Blood Pressure Variability and Cognitive Decline. Day-to-Day Variability in Home Blood Pressure Is Associated With Cognitive Decline

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1 Blood Pressure Variability and Cognitive Decline Day-to-Day Variability in Home Blood Pressure Is Associated With Cognitive Decline The Ohasama Study Akihiro Matsumoto,* Michihiro Satoh,* Masahiro Kikuya, Takayoshi Ohkubo, Mikio Hirano, Ryusuke Inoue, Takanao Hashimoto, Azusa Hara, Takuo Hirose, Taku Obara, Hirohito Metoki, Kei Asayama, Aya Hosokawa, Kazuhito Totsune, Haruhisa Hoshi, Toru Hosokawa, Hiroshi Sato, Yutaka Imai See Editorial Commentary, pp 6 65 Abstract Although an association between high blood pressure and cognitive decline has been reported, no studies have investigated the association between home blood pressure and cognitive decline. Home blood pressure measurements can also provide day-to-day blood pressure variability calculated as the within-participant SD. The objectives of this prospective study were to clarify whether home blood pressure has a stronger predictive power for cognitive decline than conventional blood pressure and to compare the predictive power of the averaged home blood pressure with day-to-day home blood pressure variability for cognitive decline. Of 485 participants (mean age, 6 years) who did not have cognitive decline (defined as Mini-Mental State Examination score, <4) initially, 46 developed cognitive decline after a median follow-up of 7.8 years. Each -SD increase in the home systolic blood pressure value showed a significant association with cognitive decline (odds ratio,.48; P=.). However, conventional systolic blood pressure was not significantly associated with cognitive decline (odds ratio,.4; P=.). The day-to-day variability in systolic blood pressure was significantly associated with cognitive decline after including home systolic blood pressure in the same model (odds ratio,.5; P=.), whereas the odds ratio of home systolic blood pressure remained positive, but it was not significant. Home blood pressure measurements can be useful for predicting future cognitive decline because they can provide information not only on blood pressure values but also on day-to-day blood pressure variability. (Hypertension. 4;6:-8.) Online Data Supplement Key Words: blood pressure cohort studies mild cognitive impairment Cognitive impairment resulting from vascular or neurological abnormalities is an important issue for countries with an increasing number of elderly people. As shown in Table of the review by Elias et al, many longitudinal studies reported a positive association between blood pressure (BP) and future cognitive decline., However, most previous prospective studies were based on conventional BP measurements. No studies have investigated the association between home BP and cognitive decline. Home BP measurements are more reproducible, 4 more indicative of target organ damage, 5 and have greater prognostic significance than conventional BP measurements, even when the number of measurements is the same or less when compared with conventional BP measurements. 6 Our recent study, the multicenter Hypertension Objective Treatment Based on Measurement by Electric Devices of BP (HOMED-BP), demonstrated that home BP provided a more reliable estimate of a patient s true BP than conventional BP measurements Received July, ; first decision July 5, ; revision accepted March, 4. From the Department of Clinical Pharmacology and Therapeutics (A.M., T.Hashimoto, H.S.), Department of Preventive Medicine and Epidemiology (M.K., T.Obara), and Department of Community Medical Supports (H.M.), Tohoku Medical Megabank Organization, Department of Planning for Drug Development and Clinical Evaluation (T.Hirose, K.A., K.T., Y.I.), Department of Human Development, Faculty of Education (T.Hosokawa), Tohoku University, Sendai, Japan; Department of Pharmacy (M.S., T.Obara), Medical Information Technology Center (R.I.), Tohoku University Hospital, Sendai, Japan; Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (T.Ohkubo); The Faculty of Medical Science and Welfare, Tohoku Bunka Gakuen University, Sendai, Japan (M.H.); Department of Pharmacy, Sendai Open Hospital, Sendai, Japan (T.Hashimoto); Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, Studies Coordinating Centre, University of Leuven, Leuven, Belgium (A.Hara, K.A); Early Development and Pathologies, Center for Interdisciplinary Research in Biology, Collège de France, Paris, France (T.Hirose); Department of Career Design, Sendai Seiyo Gakuin College, Sendai, Japan (A.Hosokawa); Department of Social Welfare, Tohoku Fukushi University, Sendai, Japan (K.T.); and Department of Medicine, Ohasama Hospital, Iwate, Japan (H.H.). *These authors contributed equally to this work. The online-only Data Supplement is available with this article at Correspondence to Takayoshi Ohkubo, Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan. tohkubo@mail.tains.tohoku.ac.jp 4 American Heart Association, Inc. Hypertension is available at DOI:.6/HYPERTENSIONAHA..89

