Prehypertensive Blood Pressures and Regional Cerebral Blood Flow Independently Relate to Cognitive Performance in Midlife

Background High blood pressure is thought to contribute to dementia in late life, but our understanding of the relationship between individual differences in blood pressure (BP) and cognitive functioning is incomplete. In this study, cognitive performance in nonhypertensive midlife adults was examined as a function of resting BP and regional cerebral blood flow (rCBF) responses during cognitive testing. We hypothesized that BP would be negatively related to cognitive performance and that cognitive performance would also be related to rCBF responses within areas related to BP control. We explored whether deficits related to systolic BP might be explained by rCBF responses to mental challenge. Methods and Results Healthy midlife participants (n=227) received neuropsychological testing and performed cognitive tasks in a magnetic resonance imaging scanner. A pseudocontinuous arterial spin labeling sequence assessed rCBF in brain areas related to BP in prior studies. Systolic BP was negatively related to 4 of 5 neuropsychological factors (standardized β>0.13): memory, working memory, executive function, and mental efficiency. The rCBF in 2 brain regions of interest was similarly related to memory, executive function, and working memory (standardized β>0.17); however, rCBF responses did not explain the relationship between resting systolic BP and cognitive performance. Conclusions Relationships at midlife between prehypertensive levels of systolic BP and both cognitive and brain function were modest but suggested the possible value of midlife intervention.

[1]  R. Vasan,et al.  Association of Aortic Stiffness With Cognition and Brain Aging in Young and Middle-Aged Adults: The Framingham Third Generation Cohort Study , 2016, Hypertension.

[2]  K. Sink,et al.  Hypertension and Its Role in Cognitive Function: Current Evidence and Challenges for the Future. , 2016, American journal of hypertension.

[3]  S. Villapol,et al.  Neuroprotective effects of angiotensin receptor blockers. , 2015, American journal of hypertension.

[4]  Peter J Gianaros,et al.  Anterior cingulate activity correlates with blood pressure during stress. , 2005, Psychophysiology.

[5]  A. Verberne,et al.  Cortical Modulation of theCardiovascular System , 1998, Progress in Neurobiology.

[6]  A. Verberne Modulation of Autonomic Function by the Cerebral Cortex , 2011 .

[7]  Peter L. Strick,et al.  Motor, cognitive, and affective areas of the cerebral cortex influence the adrenal medulla , 2016, Proceedings of the National Academy of Sciences.

[8]  L. Fried,et al.  Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. , 1996, Stroke.

[9]  Christos Davatzikos,et al.  Vascular Factors and Multiple Measures of Early Brain Health: CARDIA Brain MRI Study , 2015, PloS one.

[10]  Gerd Wagner,et al.  Functional connectivity and network analysis of midbrain and brainstem nuclei , 2016, NeuroImage.

[11]  Julian F. Thayer,et al.  Nonlinear Relations of Blood Pressure to Cognitive Function: The Baltimore Longitudinal Study of Aging , 2005, Hypertension.

[12]  Peter J. Gianaros,et al.  Higher blood pressure predicts lower regional grey matter volume: Consequences on short-term information processing , 2006, NeuroImage.

[13]  Intermanual differences on skilled and unskilled motor tasks in nonlateralized brain dysfunction , 1992 .

[14]  G. Bush,et al.  The Multi-Source Interference Task: an fMRI task that reliably activates the cingulo-frontal-parietal cognitive/attention network , 2006, Nature Protocols.

[15]  J. Price,et al.  Cerebrovascular Support for Cognitive Processing in Hypertensive Patients Is Altered by Blood Pressure Treatment , 2008, Hypertension.

[16]  Peter J. Gianaros,et al.  A review of neuroimaging studies of stressor-evoked blood pressure reactivity: Emerging evidence for a brain-body pathway to coronary heart disease risk , 2009, NeuroImage.

[17]  L. Morrow,et al.  Normative Data for a Working Memory Test: the Four Word Short-Term Memory Test , 2002, The Clinical neuropsychologist.

[18]  J. Murabito,et al.  Midlife Hypertension Risk and Cognition in the Non-Demented Oldest Old: Framingham Heart Study. , 2015, Journal of Alzheimer's disease : JAD.

[19]  D. Alsop,et al.  Continuous flow‐driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields , 2008, Magnetic resonance in medicine.

[20]  A. Toga,et al.  Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline , 2015, American Journal of Neuroradiology.

