Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults

Michael E Ernst, Joanne Ryan, Enayet K Chowdhury, Karen L Margolis, Lawrence J Beilin, Christopher M Reid, Mark R Nelson, Robyn L Woods, Raj C Shah, Suzanne G Orchard, Rory Wolfe, Elsdon Storey, Andrew M Tonkin, Amy Brodtmann, John J McNeil, Anne M Murray, Michael E Ernst, Joanne Ryan, Enayet K Chowdhury, Karen L Margolis, Lawrence J Beilin, Christopher M Reid, Mark R Nelson, Robyn L Woods, Raj C Shah, Suzanne G Orchard, Rory Wolfe, Elsdon Storey, Andrew M Tonkin, Amy Brodtmann, John J McNeil, Anne M Murray

Abstract

Background Blood pressure variability (BPV) in midlife increases risk of late-life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow-up visits. Time-to-event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction P=0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19-2.39) but not women (HR, 1.01; 95% CI, 0.72-1.42). For cognitive decline, similar increased risks were observed for men and women (interaction P=0.15; men: HR, 1.36; 95% CI, 1.16-1.59; women: HR, 1.14; 95% CI, 0.98-1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583; isrctn.com. Identifier: ISRCTN83772183.

Keywords: blood pressure; blood pressure variability; cognitive impairment; dementia.

Conflict of interest statement

None.

Figures

Figure 1. Consort flow diagram of participants…
Figure 1. Consort flow diagram of participants included in the analysis.
ASPREE indicates Aspirin in Reducing Events in the Elderly; BP, blood pressure; and BPV, blood pressure variability.
Figure 2. Cumulative incidence of events according…
Figure 2. Cumulative incidence of events according to blood pressure variability tertile; dementia incidence in men (A); dementia incidence in women (B); incidence of cognitive decline in men (C); and incidence of cognitive decline in women (D).
BPV indicates blood pressure variability; and T, tertile.