2 4 Hypertension June 4 Table. Participants Characteristics MMSE Score at Follow-Up Characteristics 4 (n=49) <4 (n=46) P Value Sex-, Age-, and Follow-Up Duration-Adjusted P Value Men, n (%) (6) 4 (5).. Age, y 6.± ±4...9 Body mass index, kg/m.8±.8.9±..7.6 Smoking, n (%) 46 () 8 (7)..7 Drinking, n (%) 8 (9) 9 (4).9.6 Diabetes mellitus, n (%) 49 () (4)..6 Hypercholesterolemia, n (%) 79 (4) 9 (4).9. Past history of CVD, n (%) (7) ()..6 Antihypertensive medication, n (%) () (46)..6 Years of education < y, n (%)* 6/49 (7) 6/4 (86).7.4 MMSE score at baseline <7, n (%) 8 (8) 6 (57) <. <. Decline in MMSE score, points.±. 4.5±. <. <. Follow-up duration, y 7.5±.5 8.6±4..4. The number of follow-up visits, times.7±.8.7±.7.5. Home BP, mm Hg Systolic.9±4.6.±..5.4 Diastolic 75.7± ±9.5.. Pulse pressure 48.±9. 5.8± SD of systolic BP 8.6±.5 9.8±.5.. SD of diastolic BP 5.6±.8.±.8.. Conventional BP (n=48), mm Hg Systolic 9.± ±8... Diastolic 78.4±.8 79.±..6.6 Pulse pressure 6.6± ± Men were only adjusted by age and follow-up duration. Age was only adjusted by sex and follow-up duration. Follow-up duration was only adjusted by sex and age. BP indicates blood pressure; CVD, cardiovascular disease; and MMSE, Mini-Mental State Examination. *Educational status was collected for 46 (95.%) participants by interview. provided. 7 Thus, it can be hypothesized that home BP can better predict future cognitive decline than conventional BP. One of the clinically significant aspects of home BP measurements is produced by the multiple BP measurements. 6 These multiple home BP measurements can also produce day-to-day BP variability that is calculated from the SD of home BP. Our previous studies demonstrated that high day-to-day BP variability was associated with an increased risk of cardiovascular mortality, independent of home BP values, and other risk factors. 8,9 However, no studies have investigated the associations of day-to-day BP variability with cognitive impairment. The objectives of this prospective study were to examine and to confirm the stronger predictive power of home BP values for cognitive decline than conventional BP and to compare the predictive power of the averaged home BP and the day-to-day home BP variability for cognitive decline. Methods Design This report was part of the Ohasama study, a community-based BP measurement project ongoing since 987. Socioeconomic and demographic characteristics of this region and details of the study have been described previously. 5,6 Study Population Of the remaining 4 eligible individuals, 46 participated in the baseline examination, and 96 gave informed consent for follow-up analyses. Of these, the total number of participants included in the present analyses was 485 without cognitive decline (defined as a baseline Mini-Mental State Examination [MMSE] score, <4)., A comparison of the characteristics of the excluded participants and the 485 participants who remained in this follow-up study is shown in Table S in the online-only Data Supplement. BP Measurement Participants were asked to measure BP and heart rate once every morning for a period of 4 weeks using an oscillometric device (HEM 7C or 747IC-N; Omron Healthcare Co Ltd, Kyoto, Japan)., The value and variability of home BP were calculated as the average and withinparticipant SD of the measurements, respectively. 8 Conventional BP was measured twice consecutively by well-trained physicians or nurses in the sitting position, after a minimum -minute interval of rest using an automatic device (HEM 97; Omron Healthcare Co Ltd). The mean of the readings was defined as the conventional BP. The details of BP measurement are described in the online-only Data Supplement. Assessment of Cognitive Function Outcome Cognitive decline was defined as an MMSE score of <4 at follow-up., The outcome of this study was defined as new onset of cognitive decline at follow-up examination. The details of MMSE measurements are described in the online-only Data Supplement.

