Cover Page The handle http://hdl.handle.net/1887/48285

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Cover Page

The handle http://hdl.handle.net/1887/48285 holds various files of this Leiden University dissertation

Author: Moonen, J.E.F.

Title: Blood pressure and neuropsychiatric symptoms in old age

Issue Date: 2017-04-11

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Blood pressure

and neuropsychiatric symptoms in old age

Justine Emilie Frederiek Moonen

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Blood pressure and neuropsychiatric symptoms in old age

Justine E.F. Moonen

Thesis, Leiden University Medical Center, the Netherlands, 2017

Cover: Sculpture ‘A different look inside the head’ by Hanne de Charro, sculptor Photography by Jan van Rijthoven

Lay out: Iliana Boshoven-Gkini | AgileColor.com Printed by: GVO drukkers & vormgevers B.V. | GVO.nl ISBN: 978-94-6332-122-8

The research project presented in this thesis was funded by a grant from Program Priority Medicines for the Elderly, the Netherlands Organization for Health Research and Development (ZonMW), project number: 113101003.

Printing of this thesis was financially supported by Alzheimer Nederland and Chipsoft.

© J.E.F. Moonen 2017

No part of this thesis may be reproduced or distributed in any form or by any means without prior

permission of the author or, when appropriate, the copyright owning journals.

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Blood pressure

and neuropsychiatric symptoms in old age

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus Prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op dinsdag 11 april 2017

klokke 15.00 uur

door

Justine Emilie Frederiek Moonen geboren te Leiden

in 1983

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Promotor

Prof. dr. R.C. van der Mast

Co-promotores

Dr. W. de Ruijter en Dr. A.J.M. de Craen

^†

Promotiecommissie

Prof. dr. W.P. Achterberg

Dr. M. Muller, Vrije Universiteit Medisch Centrum (VUmc) Prof. dr. M.L. Stek, Vumc

Prof. dr. W.A. van Gool, Amsterdam Medisch Centrum (AMC)

Financial support by the Dutch Heart Foundation for the publication of this thesis is

gratefully acknowledged

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To my father

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General introduction | 11

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Figure 1. Flow Diagram NESDO study population IDS-SR= Inventory of Depressive Symptoms-Self Report

Presence of depressive disorder (n=378)

Current (last month) depressive disorder (n=303)

Depressive disorder >1 month ago (n=75)

Missing data on blood pressure, Apathy Scale and/or IDS-SR (sub) scale scores (n=33)

Study sample (n=270)

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-101

IDS-SR motivation IDS-SR mood IDS-SR somatic

Apathy Scale Beta (95% CI)

Systolic Blood Pressure p= 0.55 p= 0.03 p= 0.17

p= 0.045 1.5-101 Beta (95% CI)

Diastolic Blood Pressure p= 0.71 p= 0.32 p= 0.06

p= 0.03 1.5-101 Beta (95% CI)

Mean Arterial Pressure p= 0.91 p= 0.08 p= 0.07

p= 0.02 1.5

Fig u re 2 . C h an ge in IDS -S R su b sc al e an d Apa th y S ca le s co re fo r i n cr e as e in blo o d press u re m e as u re s. ( n =2 70 ) SBP =s ys to lic b lo o d p re ss u re , DBP =d ias to lic b lo o d p re ss u re , MA P= Me an A rt eri al Pre ss u re , CI=Co n fi d en ce In te rval . IDS -S R = In ve n to ry o f De p re ss ive S ymp to ms -S el f R e p o rt . Un stan d ard iz ed Bet a’ s ( 95% CI) w ere c al cu late d p er 10 mmH g i n cre as e i n b lo o d p re ss u re me as u re s ad ju ste d fo r ag e , g en d e r, ma ri tal s tat u s, e d u cati o n , u se o f a lc o h o l, an ti h yp er te n si ve an d p syc h o tr o p ic me d ic ati o n , MMS E, c h ro n ic p ai n g rad e, n u mb er o f c h ro n ic d is eas e s. A d d iti o n al ly: eac h IDS -S R s u b sc al e w as ad ju st ed fo r t h e o th er t w o s u b sc al e s an d t h e A p ath y s cal e w as ad ju ste d fo r t h e IDS -S R mo o d an d IDS -S R s o mati c s u b sc al e.

