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1 중년과 노년기의 혈압이 뇌에 미치는 연합 효과 AGES-Reykjavik 연구 Joint effect of mid-and late-life blood pressure on the brain The AGES-Reykjavik Study Majon Muller, MD, PhD Sigurdur Sigurdsson, MSc Olafur Kjartansson, MD Thor Aspelund, PhD Oscar L. Lopez, MD Palmi V. Jonnson, MD Tamara B. Harris, MD Mark van Buchem, MD, PhD Vilmundur Gudnason, MD, PhD Lenore J. Launer, PhD For the Age, Gene/ Environment Susceptibility- Reykjavik Study Investigators 목적: 고혈압의 병력이 있는 사람에서 노년기의 낮은 혈압 (blood pressure, BP)은 뇌 병리와 관계가 있을 것이라고 가정하였 다. 방법: Age, Gene/Environment Susceptibility (AGES)-Reykjavik 연구의 일환으로 치매가 없는 중년 (평균 연령 50±6세)과 노 년 (평균 연령 76±5세)의 참가자 4,057명에서 혈관 검사, 인지기능 검사를 시행하고 MRI를 통해 뇌의 구조를 조사하였다. 결과: 노년의 혈압과 뇌의 관계는 중년의 고혈압 병력에 기반하여 평가하였다. 노년기의 높은 수축기와 이완기 혈압(diastolic BP, DBP)은 백질 병변과 뇌 미세출혈의 위험을 증가시키고 이것은 대부분 고혈압의 병력이 없던 중년의 참가자에서 발생하였 다. 이와 대조적으로 중년에 고혈압의 병력이 있는 참가자에서 노년기의 낮은 DBP는 전체 뇌 용적 및 회색질 용적의 감소와 관계가 있었다. 이러한 결과는 인지 수행 능력에 반영되었다. 중년에 고혈압이 있는 참가자에서 낮은 DBP는 낮은 기억 점수와 연관이 있었다. 결론: 이 대규모 인구기반 코호트에서 중년기 고혈압 병력 여부에 따라 노년기 혈압은 뇌 병리와 인지 기능에 서로 다른 영향 을 주었다. 고혈압의 병력은 노년기 혈압이 뇌의 구조와 기능에 미치는 영향을 이해하는 데 결정적이라는 것을 제시한다. Neurology 2014;82: (blood pressure, BP) , 6-8, ,11,12, , 16., 방 법 AGES-Reykjavik Study Gene/Environment Susceptibility (AGES) Reykjavik Study Reykjavik study. Reykjavik Study ( ) Icelandic Heart Association Reykjavik AGES-Reykjavik Study.. 20 표준 프로토콜 승인, 등록, 그리고 환자의 동의 AGES-Reykjavik Study Icelandic National Bioethics Committee (VSN ) Institutional Review Board of the US National Institute on Aging, NIH.. Neurology 한국어판 Vol. 8 No. 3 13

Launer, PhD For the Age, Gene/ Environment Susceptibility- Reykjavik Study Investigators 목적: 고혈압의 병력이 있는 사람에서 노년기의 낮은 혈압 (blood pressure, BP)은 뇌 병리와 관계가 있을 것이라고 가정하였 다.

2 뇌 MRI MRI 1.5 Signa Twinspeed Excite system (General Electric Medical Systems, Waukesha, WI) T1-, proton density-, T2 * -, T2-weighted fluid-attenuated inversion recovery (FLAIR). 21 (gray matter, GM), (white matter, WM), CSF, WM (WM lesion, WML) (ml) Montreal Neurological Institute AGES-Reykjavik Study-modified. 21,22 (total brain volume, TBV) GM, WM WML. (intracranial volume, ICV) TBV CSF, GM (GMV) WM (WMV) ICV (% ICV). WML WML ( ). (radiographers) T2 FLAIR. 4 mm.. : T2 *, T 인지기능 (1) California Verbal Learning Test, (2) Figure Comparison Test, Digit Symbol Substitution Test Stroop1 2, (3) CANTAB Spatial Working Memory test, Digits Backward test, Stroop3. Z. (interrater reliability) (Spearman correlation range ). 중년과 노년기의 혈압 Reykjavik AGES-Reykjavik Study Iceland World Health Organization European guidelines. (systolic BP, SBP) (diastolic BP, DBP) ( x : 15x22 cm) 2 mmhg. BP>140/90 mmhg. SBP DBP. SBP: 120, , >140 mmhg, DBP: 70, 71-80, >80 mmhg. (pulse pressure, PP) SBP DBP. 기타 변수들,. 20 /, ( )., (body mass index, BMI)(kg/m 2 ). 126 mg/dl. /.,, Rose Angina Questionnaire ECG /. ICD-10 : I50*, I11.0, I13.2, I97.13, I 분석 표본 AGES-Reykjavil Study 5, MRI ,614 (n=260). 24 (n=48), (n=227), (n=22). 4,057. AGES-Reykjavik,, TBV ( ). 자료 분석 14 Neurology 한국어판 Vol. 8 No. 3

(intracranial volume, ICV) TBV CSF, GM (GMV) WM (WMV) ICV (% ICV). WML WML ( ). (radiographers) T2 FLAIR. 4 mm.. : T2 *, T2. 23

