Publications by authors named "Anne Suzanne Bertens"

9 Publications

  • Page 1 of 1

Lower Blood Pressure, Small-Vessel Disease, and Apathy in Older Persons With Mild Cognitive Deficits.

J Am Geriatr Soc 2020 08 30;68(8):1811-1817. Epub 2020 Apr 30.

Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.

Background: In older persons, both high and low blood pressure (BP) levels are associated with symptoms of apathy. Population characteristics, such as burden of cerebral small-vessel disease (CSVD), may underlie these apparently contradictory findings. We aimed to explore, in older persons, whether the burden of CSVD affects the association between BP and apathy.

Design: Cross-sectional study.

Setting: Primary care setting, the Netherlands.

Participants: Community-dwelling older persons (mean age = 80.7 years; SD = 4.1 years) with mild cognitive deficits and using antihypertensive treatment, participating in the baseline measurement of the magnetic resonance imaging substudy (n = 210) of the Discontinuation of Antihypertensive Treatment in the Elderly Study Leiden.

Measurements: During home visits, BP was measured in a standardized way and apathy was assessed with the Apathy Scale (range = 0-42). Stratified linear regression analyses were performed according to the burden of CSVD. A higher burden of CSVD was defined as 2 or more points on a compound CSVD score (range = 0-3 points), defined as presence of white matter hyperintensities (greater than median), any lacunar infarct, and/or two or more microbleeds.

Results: In the entire population, those with a lower systolic and those with a lower diastolic BP had more symptoms of apathy (β = -.35 [P = .01] and β = -.66 [P = .02], respectively). In older persons with a higher burden of CSVD (n = 50 [24%]), both lower systolic BP (β = -.64, P = .02) and lower diastolic BP (β = -1.6, P = .01) were associated with more symptoms of apathy, whereas no significant association was found between BP and symptoms of apathy in older persons with a lower burden of CSVD (n = 160).

Conclusions: Particularly in older persons with a higher burden of CSVD, lower BP was associated with more symptoms of apathy. Adequate BP levels for optimal psychological functioning may vary across older populations with a different burden of CSVD. J Am Geriatr Soc 68:1811-1817, 2020.
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August 2020

Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.

Neurology 2020 01 11;94(3):e267-e281. Epub 2019 Dec 11.

From Neuroscience Research Australia (R.P., K.J.A.); University of New South Wales (R.P., C.A., H.B., J.C., P.S.S., K.J.A.), Sydney, Australia; Johns Hopkins University (S.Y., M.C.C.), Baltimore, MD; The George Institute for Global Health (C.A., J.C.), Sydney, Australia; The George Institute China at Peking University Health Sciences Center (C.A.), Beijing, China; Icahn School of Medicine at Mount Sinai (S.A.), New York, NY; Center for Life Course Health Research/Geriatrics (R.A., S.K.-K., S.S., E.V.), University of Oulu; Medical Research Center Oulu (R.A.), Oulu University Hospital; Oulu City Hospital (R.A.), Finland; Department of Preventive Medicine and Public Health (H.A.), Fukuoka University, Japan; Guys and St Thomas' NHS Foundation Trust (N.B.), London, UK; University of Pittsburgh (J.C.B., M.G.), PA; Leiden University Medical Centre (A.S.B., S.T.), the Netherlands; University of Sheffield (A.B., J.P.), UK; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology (M.v.B., S.K.), Maastricht University, the Netherlands; University of Cambridge (C.B.), UK; University of California (M.C., C.K.), Irvine; University of Florida (S.D.), Gainesville; Albert Einstein College of Medicine (C.D., M.K.), New York, NY; University of Alberta (R.A.D., G.P.M.), Edmonton, Canada; International Longevity Centre (F.F.), Paris, France; University of Amsterdam (W.A.v.G., E.P.M.v.C.), the Netherlands; Golgi Cenci Foundation (A.G., R.V.), Milan, Italy; Trinity College Dublin (A.H., R.A.K.), Ireland; University of Calgary (D.B.H.), Canada; Newcastle University (C.J., B.C.M.S.), Newcastle upon Tyne; University of Bristol (P.G.K., S.K.K.), UK; University of Eastern Finland (J.L.), Kuopio; Faculty of Sport and Health Sciences, University of Jyväskylä (J.L.), Finland; School of Pharmacy, University of Waterloo (C.M.), Ontario, Canada; Academic Medical Center (T.v.M., E.R.), Amsterdam; Donders Institute for Brain, Cognition and Behaviour (T.v.M., E.R.), Radboud University Medical Center, Nijmegen, the Netherlands; National University of Singapore (T.-P.N.); Sengkang General Hospital (I.R.), Singhealth Duke-NUS Academic Medical Centre, Singapore; Dalhousie University (K.R.), Halifax, Canada; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy (L.R., I.S.), and Department of Psychology (J.S.), Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Sweden; University of Leuven (J.A.S., L.T.), Belgium; Bordeaux Population Health Research Center (P.J.T., C.T.), UMR 1219, CHU Bordeaux, University of Bordeaux, Inserm, France; University of Adelaide (P.J.T.); Australian National University (E.W.), Canberra, Australia; and University of Warwick (J.W.), Coventry, UK.

Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.

Methods: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.

Results: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.

Conclusion: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.

Clinical Trials Registration: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
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January 2020

The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study.

Cerebrovasc Dis Extra 2017 10;7(3):140-152. Epub 2017 Oct 10.

Alzheimer Center & Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.

Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol.

Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz-heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines.

Results And Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.
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July 2018

High Sensitivity Cardiac Troponin T and Cognitive Function in the Oldest Old: The Leiden 85-Plus Study.

J Alzheimers Dis 2017 ;60(1):235-242

Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.

Background: Impaired cardiac function has been related to accelerated cognitive decline in late-life.

Objective: To investigate whether higher levels of high sensitivity cardiac troponin T (hs-cTnT), a sensitive marker for myocardial injury, are associated with worse cognitive function in the oldest old.

Methods: In 455 participants of the population-based Leiden 85-plus Study, hs-cTnT was measured at 86 years. Cognitive function was measured annually during four years with the Mini-Mental State Examination (MMSE).

Results: Participants in the highest gender-specific tertile of hs-cTnT had a 2.0-point lower baseline MMSE score than participants in the lowest tertile (95% confidence interval (CI) (95% CI 0.73-3.3), and had a 0.58-point steeper annual decline in MMSE during follow-up (95% CI 0.06-1.1). The associations remained after adjusting for sociodemographic and cardiovascular risk factors excluding those without a history of overt cardiac disease.

Conclusion: In a population-based sample of the oldest old, higher levels of hs-cTnT were associated with worse cognitive function and faster cognitive decline, independently from cardiovascular risk factors and a history of overt cardiac disease.
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May 2018

Hemodynamic and serum cardiac markers and risk of cognitive impairment and dementia.

Alzheimers Dement 2017 Apr 19;13(4):441-453. Epub 2016 Oct 19.

Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Departments of Medicine and Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address:

Introduction: Cardiac function is a key player in maintaining energy homeostasis in the brain. Heart failure is closely related to higher risk of neurocognitive disorders. Recent evidence shows that this relationship might not be limited to patients with advanced heart failure, and even suboptimal cardiac functioning is associated with accelerated brain aging. Hence, hemodynamic and serum cardiac markers may provide valuable information about the risk of dementia.

Methods: We provide an overview on the link between cardiac markers and cognitive function by a systematic search in five databases. Furthermore, we discuss the pathophysiological aspects of this link and highlight the pertinent clinical and public health implications.

Results: Increasing evidence supports the associations of hemodynamic and serum cardiac markers with accelerated cognitive decline.

Discussion: Hemodynamic and serum cardiac markers are closely linked with risk of cognitive impairment. This highlights the significance of the heart-brain connection in reducing the burden of dementia.
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April 2017

Validity of the three apathy items of the Geriatric Depression Scale (GDS-3A) in measuring apathy in older persons.

Int J Geriatr Psychiatry 2017 04 7;32(4):421-428. Epub 2016 Apr 7.

Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands.

Objective: The Geriatric Depression Scale (GDS)-3A, a three-item subset of the GDS-15, is increasingly used as a measure for apathy in research settings to assess factors associating with this neuropsychiatric syndrome. We aimed to assess how accurately the GDS-3A discriminates between presence and absence of apathy in two populations of community-dwelling older persons, using the Apathy Scale as reference standard.

Methods: Baseline data were used from 427 participants of the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden and 1118 participants of the PROactive Management Of Depression in the Elderly (PROMODE) Study, all ≥75 years and with available GDS-3A and Apathy Scale measurements. A cut-off score of ≥14 was used for presence of apathy according to the Apathy Scale. Areas under the receiver operating characteristic curve (AUC) were calculated. Based on the likelihood ratios for GDS-3A scores, a cut-off of ≥2 was used for presence of apathy according to the GDS-3A to calculate test characteristics.

Results: The AUC was 0.68 (95% confidence interval 0.62-0.73) in the DANTE Study and 0.72 (0.67-0.77) in the PROMODE Study. In the DANTE Study sensitivity was 29.3% (21.4-38.1) and specificity was 88.5% (84.4-91.8), whereas in the PROMODE Study sensitivity was 32.8% (24.5-41.1) and specificity 92.6% (90.9-94.2). Stratification on population characteristics did not yield more favourable test characteristics.

Conclusion: The GDS-3A has low sensitivity and high specificity as a measure of apathy in two populations of older persons. Using the GDS-3A in research might yield estimates biassed towards the null in case of non-differential misclassification. Copyright © 2016 John Wiley & Sons, Ltd.
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April 2017

Effect of Discontinuation of Antihypertensive Treatment in Elderly People on Cognitive Functioning--the DANTE Study Leiden: A Randomized Clinical Trial.

JAMA Intern Med 2015 Oct;175(10):1622-30

Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands9Department of Psychiatry, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.

Importance: Observational studies indicate that lower blood pressure (BP) increases risk for cognitive decline in elderly individuals. Older persons are at risk for impaired cerebral autoregulation; lowering their BP may compromise cerebral blood flow and cognitive function.