References

    1. United Nations, Department of Economic and Social Affairs, Population Division . World Population Ageing 2017—Highlights (ST/ESA/SER.A/397). 2017.
    1. Gottesman RF, Schneider ALC, Albert M, Alonso A, Bandeen‐Roche K, Coker L, Coresh J, Knopman D, Power MC, Rawlings A, et al. Midlife hypertension and 20‐year cognitive change: the Atherosclerosis Risk in Communities Neurocognitive Study. JAMA Neurol. 2014;71:1218–1227. DOI: 10.1001/jamaneurol.2014.1646.
    1. Ou YN, Tan CC, Shen XN, Xu W, Hou XH, Dong Q, Tan L, Yu JT. Blood pressure and risks of cognitive impairment and dementia: a systematic review and meta‐analysis of 209 prospective studies. Hypertension. 2020;76:217–225. DOI: 10.1161/HYPERTENSIONAHA.120.14993.
    1. Walker KA, Sharrett AR, Wu A, Schneider ALC, Albert M, Lutsey PL, Bandeen‐Roche K, Coresh J, Gross AL, Windham BG, et al. Association of midline to late‐life blood pressure patterns with incident dementia. JAMA. 2019;322:535–545.
    1. Abell JG, Kivimäki M, Dugravot A, Tabak AG, Fayosse A, Shipley M, Sabia S, Singh‐Manoux A. Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration, and threshold used to define hypertension. Eur Heart J. 2018;39:3119–3125. DOI: 10.1093/eurheartj/ehy288.
    1. Levine DA, Galecki AT, Langa KM, Unverzagt FW, Kabeto MU, Giordani B, Cushman M, McClure LA, Safford MM, Wadley VG. Blood pressure and cognitive decline over 8 years in middle‐aged and older black and white Americans. Hypertension. 2019;73:310–318. DOI: 10.1161/HYPERTENSIONAHA.118.12062.
    1. Rouch L, Cestac P, Hanon O, Ruidavets J‐B, Ehlinger V, Gentil C, Cool C, Helmer C, Dartigues J‐F, Bouhanick B, et al. Blood pressure and cognitive performances in middle‐aged adults: the aging, health and work longitudinal study. J Hypertens. 2019;37:1244–1253. DOI: 10.1097/HJH.0000000000002013.
    1. Oishi E, Ohara T, Sakata S, Fukuhara M, Hata J, Yoshida D, Shibata M, Ohtsubo T, Kitazono T, Kiyohara Y, et al. Day‐to‐day blood pressure variability and risk of dementia in a general Japanese elderly population. Circulation. 2017;136:516–525. DOI: 10.1161/CIRCULATIONAHA.116.025667.
    1. Zhou TL, Kroon AA, van Sloten TT, van Boxtel MPJ, Verhey FRJ, Schram MT, Köhler S, Stehouwer CDA, Henry RMA. Greater blood pressure variability is associated with lower cognitive performance. Hypertension. 2019;73:803–811. DOI: 10.1161/HYPERTENSIONAHA.118.12305.
    1. Yoo JE, Shin DW, Han K, Kim D, Lee SP, Jeong SM, Lee J, Kim S. Blood pressure variability and the risk of dementia. Hypertension. 2020;75:982–990. DOI: 10.1161/HYPERTENSIONAHA.119.14033.
    1. Qin B, Viera AJ, Muntner P, Plassman BL, Edwards LJ, Adair LS, Popkin BM, Mendez MA. Visit‐to‐visit variability in blood pressure is related to late‐life cognitive decline. Hypertension. 2016;68:106–113. DOI: 10.1161/HYPERTENSIONAHA.116.07494.
    1. Nagai M, Hoshide S, Ishikawa J, Shimada K, Kario K. Visit‐to‐visit blood pressure variations: new independent determinants for cognitive function in the elderly at high risk of cardiovascular disease. J Hypertens. 2012;30:1556–1563. DOI: 10.1097/HJH.0b013e3283552735.
    1. Sabayan B, Wijsman LW, Foster‐Dingley JC, Stott DJ, Ford I, Buckley BM, Sattar N, Jukema JW, van Osch MJP, van der Grond J, et al. Association of visit‐to‐visit variability in blood pressure with cognitive function in old age: prospective cohort study. BMJ. 2013;347:f4600. DOI: 10.1136/bmj.f4600.
    1. Böhm M, Schumacher H, Leong D, Mancia G, Unger T, Schmieder R, Custodis F, Diener H‐C, Laufs U, Lonn E, et al. Systolic blood pressure variation and mean heart rate is associated with cognitive dysfunction in patients with high cardiovascular risk. Hypertension. 2015;65:651–661. DOI: 10.1161/HYPERTENSIONAHA.114.04568.
    1. Epstein NU, Lane KA, Farlow MR, Risacher SL, Saykin AJ, Gao S; Alzheimer’s Disease Neuroimaging Initiative . Cognitive dysfunction and greater visit‐to‐visit systolic blood pressure variability. J Am Geriatr Soc. 2013;61:2168–2173. DOI: 10.1111/jgs.12542.
    1. de Heus RAA, Olde Rikkert MGM, Tully PJ, Lawlor BA, Classen JAHR; NILVAD Study Group . Blood pressure variability and progression of clinical Alzheimer disease. Hypertension. 2019;74:1172–1180. DOI: 10.1161/HYPERTENSIONAHA.119.13664.