3 .. Analysis of covariance (ANCOVA) SBP DBP (95% [confidence of interval, CI]). : 1 ; 2 ( ).,,. BP p. (,, ) ANCOVA ( X ). 결 과 DBP. (,, ) (BMI,,, ) (WML, 1, 2) (TBV, GMV, WMV).. SBP DBP( ) 연구 대상 인구의 특성 4,057 ( ) 50 (33-75) 76 (66-75) 59%. 34% (n=1,365) 6% (n= 251). (10 th -90 th percentile range) SBP DBP 142 mmhg ( ) 74 mmhg (62-86).,.,, MRI (table 1). DBP,,. DBP DBP (table 2). 중년의 고혈압과 노년기 뇌 구조 및 기능, (95% CI) Neurology 한국어판 Vol. 8 No. 3 15

. SBP DBP( ) 연구 대상 인구의 특성 4,057 ( ) 50 (33-75) 76 (66-75) 59%. 34% (n=1,365) 6% (n= 251).

4 WMLs 1.3 ( ), 1.2 ( ), 1.4 ( )., (% ICV) ; TBV, GMV WMV (95%CI) -0.5% ICV (-0.7; -0.2), -0.4% ICV (-0.6; -0.2), -0.2% ICV (-0.3; -0.1)., ;, (95% CI) (-0.085; 0.020) (-0.060; 0.026), (-0.082; ).. 뇌혈관 병변에 대한 중년 고혈압과 노년기 BP의 연합 관계 SBP WMLs,, (table 3). DBP WMLs (table 3). DBP.. table 3 ( ). 뇌 용적에 대한 중년 고혈압과 노년기 BP의 연합 관계 SBP DBP WMV. WMLs,, (table 4). DBP ( SBP) TBV GMV (table 4). DBP 70 mmhg) TBV GMV, (figure, A); TBV GM p ( X DBP) Neurology 한국어판 Vol. 8 No. 3

. 뇌혈관 병변에 대한 중년 고혈압과 노년기 BP의 연합 관계 SBP WMLs,, (table 3). DBP WMLs (table 3). DBP.. table 3 ( ).

5 Neurology 한국어판 Vol. 8 No. 3 17

6 18 Neurology 한국어판 Vol. 8 No. 3

7 . TBV GMV DBP DBP -0.59% ICV (-1.07; -0.11) -0.55% ICV (-0.96; -0.15). 인지기능에 대한 중년기와 노년기 BP의 연합 관계 SBP DBP, BP (figure, B for DBP). DBP DBP. DBP. DBP DBP (95% CI -0.24; -0.00). p ( X DBP) BP ( ). Neurology 한국어판 Vol. 8 No. 3 19

8 : (1) (n=260), (n=227), (2) 3,806, (3) 65 (n=27) (4) (Mini Mental State Examination) <24 (n=303) ( BP ). 고 찰, 8-10 BP. 6 BP., SBP DBP.,, DBP TBV GM. ; DBP. BP. SBP DBP WMLs,. 4, BP. BP. DBP,, GMV. BP BP. 11,18,29,30 BP. 16,31. DBP., BP., 14,15,. 15,16,23 (table 2 ), BP., DBP, BP. ( ), BP. SBP, SBP. 33. BP. BP, BP.., -.. Reykjavik Study Reykjavik Study (34% vs 50%).., 50% 20 Neurology 한국어판 Vol. 8 No. 3

BP BP. 11,18,29,30 BP. 16,31. DBP., BP., 14,15,. 15,16,23 (table 2 ), BP., DBP, BP. ( ), BP. SBP, SBP.

9 AUTHOR CONTRIBUTIONS Dr. Muller: analysis and interpretation, writing manuscript, critical revision of the manuscript for important intellectual content. Dr. Sigurdsson: acquisition of data, critical revision of the manuscript for important intellectual content. Dr. Kjartansson: critical revision of the manuscript for important intellectual content. Dr. Aspelund: acquisition of data, critical revision of the manuscript for important intellectual content. Dr. Lopez: critical revision of the manuscript for important intellectual content. Dr. Jonnson: acquisition of data, critical revision of the manuscript for important intellectual content. Dr. Harris: study concept and design, critical revision of the manuscript for important intellectual content. Prof. van Buchem: critical revision of the manuscript for important intellectual content. Dr. Gudnason: study concept and design, critical revision of the manuscript for important intellectual content Dr. Launer: study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content, study supervision. STUDY FUNDING Supported by a grant from the NIH (N01-AG ), National Institute on Aging Intramural Research Program, the Hjartavernd (the Icelandic Heart Association), the Althingi (the Icelandic Parliament), and Alzheimer Nederland (M.M.; WE ). DISCLOSURE The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. Received July 19, Accepted in final form March 18, REFERENCES 1. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358: Law MR, Morris JK, Wald NJ. 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Dr. Jonnson: acquisition of data, critical revision of the manuscript for important intellectual content. Dr.

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Progression of cerebral white matter hyperintensities on MRI is related to diastolic blood pressure. Neurology 1998;51:319 320. 26. Poels MM, Vernooij MW, Ikram MA, et al.

저작자표시 - 비영리 - 변경금지 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할

저작자표시 - 비영리 - 변경금지 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할수없습니다. 변경금지. 귀하는이저작물을개작, 변형또는가공할수없습니다. 귀하는, 이저작물의재이용이나배포의경우,