Objective: To assess whether discontinuation of antihypertensive treatment in older persons with mild cognitive deficits improves cognitive, psychological, and general daily functioning.

Design, Setting, And Participants: A community-based randomized clinical trial with a blinded outcome assessment at the 16-week follow-up was performed at 128 general practices in the Netherlands. A total of 385 participants 75 years or older with mild cognitive deficits (Mini-Mental State Examination score, 21-27) without serious cardiovascular disease who received antihypertensive treatment were enrolled in the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden from June 26, 2011, through August 23, 2013 (follow-up, December 16, 2013). Intention-to-treat analyses were performed from January 20 through April 11, 2014.

Interventions: Discontinuation (n=199) vs continuation (n=186) of antihypertensive treatment (allocation ratio, 1:1).

Main Outcomes And Measures: Change in the overall cognition compound score. Secondary outcomes included changes in scores on cognitive domains, the Geriatric Depression Scale-15, Apathy Scale, Groningen Activity Restriction Scale (functional status), and Cantril Ladder (quality of life).

Results: Compared with 176 participants undergoing analysis in the control (continuation) group, 180 in the intervention (discontinuation) group had a greater increase (95% CI) in systolic BP (difference, 7.36 [3.02 to 11.69] mm Hg; P=.001) and diastolic BP (difference, 2.63 [0.34 to 4.93] mm Hg; P=.03). The intervention group did not differ from the control group in change (95% CI) in overall cognition compound score (0.01 [-0.14 to 0.16] vs -0.01 [-0.16 to 0.14]; difference, 0.02 [-0.19 to 0.23]; P=.84). The intervention and control groups did not differ significantly in secondary outcomes, including differences (95% CIs) in change in compound scores of the 3 cognitive domains (executive function, -0.07 [-0.29 to 0.15; P=.52], memory, 0.08 [-0.12 to 0.29; P=.43], and psychomotor speed, -0.85 [-1.72 to 0.02; P=.06]), symptoms of apathy (0.17 [-0.65 to 0.99; P=.68]) and depression (0.14 [-0.20 to 0.48; P=.41]), functional status (-0.72 [-1.52 to 0.09; P=.08]), and quality-of-life score (-0.09 [-0.34 to 0.16; P=.46]). Adverse events were equally distributed.

Conclusions And Relevance: In older persons with mild cognitive deficits, discontinuation of antihypertensive treatment did not improve cognitive, psychological, or general daily functioning at the 16-week follow-up.

Trial Registration: Identifier: NTR2829.
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October 2015

Lower blood pressure and apathy coincide in older persons with poorer functional ability: the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden.

J Am Geriatr Soc 2015 Jan;63(1):112-7

Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.

Objectives: To examine the association between blood pressure (BP) measures and symptoms of apathy and depression in older adults with various levels of functional ability.

Design: Cross-sectional study using baseline data from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden.

Setting: Primary care setting, the Netherlands.

Participants: Community-dwelling individuals aged 75 and older (N = 430).

Measurements: Systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were measured during home visits. Symptoms of apathy and depression were assessed using the Apathy Scale and the Geriatric Depression Scale (GDS-15), respectively. Stratified linear regression was performed in participants with better and worse functional ability according to the median of the Groningen Activity Restriction Scale.

Results: In participants with lower functional ability, each 10-mmHg lower SBP, DBP, and MAP was associated with higher Apathy Scale scores (0.63, 0.92, and 0.94 points, respectively, all P < .005) but not with GDS-15 scores. In participants with higher functional ability, BP measures were not associated with Apathy Scale or GDS-15 scores.

Conclusion: In older participants with poorer functional ability, lower BP was associated with more symptoms of apathy but not depression.
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January 2015

Associated autoimmune diseases in patients with multifocal motor neuropathy and their family members.

J Neurol 2012 Jun 23;259(6):1137-41. Epub 2011 Nov 23.

Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

Multifocal motor neuropathy (MMN) is a rare immune-mediated disorder and is characterized by male predominance, the presence of serum anti-GM1 IgM antibodies in up to half of all patients, responsiveness to intravenous immunoglobulins (IVIg) and an increased frequency of HLA type HLA-DRB1*15. The aim of this study was to assess whether the frequency of autoimmune diseases (AID) is increased in patients with MMN and their first-degree family members, since this would indicate that MMN shares pathogenic mechanisms with other AID. We conducted a case-control study using questionnaires to evaluate the prevalence of AID in MMN and controls, and their first-degree relatives. Questionnaires from 81 MMN patients (417 first-degree relatives) and 438 controls (2,377 first-degree relatives) were analyzed. Overall prevalence of AID was higher in MMN patients (11%) than in controls (5%) (OR 2.4, 95% CI 1.1-5.5, p = 0.037). Type 1 diabetes, Hashimoto's thyroid disease, and celiac disease were significantly more prevalent in family members of patients than controls. The presence of an additional AID was not associated with age at MMN onset, disease duration, titer of serum anti-GM1 IgM antibodies or HLA type HLA-DRB1*15. The higher frequency of AID in patients with MMN indicates a common autoimmune diathesis.
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June 2012