Association of Midlife to Late-Life Blood Pressure Patterns With Incident Dementia | Dementia and Cognitive Impairment | JAMA | JAMA Network
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This video summarizes findings from 2 studies investigating high blood pressure and dementia. The first, a 2019 SPRINT MIND substudy, reports reduction in MRI-measured white matter hyperintensities, a radiographic sign of vascular damage and known risk factor for cognitive decline and dementia. The second, from the Atherosclerotic Risk in Communities (ARIC) population cohort, shows an association between midlife hypertension and longer-term dementia.

Walker  KA, Power  MC, Gottesman  RF.  Defining the relationship between hypertension, cognitive decline, and dementia: a review.  Curr Hypertens Rep. 2017;19(3):24. doi:10.1007/s11906-017-0724-3PubMedGoogle ScholarCrossref
Gottesman  RF, Schneider  ALC, Albert  M,  et al.  Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study.  JAMA Neurol. 2014;71(10):1218-1227. doi:10.1001/jamaneurol.2014.1646PubMedGoogle ScholarCrossref
Gottesman  RF, Schneider  ALC, Zhou  Y,  et al.  Association between midlife vascular risk factors and estimated brain amyloid deposition.  JAMA. 2017;317(14):1443-1450. doi:10.1001/jama.2017.3090PubMedGoogle ScholarCrossref
Muller  M, Sigurdsson  S, Kjartansson  O,  et al.  Joint effect of mid- and late-life blood pressure on the brain.  Neurology. 2014;82(24):2187-2195.PubMedGoogle ScholarCrossref
Glodzik  L, Rusinek  H, Pirraglia  E,  et al.  Blood pressure decrease correlates with tau pathology and memory decline in hypertensive elderly.  Neurobiol Aging. 2014;35(1):64-71.PubMedGoogle ScholarCrossref
Power  MC, Schneider  ALC, Wruck  L,  et al.  Life-course blood pressure in relation to brain volumes.  Alzheimers Dement. 2016;12(8):890-899.PubMedGoogle ScholarCrossref
The ARIC Investigators.  The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives.  Am J Epidemiol. 1989;129(4):687-702.PubMedGoogle ScholarCrossref
Zhang  Y-P, Zuo  X-C, Huang  Z-J,  et al.  The impact of blood pressure on kidney function in the elderly.  Kidney Blood Press Res. 2013;38(2-3):205-216.PubMedGoogle ScholarCrossref
Oyetunji  TA, Chang  DC, Crompton  JG,  et al.  Redefining hypotension in the elderly.  Arch Surg. 2011;146(7):865-869.PubMedGoogle ScholarCrossref
Gould  CE, Beaudreau  SA.  Association between depression and anxiety on blood pressure dysregulation and pulse in the Health and Retirement Study.  Int J Geriatr Psychiatry. 2013;28(10):1045-1053. doi:10.1002/gps.3926PubMedGoogle ScholarCrossref
Knopman  DS, Gottesman  RF, Sharrett  AR,  et al.  Mild cognitive impairment and dementia prevalence.  Alzheimers Dement (Amst). 2016;2:1-11.PubMedGoogle Scholar
Hayden  KM, Reed  BR, Manly  JJ,  et al.  Cognitive decline in the elderly.  Age Ageing. 2011;40(6):684-689.PubMedGoogle ScholarCrossref
Wilson  RS, Li  Y, Bienias  JL, Bennett  DA.  Cognitive decline in old age.  Psychol Aging. 2006;21(4):774-789.PubMedGoogle ScholarCrossref
McKhann  GM, Knopman  DS, Chertkow  H,  et al.  The diagnosis of dementia due to Alzheimer’s disease.  Alzheimers Dement. 2011;7(3):263-269.PubMedGoogle ScholarCrossref
American Psychiatric Association.  DSM-5: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
Carpenter  CR, DesPain  B, Keeling  TN, Shah  M, Rothenberger  M.  The Six-Item Screener and AD8 for the detection of cognitive impairment in geriatric emergency department patients.  Ann Emerg Med. 2011;57(6):653-661.PubMedGoogle ScholarCrossref
Galvin  JE, Roe  CM, Xiong  C, Morris  JC.  Validity and reliability of the AD8 informant interview in dementia.  Neurology. 2006;67(11):1942-1948.PubMedGoogle ScholarCrossref