3 Matsumoto et al Day-to-Day BP Variability and Cognitive Decline 5 Physical and Biochemical Examinations The methods for physical and biochemical examinations in the present study are described in the online-only Data Supplement. Statistical Analysis The analyses of the data in the present study are described in the online-only Data Supplement. Because several previous studies reported that treatment with antihypertensive medication could affect the predictive power of BPs for prognosis, 4,5 participants were divided into groups according to the use of antihypertensive medication. SAS version 9. software (SAS Institute Inc, Cary, NC) was used for statistical analysis. Results Participants and Characteristics The participants characteristics according to cognitive function at follow-up are shown in Table. The proportion of men, history of cardiovascular disease, low level of education, duration of follow-up, prevalence of a baseline MMSE score <7, home BP values, and SDs of home BP were significantly higher in participants with cognitive decline than in those without cognitive decline (Table ). Multiple Logistic Regression Analysis After a median follow-up of 7.8 years, 46 (9.5%) participants showed cognitive decline. The risk for cognitive decline was significantly increased across the tertiles of home systolic BP values (trend P=.4) and those of SD of home systolic BP (trend P=.46) after adjustments for possible confounding factors (Figure ). There were no significant associations between tertiles of conventional BP values and cognitive decline (odds ratio [95% confidence intervals] per tertile:. [],.4 [ ], and.5 [ ]; P.9 for systolic BP, and. [],.4 [.46.8], and.7 [.75.96]; P. for diastolic BP). Next, home or conventional systolic BP values and SDs of home systolic BP were analyzed as continuous variables (Figure S). Each -SD increase in the home systolic BP value showed a significant association with cognitive decline (odds ratio,.48; P=.). However, the conventional systolic BP value was not significantly associated with cognitive decline (P=.). Each -SD increase in SD of home systolic BP was significantly associated with cognitive decline, after including the averaged levels of home systolic BP in the same model (odds ratio,.5; P=.). Then, a positive association between the home systolic BP value and cognitive decline remained although it was weakened to a nonsignificant level (odds ratio [95% confidence interval],. [.9.88]; P=.). Stratified analyses according to the use of antihypertensive medication were then performed (Figure S). A high home systolic BP value and a high conventional BP value were significantly associated with cognitive decline only in participants on no antihypertensive treatment (P for interaction,. and., respectively) although the odds ratio per -SD increase in the conventional systolic BP value was lower than that of the home systolic BP value (.77 [.8.89] versus.8 [ ]; P.; Figure S). No significant interaction between the SD of home systolic BP and antihypertensive medication on cognitive decline was Odds ratios (95% C.I.) Odds ratios (95% C.I.) < >9.5 Home systolic BP value, mmhg Trend P =.46.4 ( ) Trend P =.4.4 (.78-5.).67 (.4-6.8)*.7 ( )* < >9.6 SD of home systolic BP, mmhg observed (P for interaction,.6; Figure S). The patients characteristics according to use of antihypertensive drugs are shown in Table S. Among the 4 on and the 5 not on antihypertensive treatment, 5 (5.%) and 7 (48.%), respectively, had home BPs 5/85 mm Hg. When the 8 untreated normotensives (home BPs, <5/85 mm Hg) were used as the erence, untreated hypertensives (home BPs, 5/85 mm Hg) and treated hypertensives had significantly higher risks for cognitive decline (Table S). When we divided the 485 study participants into 4 groups according to the medians of the home systolic BP values (4.7 mm Hg) and of the SD of the home systolic BP (8.55 mm Hg), the group with a higher SD of the home systolic BP ( 4.7 mm Hg) with a higher home systolic BP value ( 8.55 mm Hg) had the greatest risk for cognitive decline (Figure ). When all of the analyses were repeated using the diastolic BP value, similar trends, although not significant, were observed (Figure ; Figures S and S). Similar results were obtained when home BP values were defined as the mean of measurements obtained from the initial days (Table ). When cognitive decline was defined as MMSE scores of < or <5, similar tendencies were also observed (Tables S and S4). Home BP values (or initial days home BP) and conventional BP values were used in the same model. In participants on no antihypertensive treatment, only home BP values were significantly associated with cognitive decline (Tables S5 and S6). For the sensitivity analyses, further adjustments were made for home pulse pressure, body mass index, total cholesterol levels, smoking status, drinking status, diabetes mellitus, the < >79. Home diastolic BP value, mmhg Trend P =.9. ( ) Trend P =..89 (.7-4.9).7 ( ).7 ( ) < >6. SD of home diastolic BP, mmhg Figure. Odds ratios (95% confidence intervals [CI]) for cognitive decline among the tertiles of home blood pressure (BP) values (top) and the tertiles of the SD of the home BPs (bottom), after adjusting for sex, age, history of cardiovascular disease, low level of education, baseline Mini-Mental State Examination (MMSE) score <7, and follow-up duration. In the analysis of the SDs of the home BP measurements, further adjustments were made for the home systolic BP value. Cognitive decline was defined as MMSE score <4 at follow-up. P<.5 vs erence ().

