Association of arterial stiffness with progression of subclinical brain and cognitive disease.

Posted on February 17, 2016 by Maurice Preter MD

Association of arterial stiffness with progression of subclinical brain and cognitive disease.

http://tinyurl.com/jcqsplz

Tsao CW1, Himali JJ2, Beiser AS2, Larson MG2, DeCarli C2, Vasan RS2, Mitchell GF2, Seshadri S2.

Author information

Abstract

OBJECTIVE:

We tested whether abnormal arterial stiffness and blood pressure would be associated with progression of brain aging measured by brain MRI and neurocognitive testing.

METHODS:

Framingham Offspring Cohort participants (n = 1,223, 61 ± 9 years, 56% women) without previous stroke or dementia underwent applanation tonometry, brain MRI, and neurocognitive testing at examination 7 (1998-2001). Follow-up brain MRI and neurocognitive testing was performed at examination 8 (2005-2008, mean interval 6.4 ± 1.3 years). We related examination 7 inverse-transformed carotid-femoral pulse wave velocity (iCFPWV), central pulse pressure (CPP), and mean arterial pressure to changes in the following variables between examinations 7 and 8: total cerebral brain volume, white matter hyperintensity volume, and performance on executive function and abstraction tasks, the Trail Making Test, Parts B and A (ΔTrails B-A), and Similarities tests.

RESULTS:

Higher baseline iCFPWV and CPP were associated with greater progression of neurocognitive decline (iCFPWV and ΔTrails B-A association: SD unit change in outcome variable per SD change in tonometry variable [β] ± SE = 0.10 ± 0.04, p = 0.019; CPP and ΔSimilarities association: -0.08 ± 0.03, p = 0.013). Higher mean arterial pressure, but not iCFPWV or CPP, was associated with increase in white matter hyperintensity volume ([β ± SE] 0.07 ± 0.03, p = 0.017). No tonometry measures were associated with change in cerebral brain volume.

CONCLUSIONS:

In middle-aged and older adults without evidence of clinical stroke or dementia, elevated arterial stiffness and pressure pulsatility are associated with longitudinal progression of subclinical vascular brain injury and greater neurocognitive decline. Treatments to reduce arterial stiffness may potentially reduce the progression of neurovascular disease and cognitive decline.

© 2016 American Academy of Neurology.

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Midlife exercise blood pressure, heart rate, and fitness relate to brain volume 2 decades later

Posted on February 17, 2016 by Maurice Preter MD

Midlife exercise blood pressure, heart rate, and fitness relate to brain volume 2 decades later

http://tinyurl.com/zzlgg8k

Nicole L. Spartano, PhD, Jayandra J. Himali, PhD, Alexa S. Beiser, PhD, Gregory D. Lewis, MD, Charles DeCarli, MD, Ramachandran S. Vasan, MD and Sudha Seshadri, MD

+SHOW AFFILIATIONS | + SHOW FULL DISCLOSURES

Correspondence to Dr. Spartano: spartano@bu.edu

Published online before print February 10, 2016doi:http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002415Neurology 10.1212/WNL.0000000000002415

ABSTRACT

Objective: To determine whether poor cardiovascular (CV) fitness and exaggerated exercise blood pressure (BP) and heart rate (HR) were associated with worse brain morphology in later life.

Methods: Framingham Offspring participants (n = 1,094, 53.9% female) free from dementia and CV disease (CVD) underwent an exercise treadmill test at a mean age of 40 ± 9 years. A second treadmill test and MRI scans of the brain were administered 2 decades later at mean age of 58 ± 8 years.

Results: Poor CV fitness and greater diastolic BP and HR response to exercise at baseline were associated with a smaller total cerebral brain volume (TCBV) almost 2 decades later (all p < 0.05) in multivariable adjusted models; the effect of 1 SD lower fitness was equivalent to approximately 1 additional year of brain aging in individuals free of CVD. In participants with prehypertension or hypertension at baseline, exercise systolic BP was also associated with smaller TCBV (p < 0.05).

Conclusion: Our results suggest that lower CV fitness and exaggerated exercise BP and HR responses in middle-aged adults are associated with smaller brain volume nearly 2 decades later. Promotion of midlife CV fitness may be an important step towards ensuring healthy brain aging.

Received August 11, 2015.

Accepted in final form December 14, 2015.