Schneider  ALC, Sharrett  AR, Gottesman  RF,  et al.  Normative data for 8 neuropsychological tests in older blacks and whites from the atherosclerosis risk in communities (ARIC) study.  Alzheimer Dis Assoc Disord. 2015;29(1):32-44.PubMedGoogle ScholarCrossref
Gross  AL, Power  MC, Albert  MS,  et al.  Application of latent variable methods to the study of cognitive decline when tests change over time.  Epidemiology. 2015;26(6):878-887.PubMedGoogle ScholarCrossref
Gottesman  RF, Albert  MS, Alonso  A,  et al.  Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) cohort.  JAMA Neurol. 2017;74(10):1246-1254.PubMedGoogle ScholarCrossref
Siedel  J, Hägele  EO, Ziegenhorn  J, Wahlefeld  AW.  Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency.  Clin Chem. 1983;29(6):1075-1080.PubMedGoogle Scholar
Warnick  GR, Benderson  J, Albers  JJ.  Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol.  Clin Chem. 1982;28(6):1379-1388.PubMedGoogle Scholar
Reitz  C, Tang  M-X, Manly  J, Mayeux  R, Luchsinger  JA.  Hypertension and the risk of mild cognitive impairment.  Arch Neurol. 2007;64(12):1734-1740. doi:10.1001/archneur.64.12.1734PubMedGoogle ScholarCrossref
Pandav  R, Dodge  HH, DeKosky  ST, Ganguli  M.  Blood pressure and cognitive impairment in India and the United States.  Arch Neurol. 2003;60(8):1123-1128.PubMedGoogle ScholarCrossref
Power  MC, Weuve  J, Gagne  JJ,  et al.  The association between blood pressure and incident Alzheimer disease.  Epidemiology. 2011;22(5):646-659.PubMedGoogle ScholarCrossref
Power  MC, Tchetgen  EJT, Sparrow  D, Schwartz  J, Weisskopf  MG.  Blood pressure and cognition.  Epidemiology. 2013;24(6):886-893.PubMedGoogle ScholarCrossref
Swan  GE, Carmelli  D, Larue  A.  Systolic blood pressure tracking over 25 to 30 years and cognitive performance in older adults.  Stroke. 1998;29(11):2334-2340. doi:10.1161/01.STR.29.11.2334PubMedGoogle ScholarCrossref
Skoog  I, Lernfelt  B, Landahl  S,  et al.  15-Year longitudinal study of blood pressure and dementia.  Lancet. 1996;347(9009):1141-1145.PubMedGoogle ScholarCrossref
Qiu  C, von Strauss  E, Winblad  B, Fratiglioni  L.  Decline in blood pressure over time and risk of dementia.  Stroke. 2004;35(8):1810-1815.PubMedGoogle ScholarCrossref
Ferrari  AU.  Modifications of the cardiovascular system with aging.  Am J Geriatr Cardiol. 2002;11(1):30-33. doi:10.1111/1467-8446.00044-i1PubMedGoogle ScholarCrossref
Zlokovic  BV.  Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders.  Nat Rev Neurosci. 2011;12(12):723-738. doi:10.1038/nrn3114PubMedGoogle ScholarCrossref
Glodzik  L, Rusinek  H, Tsui  W,  et al.  Different relationship between systolic blood pressure and cerebral perfusion in subjects with and without hypertension.  Hypertension. 2019;73(1):197-205.PubMedGoogle ScholarCrossref
Muller  M, van der Graaf  Y, Visseren  FL,  et al.  Hypertension and longitudinal changes in cerebral blood flow.  Ann Neurol. 2012;71(6):825-833.PubMedGoogle ScholarCrossref
Koike  MA, Green  KN, Blurton-Jones  M, Laferla  FM.  Oligemic hypoperfusion differentially affects tau and amyloid-beta.  Am J Pathol. 2010;177(1):300-310. doi:10.2353/ajpath.2010.090750PubMedGoogle ScholarCrossref
Gentile  MT, Poulet  R, Di Pardo  A,  et al.  Beta-amyloid deposition in brain is enhanced in mouse models of arterial hypertension.  Neurobiol Aging. 2009;30(2):222-228.PubMedGoogle ScholarCrossref
Wright  JT  Jr, Williamson  JD, Whelton  PK,  et al.  A randomized trial of intensive versus standard blood-pressure control.  N Engl J Med. 2015;373(22):2103-2116.PubMedGoogle ScholarCrossref
Original Investigation
August 13, 2019