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-2.0-1.5-1.0-0.50.00.51.01.5

S B P D B P M A P

A p a th y S c a le S c o re P f o r in te ra c ti o n < 0 .0 0 1 < 0 .0 0 1 < 0 .0 0 1

B e ta ( 9 5 % C I)

-1.0-0.50.00.51.0

0 .9 0 0 .4 4 0 .7 6

G D S -1 5 P f o r in te ra c ti o n B e ta ( 9 5 % C I)

n=209 persons with a lower functional ability according to GARS >22 n=220 persons with a higher functional ability according to GARS

Fig u re 1 . C h an ge in A p ath y S ca le o r G er ia tr ic Dep re ss io n S ca le ( G DS )- 15 s co re pe r 1 0 m mH g i n cr e as e in blo o d press u re m ea su re s, s tr ati fi e d o n le ve l o f fu n cti o n al ab ili ty

Analyses were adjusted for gender, age, education, current smoking, use of alcohol, history of cardiovascular disease, number of chronic diseases, use of psychotropic medication, use of beta blockers and MMSE. SBP= systolic blood pressure, DBP= diastolic blood pressure, MAP= mean arterial pressure, GARS= Groningen Activity Restriction of life Scale, range GARS score: 18-72, median GARS score=22.

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52 | Chapter 3 Lower blood pressure and apathy | 53

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Figure 1. Receiver Operating Characteristic (ROC) curve for GDS-3A compared to the Apathy

Scale in the DANTE Study and PROMODE Study

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Persons assessed for eligibility

Not meeting inclusion criteria Cardiac arrhythmias History of stroke Angina pectoris

Randomized to discontinuation of antihypertensive treatment (110 with baseline MRI)

Received intervention as randomized Did not receive intervention as randomized

1 Randomized to continuation of antihypertensive treatment (105 with baseline MRI) Received intervention as randomized

Ineligible MMSE score >27 MMSE score <21

Not meeting other inclusion criteria Declined to participate Other reasons

Baseline measurements (236 with baseline MRI)

No follow-up measurements died

Withdrew consent Health reasons

Included in intention-to-treat analysis (105 with baseline MRI)

Included in intention-to-treat analysis (100 with baseline MRI)

Not included

Not meeting inclusion criteria Withdrew consent Health reasons MRI chance findings Infarcts Aneurysms

Normal-pressure hydrocephalus Meningioma

Cavernoma

Internal carotid artery occlusion

No follow-up measurements Died

Withdrew consent Health reasons Randomized

(220 with baseline MRI)

.

MMSE indicates Mini-Mental State Examination; MRI, magnetic resonance imaging.

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90 | Chapter 5 Discontinuation of ANtihypertensive Treatment in Elderly people | 91

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430 baseline measurements DANTE trial

179 randomised 221 no OH

10 missing data on OH

46 complete discontinuation 21 partial discontinuation 19 no discontinuation 10 restarted or additional 7 no change

2 missing data

199 persons with OH

20 not included

13 not meeting DANTE inclusion criteria 4 withdrew consent

3 for health reasons.

5 no follow-up measure 3 withdrew consent 1 for health reasons 1 missing data on OH at FU 7 no follow-up measurements

4 withdrew consent 3 for health reasons

5 not meeting inclusion criteria

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1 .0 1 .5 2 .0 2 .5

R e la ti v e ri s k (9 5 % C I) P

Favors continuationFavors discontinuation

In te n ti o n -t o -t re a t C o m p le te o r p a rt ia l C o m p le te o n ly

Crude

D is c o n ti n u a ti o n C o n ti n u a ti o n

R e c o v e ry fr o m o rt h o s ta ti c h y p o te n s io n

43/86(50%)29/76(38%)

no./totalno.(%) 1.31(0.92to1.87)0.13

no./totalno.(%) 37/67(55%)29/76(38%)0.041.45(1.01to2.07)Crude Adjusted*1.37(0.95to1.97)0.09

0 .5

28/46(61%)29/76(38%)0.011.60(1.10to2.31)Crude Adjusted*1.59(1.08to2.33)0.02 Adjusted**1.42(0.98to2.04)0.06 Adjusted**1.72(1.15to2.57)0.01

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108 | Chapter 6 Discontinuation of antihypertensive treatment and orthostatic hypotension | 109

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Figure adapted from JAMA Intern Med. 2015;175:586-58745

Midlife high blood pressure

Cognitive and psychological dysfunction Cerebral hypoperfusion

Late-life low blood pressure

Cerebrovascular disease

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Nederlandse samenvatting | 165

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List of publications | 169

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Dankwoord | 173

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