fission y...