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Association of Proton Pump Inhibitors With Risk of Dementia

Posted on February 17, 2016 by Maurice Preter MD

Association of Proton Pump Inhibitors With Risk of Dementia

A Pharmacoepidemiological Claims Data Analysis

http://tinyurl.com/zx9n3o8

Willy Gomm, PhD1; Klaus von Holt, MD, PhD1; Friederike Thomé, MSc1; Karl Broich, MD2; Wolfgang Maier, MD1,3; Anne Fink, MSc1,4; Gabriele Doblhammer, PhD1,4,5,6; Britta Haenisch, PhD1

 

 

JAMA Neurol. Published online February 15, 2016. doi:10.1001/jamaneurol.2015.4791

ABSTRACT

Importance  Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.

Objective  To examine the association between the use of PPIs and the risk of incident dementia in the elderly.

Design, Setting, and Participants  We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015.

Exposures  Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.

Main Outcomes and Measures  The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy.

Results  A total of 73 679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).

Conclusions and Relevance  The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.

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The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis

Posted on February 12, 2016 by Maurice Preter MD

 

The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis

http://tinyurl.com/jur423x

Anick Bérard1,2,*, Noha Iessa1,2, Sonia Chaabane1,2, Flory T. Muanda1,2, Takoua Boukhris1,2 and Jin-Ping Zhao1,2

Article first published online: 26 JAN 2016

DOI: 10.1111/bcp.12849

Abstract

Aims

The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category.

Method

A systematic review of studies published between 1966 and November 2015 was conducted using embase and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models.

Results

Twenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n = 15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n = 18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n = 4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n = 4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed.

Conclusions

Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.

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Antidepressant Use Is Associated With an Increased Risk of Developing Microbleeds

Posted on February 12, 2016 by Maurice Preter MD

 

Antidepressant Use Is Associated With an Increased Risk of Developing Microbleeds

http://tinyurl.com/z96cjhk

Saloua Akoudad, MD, PhD*; Nikkie Aarts, MSc*; Raymond Noordam, PhD; M. Arfan Ikram, MD, PhD; Henning Tiemeier, MD, PhD; Albert Hofman, MD, PhD; Bruno H. Stricker, MMed, PhD; Meike W. Vernooij, MD, PhD; Loes E. Visser, PharmD, PhD

+Author Affiliations

From the Departments of Epidemiology (S.A., N.A., R.N., M.A.I., H.T., A.H., B.H.S., M.W.V., L.E.V.), Radiology (S.A., M. A.I., M.W.V.), Neurology (S.A., M.A.I.), Internal Medicine (N.A., R.N., B.H.S., L.E.V.), Psychiatry (H.T.), and Department of Child and Adolescent Psychiatry (H.T.), Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Inspectorate of Health Care, Utrecht, The Netherlands (B.H.S.); and Apotheek Haagse Ziekenhuizen – HAGA, the Hague, The Netherlands (L.E.V.).
 

Correspondence to Bruno H. Stricker, MMed, PhD, Erasmus MC, 3000 CA Rotterdam, The Netherlands. E-mail b.stricker@erasmusmc.nl

Abstract

Background and Purpose—Serotonin-specific antidepressants may increase the risk of adverse bleeding events. In a previous cross-sectional study, we did not observe an association between antidepressant use and presence of subclinical cerebral bleedings. In this study, we investigated longitudinally whether antidepressant use is associated with an increased risk of new subclinical cerebral microbleeds.

Methods—In total, 2559 participants aged ≥45 years of the population-based Rotterdam Study, all without microbleeds at baseline, underwent baseline and repeat brain magnetic resonance imaging between 2005 and 2013 (mean time interval, 3.9 years; SD, 0.5) to determine the incidence of microbleeds. Antidepressant use (yes versus no) was assessed between baseline and follow-up scan. In additional analyses, antidepressants were classified as low, intermediate, or high affinity for the serotonin transporter, and alternatively as selective serotonin reuptake inhibitors or non-selective serotonin reuptake inhibitors. We used multivariable logistic regression models to investigate the association of antidepressants with incident microbleeds.

Results—Antidepressant use was associated with a higher cerebral microbleed incidence (odds ratio, 2.22; 95% confidence interval, 1.31–3.76) than nonuse. When stratified by affinity for the serotonin transporter, intermediate serotonin affinity antidepressant use was associated with an increased risk of developing microbleeds (odds ratio, 3.07; 95% confidence interval, 1.53–6.17). Finally, selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor use were both associated with increased microbleed incidence.

Conclusions—Antidepressant use was associated with an increased risk of developing microbleeds. Our results may support findings from previous clinical studies about increased intracranial and extracranial bleeding risk in antidepressant

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