[21]  H. E. King,et al.  Hypertension: Cognitive and behavioral considerations , 1990, Neuropsychology Review.

[22]  Owen T. Carmichael,et al.  Abnormal Regional Cerebral Blood Flow in Cognitively Normal Elderly Subjects With Hypertension , 2008, Stroke.

[23]  S. Manuck,et al.  Hypertension and neuropsychological performance in men: interactive effects of age. , 1996, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[24]  J. Jennings,et al.  Test-retest reliability of an fMRI paradigm for studies of cardiovascular reactivity. , 2012, Psychophysiology.

[25]  L. Launer,et al.  Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: A systematic review and meta-analysis , 2015, Neuroscience & Biobehavioral Reviews.

[26]  S. Redline,et al.  Recognition and consequences of obstructive sleep apnea hypopnea syndrome. , 1999, Clinics in chest medicine.

[27]  S. Black,et al.  Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association , 2011, Stroke.

[28]  J. P. Card,et al.  Central Autonomic Pathways , 2011 .

[29]  J. Detre,et al.  Arterial spin labeling perfusion fMRI with very low task frequency , 2003, Magnetic resonance in medicine.

[30]  J. Price,et al.  Reduced cerebral blood flow response and compensation among patients with untreated hypertension , 2005, Neurology.

[31]  Peter J Gianaros,et al.  Heightened Functional Neural Activation to Psychological Stress Covaries With Exaggerated Blood Pressure Reactivity , 2007, Hypertension.

[32]  A. Dorrance,et al.  The effects of hypertension on the cerebral circulation. , 2013, American journal of physiology. Heart and circulatory physiology.

[33]  Sudha Seshadri,et al.  Impact of Hypertension on Cognitive Function: A Scientific Statement From the American Heart Association , 2016, Hypertension.

[34]  David R. Williams,et al.  Blood Pressure Reactivity to Psychological Stress Predicts Hypertension in the CARDIA Study , 2004, Circulation.

[35]  A. Sved,et al.  Brainstem mechanisms of hypertension: Role of the rostral ventrolateral medulla , 2003, Current hypertension reports.

[36]  S. Manuck,et al.  Neuropsychological performance of young men who vary in familial risk for hypertension. , 1994, Psychosomatic medicine.

[37]  L. Ferrucci,et al.  Baseline Cardiovascular Risk Predicts Subsequent Changes in Resting Brain Function , 2012, Stroke.

[38]  S. Manuck,et al.  Neuropsychological correlates of hypertension: review and methodologic considerations. , 1991, Psychological bulletin.

[39]  P. Guyenet The sympathetic control of blood pressure , 2006, Nature Reviews Neuroscience.

[40]  S Warach,et al.  A general kinetic model for quantitative perfusion imaging with arterial spin labeling , 1998, Magnetic resonance in medicine.

[41]  M. Elias,et al.  Hypertension and cognitive functioning: a perspective in historical context. , 2012, Hypertension.

[42]  V. Napadow,et al.  The Autonomic Brain: An Activation Likelihood Estimation Meta-Analysis for Central Processing of Autonomic Function , 2013, The Journal of Neuroscience.

[43]  C. Lewis,et al.  Blood Pressure Reactivity to Psychological Stress in Young Adults and Cognition in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study , 2016, Journal of the American Heart Association.

[44]  M. Mintun,et al.  Cerebral blood flow in hypertensive patients: an initial report of reduced and compensatory blood flow responses during performance of two cognitive tasks. , 1998, Hypertension.

[45]  H. Aizenstein,et al.  Regional grey matter shrinks in hypertensive individuals despite successful lowering of blood pressure , 2011, Journal of Human Hypertension.

[46]  G. Bakris,et al.  Hypertension: A Companion to Braunwald's Heart Disease , 2017 .

[47]  E. Benarroch The central autonomic network: functional organization, dysfunction, and perspective. , 1993, Mayo Clinic proceedings.

[48]  Henry R. Black,et al.  Hypertension Primer: The Essentials of High Blood Pressure , 1993 .

[49]  Federica Scarpina,et al.  The Stroop Color and Word Test , 2017, Front. Psychol..

[50]  A. Gabor,et al.  Central neuromodulatory pathways regulating sympathetic activity in hypertension. , 2012, Journal of applied physiology.