4 6 Hypertension June 4 Odds ratios (95% C.I.) /85.79 ( ) 4.7 <4.7 Home systolic BP, mmhg /58 6.4* / * (.-9.4) ( ) 5/ <8.6 SD of home systolic BP, mmhg Figure. Odds ratios (95% confidence intervals [CI]) for cognitive decline associated with the combination of home systolic blood pressure (BP) value and the SD of the home systolic BP, after adjusting for sex, age, history of cardiovascular disease, low level of education, baseline Mini-Mental State Examination (MMSE) score <7, and follow-up duration. The incidence/number of subjects in each group is shown on each bar. A higher home systolic BP value is defined as 4.7 mm Hg (dichotomized at upper quartiles). A higher SD of the home BP is defined as 8.6 mm Hg (dichotomized at upper quartiles). Cognitive decline is defined as an MMSE score <4 at follow-up. *P<.5 vs erence (). use of antihypertensive drugs, and the number of follow-up visits. Even after applying these adjustments, the significant association of the SD of the home systolic BP with cognitive decline was unchanged (odds ratio,.47; P.), whereas the significant association of the home systolic BP with cognitive decline remained only in participants not on antihypertensive treatment (odds ratio,.6; P.). Discussion There are key novel findings of the present study. First, in line with the previous studies demonstrating the clear association of home BP with cardiovascular disease 6 or target organ damage, 5 the home BP values were more strongly associated with cognitive decline than conventional BP values. Second, this is the first study demonstrating a significant association between day-to-day BP variability, defined as the SD of home measurements and cognitive decline independent of home systolic BP. Previous longitudinal studies reported significant associations between elevated conventional BP and an increased risk for cognitive decline. However, home BP values were more strongly associated with cognitive decline than conventional BP values. Consistent with the results of previous studies, 4,5 the association of BP values with cognitive decline was strengthened for participants on no antihypertensive treatment. We previously reported that the predictive value of the initial days home BP for stroke was greater than that of office BP readings. 6 Consistent with this, the results based on the initial days home BP (Table ) suggest that the home BP values might more strongly predict future cognitive decline than conventional BP, regardless of the number of measurements. The stronger association between the home BP value and cognitive decline than between the conventional BP value and cognitive decline can be explained by the fact that out-of-office BP measurements provide more reproducible information on BP, 6 eliminate the white-coat effect, 4 have more prognostic significance, 6 and are more indicative of target organ damage than conventional BP measurements. 5 Recent epidemiological studies have reported the strong prognostic value of home BP when compared with conventional BP. 9,7,8 The conventional BP values were higher than the home BP values, suggesting the possibility that conventional BP included the white-coat effect in the present study (Table ). This is consistent with previous studies. 8 However, the relationships of the measurements with cognitive decline do not resolve the issue of day-to-day BP variability in terms of white-coat hypertension because the conventional BP measurements cannot provide day-to-day BP variability. Table. The Associations of the Initial -Day Home and Conventional BPs With Cognitive Decline Independent Variables (Per SD Increase) Subgroups Odds Ratio (95% Confidence Interval) for Cognitive Decline P Value Interaction for P Value (BP Antihypertensive Treatment) Home systolic BP All participants.47 (.4.7). Treated.9 (.5.7).8. Untreated. (.7.54).4 Home diastolic BP All participants.55 (..7). Treated.4 (.59.85).9. Untreated.95 (.6 5.6).4 Conventional systolic BP All participants. (.88.67). Treated.8 (.5.4).4.9 Untreated.75 (.7.84). Conventional diastolic BP All participants.9 (.78.5).6 Treated.9 (.55.58).8.5 Untreated.8 (.79.8). Home blood pressure (BP) values were based on measurements obtained from initial days. We analyzed in 49 participants who measured morning home BP recordings. Overall, and 5 participants had cognitive decline among subgroups treated (n=55) and untreated (n=6) with antihypertensive medication, respectively. Odds ratios were adjusted for sex, age, history of cardiovascular disease, low level of education, baseline Mini-Mental State Examination score <7, and follow-up duration. In the analysis of the SD of the home systolic BP measurement, we further adjusted for home systolic BP value.