    1. Kronish IM, Kent S, Moise N, Shimbo D, Safford MM, Kynerd RE, O’Beirne R, Sullivan A, Muntner P. Barriers to conducting ambulatory and home blood pressure monitoring during hypertension screening in the United States. J Am Soc Hypertens. 2017;11:573–580. DOI: 10.1016/j.jash.2017.06.012.
    1. Parati G, Stergiou GS, Dolan E, Bilo G. Blood pressure variability: clinical relevance and application. J Clin Hypertens. 2018;20:1133–1137. DOI: 10.1111/jch.13304.
    1. Nelson MR; ASPREE Investigator Group . Study design of ASPirin in Reducing Events in the Elderly (ASPREE): a randomized, controlled trial. Contemp Clin Trials. 2013;36:555–564. DOI: 10.1016/j.cct.2013.09.014.
    1. McNeil JJ, Woods RL, Nelson MR, Murray AM, Reid CM, Kirpach B, Storey E, Shah RC, Wolfe RS, Tonkin AM, et al. Baseline characteristics of participants in the ASPREE (ASPirin in Reducing Events in the Elderly) study. J Gerontol A Biol Sci Med Sci. 2017;72:1586–1593. DOI: 10.1093/gerona/glw342.
    1. McNeil JJ, Woods RL, Nelson MR, Reid CM, Kirpach B, Wolfe R, Storey E, Shah RC, Lockery JE, Tonkin AM, et al. Effect of aspirin on disability‐free survival in the healthy elderly. N Engl J Med. 2018;379:1499–1508. DOI: 10.1056/NEJMoa1800722.
    1. Ryan J, Storey E, Murray AM, Woods RL, Wolfe R, Reid CM, Nelson MR, Chong TTJ, Williamson JD, Ward SA, et al. Randomized placebo‐controlled trial of the effects of aspirin on dementia and cognitive decline. Neurology. 2020;95:e320–e331. DOI: 10.1212/WNL.0000000000009277.
    1. Ryan J, Woods RL, Britt C, Murray AM, Shah RC, Reid CM, Kirpach B, Wolfe RS, Nelson MR, Lockery JE, et al. Normative performance of healthy older individuals on the Modified Mini‐Mental State (3MS) examination according to ethno‐racial group, gender, age, and education level. Clin Neuropsychol. 2018;33:779–797. DOI: 10.1080/13854046.2018.1488996.
    1. Benedict RHB, Schretlen D, Groninger L, Brandt J. Hopkins Verbal Learning Test–Revised: normative data and analysis of inter‐form and test‐retest reliability. Clin Neuropsychol. 2001;12:43–55. DOI: 10.1076/clin.12.1.43.1726.
    1. Ross TP. The reliability of cluster and switch scores for the Controlled Oral Word Association Test. Arch Clin Neuropsychol. 2003;18:153–164. DOI: 10.1093/arclin/18.2.153.
    1. Smith A. Symbol Digit Modalities Test (SDMT) Manual (Revised). Los Angeles: Western Psychological Services; 1982.
    1. Pickering TG, Hall JE, Appel LJ, Falkner B, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ; Subcommittee of Professional and Public Education of the American Heart Association on High Blood Pressure Research . Recommendations for blood pressure measurement in humans and experimental animals, part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension. 2005;45:142–161. DOI: 10.1161/01.HYP.0000150859.47929.8e.
    1. Graham DP, Cully JA, Snow AL, Massman P, Doody R. The Alzheimer’s Disease Assessment Scale‐Cognitive subscale: normative data for older adult controls. Alzheimer Dis Assoc Disord. 2004;18:236–240.
    1. D’Elia L. Color Trails Test: Professional Manual. Odessa, FL: Psychological Assessment Resources; 1996.
    1. Alegret M, Boada‐Rovira M, Vinyes‐Junqué G, Valero S, Espinosa A, Hernández I, Modinos G, Rosende‐Roca M, Mauleón A, Becker JT, et al. Detection of visuoperceptual deficits in preclinical and mild Alzheimer’s disease. J Clin Exp Neuropsychol. 2009;31:860–867. DOI: 10.1080/13803390802595568.
    1. Fish J. Alzheimer’s disease cooperative study ADL scale. In: Kreutzer JS, DeLuca J, Caplan B, eds. Encyclopedia of Clinical Neuropsychology. New York, NY: Springer; 2011. DOI: 10.1007/978-0-387-79948-3_1791.
    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV). Washington, DC: American Psychiatric Association; 1994.
    1. Lévesque LE, Hanley JA, Kezouh A, Suissa S. Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ. 2010;e340:b5087. DOI: 10.1136/bmj.b5087.
    1. Wijsman LW, de Craen AJM, Muller M, Sabayan B, Stott D, Ford I, Trompet S, Jukema JW, Westendorp RGJ, Mooijaart SP. Blood pressure lowering medication, visit‐to‐visit blood pressure variability, and cognitive function in older age. Am J Hypertens. 2016;29:311–318.
    1. Kronish IM, Lynch AI, Oparil S, Whittle J, Davis BR, Simpson LM, Krousel‐Wood M, Cushman WC, Chang TI, Muntner P. The association between antihypertensive medication nonadherence and visit‐to‐visit variability of blood pressure. Findings from the Antihypertensive and Lipid‐Lowering to Prevent Heart Attack Trial. Hypertension. 2016;68:39–45. DOI: 10.1161/HYPERTENSIONAHA.115.06960.