[51]  N. Schneiderman,et al.  Cardiovascular Reactivity and Development of Preclinical and Clinical Disease States , 2003, Psychosomatic medicine.

[52]  T. Nakagawa,et al.  Pathogenesis of essential hypertension: historical paradigms and modern insights , 2008, Journal of hypertension.

[53]  U. Demkow,et al.  Relevance of Immune-Sympathetic Nervous System Interplay for the Development of Hypertension. , 2015, Advances in experimental medicine and biology.

[54]  D. Harrison The mosaic theory revisited: common molecular mechanisms coordinating diverse organ and cellular events in hypertension. , 2013, Journal of the American Society of Hypertension : JASH.

[55]  Carolyn C. Meltzer,et al.  Verbal and spatial working memory in older individuals: A positron emission tomography study , 2006, Brain Research.

[56]  P. Roche,et al.  Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells , 2015, Front. Physiol..

[57]  I. Hajjar,et al.  The relationship between blood pressure and cognitive function , 2010, Nature Reviews Cardiology.

[58]  D. Carmelli,et al.  Systolic blood pressure tracking over 25 to 30 years and cognitive performance in older adults. , 1998, Stroke.

[59]  J. Trauth,et al.  Validity of a questionnaire to assess historical physical activity in older women. , 2004, Medicine and science in sports and exercise.

[60]  Ahmad R. Hariri,et al.  Individual Differences in Stressor-Evoked Blood Pressure Reactivity Vary with Activation, Volume, and Functional Connectivity of the Amygdala , 2008, The Journal of Neuroscience.

[61]  C. Iadecola Hypertension and dementia. , 2014, Hypertension.

[62]  I. Page The Mosaic Theory of Arterial Hypertension—: Its Interpretation , 2015, Perspectives in biology and medicine.

[63]  T. Kamarck,et al.  A global measure of perceived stress. , 1983, Journal of health and social behavior.

[64]  M. V. van Boxtel,et al.  Temporal Evolution of Cognitive Changes in Incident Hypertension: Prospective Cohort Study Across the Adult Age Span , 2014, Hypertension.

[65]  C. Tzourio,et al.  Is hypertension associated with an accelerated aging of the brain? , 2014, Hypertension.

[66]  R. Reitan Validity of the Trail Making Test as an Indicator of Organic Brain Damage , 1958 .

[67]  G. Jennings,et al.  CHRONIC MENTAL STRESS IS A CAUSE OF ESSENTIAL HYPERTENSION: PRESENCE OF BIOLOGICAL MARKERS OF STRESS , 2008, Clinical and Experimental Pharmacology and Physiology.

[68]  L Bozzao,et al.  Fast spin-echo and fast fluid-attenuated inversion-recovery versus conventional spin-echo sequences for MR quantification of multiple sclerosis lesions. , 1997, AJNR. American journal of neuroradiology.

[69]  Ze Wang,et al.  Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx. , 2008, Magnetic resonance imaging.

[70]  C. Iadecola,et al.  Hypertension: A Harbinger of Stroke and Dementia , 2013, Hypertension.

[71]  J. Richard Jennings,et al.  Is the brain the essential in hypertension? , 2009, NeuroImage.

[72]  S. Manuck,et al.  Is Cardiovascular Reactivity Associated With Atherosclerosis Among Hypertensives? , 2002, Hypertension.

[73]  A. Verberne,et al.  Cortical modulation of the cardiovascular system. , 1998, Progress in neurobiology.

[74]  Christos Davatzikos,et al.  Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network , 2015, NeuroImage.

[75]  R. Dampney The hypothalamus and autonomic regulation: an overview , 2011 .

[76]  G. Martin,et al.  Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults , 2016, Hypertension.

[77]  J. Shoemaker,et al.  Forebrain neurocircuitry associated with human reflex cardiovascular control , 2015, Front. Physiol..

[78]  Tor D Wager,et al.  Brain-Body Pathways Linking Psychological Stress and Physical Health , 2015, Current directions in psychological science.

[79]  J. Price,et al.  Brain Imaging Findings Predict Blood Pressure Response to Pharmacological Treatment , 2008, Hypertension.

[80]  Yaakov Stern,et al.  Cerebral blood flow and gray matter volume covariance patterns of cognition in aging , 2013, Human brain mapping.

[81]  L. Dennerstein,et al.  Prehypertension in midlife is associated with worse cognition a decade later in middle-aged and older women. , 2015, Age and ageing.