5 Matsumoto et al Day-to-Day BP Variability and Cognitive Decline 7 The present study demonstrated for the first time that day-to-day BP variability may predict cognitive decline in a general population. The visit-to-visit variability in office BPs was recently reported to be associated with impaired cognitive function. 9 This report supports the present results. However, their study was conducted in a special patient population at high risk of cardiovascular disease, and the visit-to-visit BP variability was calculated from multiple office BPs measured every months during a relatively short-term follow-up of. years. 9 Furthermore, it is difficult to evaluate visit-to-visit BP variability in normotensives or untreated hypertensives who do not regularly go to a hospital. One cross-sectional study demonstrated the association of elevated short-term BP variability with cognitive impairment in patients aged 6 years with stable treatments for various chronic diseases. It has been reported that day-to-day BP variability and short-term BP variability can be related to autonomic dysfunction, carotid intima-media thickness, and cardiovascular mortality. 8, Orthostatic hypotension, which is one of the symptoms of autonomic dysfunction, can cause cerebral ischemia and has been reported to be associated with dementia. 4 Several studies have reported that atherosclerosis can also be a factor related to cognitive decline or dementia. 5,6 From these previous studies,,,5,6 the association of day-to-day BP variability with cognitive decline may be mediated partly by autonomic dysfunction and arterial stiffness although home pulse pressure was not associated with cognitive decline. Previously, we demonstrated the significant association of high day-to-day BP variability with the risk of cardiovascular mortality in a general population. 8 Theore, measuring not only the BP value itself but also day-to-day BP variability may provide important information for detecting early stages of dementia and cardiovascular disease. This study had several limitations. First, study participants included predominantly middle-aged and elderly women and were selected only from volunteers who could participate in health check-ups during the daytime. Furthermore, the numbers of participants and cognitive decline events were small. These might, to some extent, limit the external validity of the findings. Second, the follow-up participants (n=485) were significantly younger, had lower home systolic BP values, included a higher proportion of participants on no antihypertensive medication, and had a higher level of education and lower mortality after the last examination than the excluded participants (n=67; Table S). Thus, participants in the follow-up examination of the present study represent a relatively healthy group. This might have led to an underestimation of the true relationships between BP values or day-to-day BP variability and cognitive decline. Third, marked differences exist in the epidemiology of dementia between Japan and the United States or European countries. However, in relation to the significant prognostic power of day-to-day variability, similar findings to our previous study were obtained in the Finn-Home study, in which the subjects were Finnish. 7 Thus, it is possible that the association of day-to-day BP variability with cognitive decline in Japanese may also not differ from that in whites. Fourth, data on depression status, using the Sheehan Disability Scale, were collected in only study participants, making it impossible to take into account the effect of depression. Finally, conventional BP was defined as measurements on a single occasion in the present study. The American Heart Association and other guidelines,8 recommend taking BP assessments on separate occasions to diagnose a patient with hypertension. Furthermore, it has been reported that future cognitive decline is strongly predicted by office BP measured on multiple occasions. Thus, the predictive power of conventional BP for cognitive decline would be enhanced by multiple measurements. Further studies based on multiple BP measurements in an office are needed to elucidate the stronger predictive power of home BP for cognitive decline when compared with that of BP measured in an office. Then, automated office BP measurement, which is recommended by the Canadian guideline, may be useful to assess multiple BP values in an office. 