    1. Rouch L, Cestac P, Sallerin B, Piccoli M, Benattar‐Zibi L, Bertin P, Berrut G, Corruble E, Derumeaux G, Falissard B, et al. Visit‐to‐visit blood pressure variability is associated with cognitive decline and incident dementia. Hypertension. 2020;76:1280–1288. DOI: 10.1161/HYPERTENSIONAHA.119.14553.
    1. Rothwell PM, Howard SC, Dolan E, O’Brien E, Dobson J, Dahlöf B, Sever PS, Poulter NR. Prognostic significance of visit‐to‐visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010;375:895–905. DOI: 10.1016/S0140-6736(10)60308-X.
    1. Muntner P, Shimbo D, Tonelli M, Reynolds K, Arnett DK, Oparil S. The relationship between visit‐to‐visit variability in systolic blood pressure and all‐cause mortality in the general population: findings from NHANES III, 1988 to 1994. Hypertension. 2011;57:160–166. DOI: 10.1161/HYPERTENSIONAHA.110.162255.
    1. Tully PJ, Yano Y, Launer LJ, Kario K, Nagai M, Mooijaart SP, Claassen JAHR, Lattanzi S, Vincent AD, Tzourio C, et al. Variability in Blood Pressure and Brain Health Consortium. Association between blood pressure variability and cerebral small‐vessel disease: a systematic review and meta‐analysis. J Am Heart Assoc. 2020;9:e013841. DOI: 10.1161/JAHA.119.013841.
    1. Lattanzi S, Brigo F, Vernieri F, Silvestreni M. Visit‐to‐visit variability in blood pressure and Alzheimer’s disease. J Clin Hypertens. 2018;20:918–924. DOI: 10.1111/jch.13290.
    1. Ma Y, Yilmaz P, Bos D, Blacker D, Viswanathan A, Ikram MA, Hofman A, Vernooij MW, Ikram MK. Blood pressure variation and subclinical brain disease. J Am Coll Cardiol. 2020;75:2387–2399. DOI: 10.1016/j.jacc.2020.03.043.
    1. de Heus RAA, Reumers SFI, van der Have A, Tumelaire M, Tulley PJ, Claassen JAHR. Day‐to‐day home blood pressure variability is associated with cerebral small vessel disease burden in a memory clinic population. J Alzheimers Dis. 2020;74:463–472. DOI: 10.3233/JAD-191134.
    1. Walker KA, Power MC, Gottesman RF. Defining the relationship between hypertension, cognitive decline, and dementia: a review. Curr Hypertens Rep. 2017;19:24. DOI: 10.1007/s11906-017-0724-3.
    1. Zhong G, Wang Y, Zhang Y, Guo JJ, Zhao Y. Smoking is associated with an increased risk of dementia: a meta‐analysis of prospective cohort studies with investigation of potential effect modifiers. PLoS One. 2015;10:e0118333. DOI: 10.1371/journal.pone.0118333.
    1. Li X, Lyu P, Ren Y, An J, Dong Y. Arterial stiffness and cognitive impairment. J Neurol Sci. 2017;380:1–10. DOI: 10.1016/j.jns.2017.06.018.
    1. Altschul DM, Wraw C, Der G, Gale CR, Deary IJ. Hypertension development by midlife and the roles of premorbid cognitive function, sex, and their interaction. Hypertension. 2019;73:812–819. DOI: 10.1161/HYPERTENSIONAHA.118.12164.
    1. Gilsanz P, Mayeda ER, Glymour MM, Quesenberry CP, Mungas DM, DeCarli C, Dean A, Whitmer RA. Female sex, early‐onset hypertension, and risk of dementia. Neurology. 2017;89:1886–1893. DOI: 10.1212/WNL.0000000000004602.
    1. Robison LS, Gannon OJ, Salinero AE, Zuloaga KL. Contributions of sex to cerebrovascular function and pathology. Brain Res. 2019;1710:43–60. DOI: 10.1016/j.brainres.2018.12.030.
    1. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN III, Assaf AR, Jackson RD, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289:2651–2662. DOI: 10.1001/jama.289.20.2651.
    1. Matyi JM, Rattinger GB, Schwartz S, Buhusi M, Tschanz JT. Lifetime estrogen exposure and cognition in late life: the Cache County Study. Menopause. 2019;26:1366–1374. DOI: 10.1097/GME.0000000000001405.
    1. Ryan J, Carriére I, Scali J, Ritchie K, Ancelin M‐L. Life‐time estrogen exposure and cognitive functioning in later life. Psychoneuroendocrinology. 2009;34:287–298. DOI: 10.1016/j.psyneuen.2008.09.008.
    1. The SPRINT MIND Investigators for the SPRINT Research Group . Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019;321:553–561. DOI: 10.1001/jama.2018.21442.
    1. Volgman AS, Bairey Merz CN, Aggarwal NT, Bittner V, Bunch TJ, Gorelick PB, Maki P, Patel HN, Poppas A, Ruskin J, et al. Sex differences in cardiovascular disease and cognitive impairment: another health disparity for women? J Am Heart Assoc. 2019;8:e013154. DOI: 10.1161/JAHA.119.013154.

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