Association of Midlife to Late-Life Blood Pressure Patterns With Incident Dementia

Author Affiliations
  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 3School of Public Health, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis
  • 4Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 5Johns Hopkins Center on Aging and Health, Baltimore, Maryland
  • 6Division of Geriatrics, Department of Medicine, University of Mississippi Medical Center, Jackson
  • 7Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 8Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health, Washington, DC
JAMA. 2019;322(6):535-545. doi:10.1001/jama.2019.10575
Key Points

Question  Are specific midlife to late-life longitudinal blood pressure patterns associated with increased risk of dementia among older adults?

Finding  In this prospective cohort study that included 4761 participants with 24-year follow-up and blood pressure measurements at midlife and at late life, those with midlife and late-life hypertension (hazard ratio, 1.49) and those with midlife hypertension and late-life hypotension (hazard ratio, 1.62) had higher risk for incident dementia compared with those who remained normotensive.

Meaning  Patterns of blood pressure in midlife and late life may be associated with differing risks for incident dementia.


Importance  The association between late-life blood pressure (BP) and cognition may depend on the presence and chronicity of past hypertension. Late-life declines in blood pressure following prolonged hypertension may be associated with poor cognitive outcomes.

Objective  To examine the association of midlife to late-life BP patterns with subsequent dementia, mild cognitive impairment, and cognitive decline.

Design, Setting, and Participants  The Atherosclerosis Risk in Communities prospective population-based cohort study enrolled 4761 participants during midlife (visit 1, 1987-1989) and followed-up over 6 visits through 2016-2017 (visit 6). BP was examined over 24 years at 5 in-person visits between visits 1 and 5 (2011-2013). During visits 5 and 6, participants underwent detailed neurocognitive evaluation. The setting was 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Follow-up ended on December 31, 2017.

Exposures  Five groups based on longitudinal patterns of normotension, hypertension (>140/90 mm Hg), and hypotension (<90/60 mm Hg) at visits 1 to 5.

Main Outcomes and Measures  Primary outcome was dementia onset after visit 5, based on Ascertain Dementia-8 informant questionnaires, Six-Item Screener telephone assessments, hospital discharge and death certificate codes, and the visit 6 neurocognitive evaluation. Secondary outcome was mild cognitive impairment at visit 6, based on the neurocognitive evaluation.

Results  Among 4761 participants (2821 [59%] women; 979 [21%] black race; visit 5 mean [SD] age, 75 [5] years; visit 1 mean age range, 44-66 years; visit 5 mean age range, 66-90 years), there were 516 (11%) incident dementia cases between visits 5 and 6. The dementia incidence rate for participants with normotension in midlife (n = 833) and late life was 1.31 (95% CI, 1.00-1.72 per 100 person-years); for midlife normotension and late-life hypertension (n = 1559), 1.99 (95% CI, 1.69-2.32 per 100 person-years); for midlife and late-life hypertension (n = 1030), 2.83 (95% CI, 2.40-3.35 per 100 person-years); for midlife normotension and late-life hypotension (n = 927), 2.07 (95% CI, 1.68-2.54 per 100 person-years); and for midlife hypertension and late-life hypotension (n = 389), 4.26 (95% CI, 3.40-5.32 per 100 person-years). Participants in the midlife and late-life hypertension group (hazard ratio [HR], 1.49 [95% CI, 1.06-2.08]) and in the midlife hypertension and late-life hypotension group (HR, 1.62 [95% CI, 1.11-2.37]) had significantly increased risk of subsequent dementia compared with those who remained normotensive. Irrespective of late-life BP, sustained hypertension in midlife was associated with dementia risk (HR, 1.41 [95% CI, 1.17-1.71]). Compared with those who were normotensive in midlife and late life, only participants with midlife hypertension and late-life hypotension had higher risk of mild cognitive impairment (37 affected individuals (odds ratio, 1.65 [95% CI, 1.01-2.69]). There was no significant association of BP patterns with late-life cognitive change.

Conclusions and Relevance  In this community-based cohort with long-term follow-up, sustained hypertension in midlife to late life and a pattern of midlife hypertension and late-life hypotension, compared with midlife and late-life normal BP, were associated with increased risk for subsequent dementia.