9 Perspective The present study provides the first prospective evidence that, in a general population, home BP values and day-to-day home BP variability may predict cognitive decline. Home BP measurement has already been recommended for management of hypertension by guidelines,,6 including the European Society of Hypertension and the European Society of Cardiology guideline. 8 In addition, the present study suggests that BP values and day-to-day BP variability derived from self-measurement at home may also be a simple method of providing useful clinical information for assessing cognitive decline. Acknowledgments We are grateful to the residents of the town of Ohasama, all related investigators and study staff, and staff members of the Ohasama Town Government, Ohasama Hospital, and Iwate Pectural Stroke Registry for their valuable support for this project. A. Matsumoto and M. Satoh wrote the first draft of this article. All authors conducted the Ohasama Study and commented on the article. Sources of Funding This work was supported by grants for Scientific Research (496, 97, 4596, 4984, 4596, , 5465, 5468, and 58656) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; Grants-in-Aid for Japan Society for the Promotion of Science fellows (5.98 and ); a Health Labor Sciences Research Grant (H-Junkankitou [Seishuu]-Ippan-5) from the Ministry of Health, Labor, and Welfare, Japan; the Japan Arteriosclerosis Prevention Fund; a grant from the Daiwa Securities Health Foundation; and Research Funding for Longevity Sciences ( ) from the National Center for Geriatrics and Gerontology. None. Disclosures References. Elias MF, Goodell AL, Dore GA. Hypertension and cognitive functioning: a perspective in historical context. Hypertension. ;6: Elias MF, Robbins MA, Elias PK, Streeten DH. A longitudinal study of blood pressure in relation to performance on the Wechsler Adult Intelligence Scale. Health Psychol. 998;7: Elias MF, Wolf PA, D Agostino RB, Cobb J, White LR. Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. Am J Epidemiol. 99;8: Parati G, Stergiou GS, Asmar R, et al.; ESH Working Group on Blood Pressure Monitoring. European Society of Hypertension guidelines for

6 8 Hypertension June 4 blood pressure monitoring at home: a summary report of the Second International Consensus Conference on Home Blood Pressure Monitoring. J Hypertens. 8;6: Hara A, Ohkubo T, Kikuya M, et al. Detection of carotid atherosclerosis in individuals with masked hypertension and white-coat hypertension by self-measured blood pressure at home: the Ohasama study. J Hypertens. 7;5: Ohkubo T, Asayama K, Kikuya M, Metoki H, Hoshi H, Hashimoto J, Totsune K, Satoh H, Imai Y; Ohasama Study. How many times should blood pressure be measured at home for better prediction of stroke risk? Ten-year follow-up results from the Ohasama study. J Hypertens. 4;: Asayama K, Ohkubo T, Metoki H, Obara T, Inoue R, Kikuya M, Thijs L, Staessen JA, Imai Y; Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP). Cardiovascular outcomes in the first trial of antihypertensive therapy guided by self-measured home blood pressure. Hypertens Res. ;5:. 8. Kikuya M, Ohkubo T, Metoki H, Asayama K, Hara A, Obara T, Inoue R, Hoshi H, Hashimoto J, Totsune K, Satoh H, Imai Y. Day-by-day variability of blood pressure and heart rate at home as a novel predictor of prognosis: the Ohasama study. Hypertension. 8;5: Asayama K, Kikuya M, Schutte R, Thijs L, Hosaka M, Satoh M, Hara A, Obara T, Inoue R, Metoki H, Hirose T, Ohkubo T, Staessen JA, Imai Y. Home blood pressure variability as cardiovascular risk factor in the population of Ohasama. Hypertension. ;6: Mori E, Mitani Y, Yamadori A. Usefulness of a Japanese version of the Mini-Mental State Test in neurological patients. Jpn J Neuropsychol. 985;:8 9.. Folstein M, Anthony JC, Parhad I, Duffy B, Gruenberg EM. The meaning of cognitive impairment in the elderly. J Am Geriatr Soc. 985;:8 5.. Ogihara T, Kikuchi K, Matsuoka H, et al.; Japanese Society of Hypertension Committee. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 9). Hypertens Res. 9;: 7.. Imai Y, Satoh H, Nagai K, Sakuma M, Sakuma H, Minami N, Munakata M, Hashimoto J, Yamagishi T, Watanabe N, Yabe T, Nishiyama A, Nakatsuka H, Koyama H, Abe K. Characteristics of a community-based distribution of home blood pressure in Ohasama in northern Japan. J Hypertens. 99;: Korf ES, White LR, Scheltens P, Launer LJ. Midlife blood pressure and the risk of hippocampal atrophy: the Honolulu Asia Aging Study. Hypertension. 4;44: den Heijer T, Launer LJ, Prins ND, van Dijk EJ, Vermeer SE, Hofman A, Koudstaal PJ, Breteler MM. Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe. Neurology. 5;64: Imai Y, Kario K, Shimada K, Kawano Y, Hasebe N, Matsuura H, Tsuchihashi T, Ohkubo T, Kuwajima I, Miyakawa M; Japanese Society of Hypertension Committee for Guidelines for Self-monitoring of Blood Pressure at Home. The Japanese Society of Hypertension Guidelines for Self-monitoring of Blood Pressure at Home (Second Edition). Hypertens Res. ;5: Hänninen MR, Niiranen TJ, Puukka PJ, Johansson J, Jula AM. Prognostic significance of masked and white-coat hypertension in the general population: the Finn-Home Study. J Hypertens. ;: Niiranen TJ, Asayama K, Thijs L, Johansson JK, Ohkubo T, Kikuya M, Boggia J, Hozawa A, Sandoya E, Stergiou GS, Tsuji I, Jula AM, Imai Y, Staessen JA; International Database of Home Blood Pressure in Relation to Cardiovascular Outcome Investigators. Outcome-driven thresholds for home blood pressure measurement: international database of home blood pressure in relation to cardiovascular outcome. Hypertension. ;6: Sabayan B, Wijsman LW, Foster-Dingley JC, Stott DJ, Ford I, Buckley BM, Sattar N, Jukema JW, van Osch MJ, van der Grond J, van Buchem MA, Westendorp RG, de Craen AJ, Mooijaart SP. Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study. BMJ. ;47:f46.. Sakakura K, Ishikawa J, Okuno M, Shimada K, Kario K. Exaggerated ambulatory blood pressure variability is associated with cognitive dysfunction in the very elderly and quality of life in the younger elderly. Am J Hypertens. 7;: Zhang Y, Agnoletti D, Blacher J, Safar ME. Blood pressure variability in relation to autonomic nervous system dysregulation: the X-CELLENT study. Hypertens Res. ;5: Tatasciore A, Renda G, Zimarino M, Soccio M, Bilo G, Parati G, Schillaci G, De Caterina R. Awake systolic blood pressure variability correlates with target-organ damage in hypertensive subjects. Hypertension. 7;5:5.. Kikuya M, Hozawa A, Ohokubo T, Tsuji I, Michimata M, Matsubara M, Ota M, Nagai K, Araki T, Satoh H, Ito S, Hisamichi S, Imai Y. Prognostic significance of blood pressure and heart rate variabilities: the Ohasama study. Hypertension. ;6: Allan LM, Ballard CG, Allen J, Murray A, Davidson AW, McKeith IG, Kenny RA. Autonomic dysfunction in dementia. J Neurol Neurosurg Psychiatry. 7;78: Wendell CR, Zonderman AB, Metter EJ, Najjar SS, Waldstein SR. Carotid intimal medial thickness predicts cognitive decline among adults without clinical vascular disease. Stroke. 9;4: van Oijen M, de Jong FJ, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Atherosclerosis and risk for dementia. Ann Neurol. 7;6: Johansson JK, Niiranen TJ, Puukka PJ, Jula AM. Prognostic value of the variability in home-measured blood pressure and heart rate: the Finn-Home Study. Hypertension. ;59: Mancia G, Fagard R, Narkiewicz K, et al. ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. ;4: Myers MG, Godwin M. Automated office blood pressure. Can J Cardiol. ;8:4 46. Novelty and Significance What Is New? This is the first prospective study to demonstrate that higher home blood pressure (BP) values and higher SD of home systolic BP were significantly associated with an increased risk for cognitive decline in a general population. What Is Relevant? Home BP values and day-to-day home BP variability can be important predictors for cognitive decline in a general population. Summary A higher home BP value with a higher SD of home BP was associated with future cognitive decline. Thus, measuring not only the home BP value but also day-to-day BP variability may provide important information for detecting early stages of cognitive decline.