Tuesday, June 25, 2019

Commonly Prescribed Drug Likely Increases of Dementia

The study, carried out by experts from the University of Nottingham and funded by the NIHR School for Primary Care Research, found that there was nearly a 50% increased risk of dementia among patients aged 55 and over who had used strong anticholinergic medication daily for three years or more.

Anticholinergic drugs help to contract and relax muscles. They work by blocking acetylcholine, a chemical that transmits messages in the nervous system.

Credit: University of Nottingham

Doctors prescribe the drugs to treat a variety of conditions, including chronic obstructive pulmonary disease, bladder conditions, allergies, gastrointestinal disorders and symptoms of Parkinson's disease.

These medicines can have short-term side effects, including confusion and memory loss, but it is less certain whether long-term use increases the risk of dementia.

The research, published in the JAMA Internal Medicine journal and led by Professor Carol Coupland from the University's Division of Primary Care, looked at the medical records of 58,769 patients with a diagnosis of dementia and 225,574 patients without a diagnosis of dementia, all aged 55 and over and registered with UK GPs contributing data to the QResearch database, between 1 January 2004 and 31 January 2016.

The study findings showed increased risks of dementia for anticholinergic drugs overall and specifically for the anticholinergic antidepressants, antipsychotic drugs, antiparkinsons drugs, bladder drugs and epilepsy drugs after accounting for other risk factors for dementia.

No increased risks were found for the other types of anticholinergic drug studied such as antihistamines and gastrointestinal drugs.

Professor Tom Dening, Head of the Centre for Dementia at the University of Nottingham and a member of the research study team, said: "This study provides further evidence that doctors should be careful when prescribing certain drugs that have anticholinergic properties. However, it's important that patients taking medications of this kind don't just stop them abruptly as this may be much more harmful. If patients have concerns, then they should discuss them with their doctor to consider the pros and cons of the treatment they are receiving."

The 58,769 patients with dementia had an average age of 82 and 63% were women. Each dementia case was matched to five control patients of the same age, sex, and general practice.

Anticholinergic drug exposure was assessed using prescription information over a complete period of 10 years from 1 to 11 years before diagnosis of dementia or the equivalent dates in control patients, and was compared between the two patient groups. Further analysis looked at prescriptions for anticholinergic drugs up to 20 years before diagnosis of dementia.

This is an observational study so no firm conclusions can be drawn about whether these anticholinergic drugs cause dementia, and it is possible that the drugs were being prescribed for very early symptoms of dementia.

Professor Coupland said: "Our study adds further evidence of the potential risks associated with strong anticholinergic drugs, particularly antidepressants, bladder antimuscarinic drugs, anti-Parkinson drugs and epilepsy drugs.

"The risks of this type of medication should be carefully considered by healthcare professionals alongside the benefits when the drugs are prescribed and alternative treatments should be considered where possible, such as other types of antidepressants or alternative types of treatment for bladder conditions. These findings also highlight the importance of carrying out regular medication reviews.

"We found a greater risk for people diagnosed with dementia before the age of 80 which indicates that anticholinergic drugs should be prescribed with caution in middle-aged people as well as in older people."

These results, along with those of a similar study published in 2018 help to clarify which types of anticholinergic drug are associated with the highest risks of dementia.

In the 1-11 years before the dementia diagnosis date or equivalent in controls, nearly 57% of cases and 51% of controls were prescribed at least one strong anticholinergic drug, with an average of six prescriptions in cases and 4 in controls. The most frequently-prescribed types of drugs were antidepressants, anti-vertigo and bladder antimuscarinic drugs - which are used to treat an overactive bladder.

The increased risk associated with these drugs indicates that if the association is causal around 10% of dementia diagnoses could be attributable to anticholinergic drug exposure, which would equate to around 20,000 of the 209,600 new cases of dementia per year in the UK.

This is a sizeable proportion and is comparable with other modifiable risk factors for dementia, including 5% for midlife hypertension, 3% for diabetes, 14% for later life smoking and 6.5% for physical inactivity.

Contacts and sources:
Charlotte AnscombeUniversity of Nottingham


Stellar Heavyweight Champion of Dying Stars

Dying stars that cast off their outer envelopes to form the beautiful yet enigmatic "planetary nebulae" (PNe) have a new heavy-weight champion, the innocuously named PNe "BMP1613-5406". Massive stars live fast and die young, exploding as powerful supernovae after only a few million years. 

However, the vast majority of stars, including our own Sun, have much lower mass and may live for many billions of years before going through a short lived but glorious PNe phase. PNe form when only a tiny fraction of unburnt hydrogen remains in the stellar core. Radiation pressure expels much of this material and the hot stellar core can shine through. This ionizes the previously ejected shroud creating a PNe and providing a visible and valuable fossil record of the stellar mass loss process (PNe have nothing to do with planets but acquired this name because their glowing spheres of ionized gas around their hot central stars resembled planets to early observers).

This is a 30 x 30 arcminute image of NGC6067 & BMP1613-5406. North-East is top left. The image is a B,R,H-alpha tri-colour RGB image (extracted from the online UK Schmidt Telescope SuperCOSMOS H-alpha Survey H-alpha, short-Red (SR) and broad-band 'B' images.
Credit: @The University of Hong Kong

PNe theoretically derive from stars in the range 1-8 times the mass of the Sun, representing 90% of all stars more massive than the sun. However, until now, PNe have been proven to derive from stars born with only 1-3 times the mass of our Sun. Professor Quentin Parker, Department of Physics and Director of The Laboratory for Space Research, The University of Hong Kong and his PhD student Miss Fragkou Vasiliki, in collaboration with University of Manchester and South African Astronomical Observatory, have now officially smashed this previous limit and grabbed the proof that a PNe has emerged from a star born with 5.5 times the mass of our Sun. Their journal paper "A high-mass planetary nebula in a Galactic open cluster" has just been published on the Nature Astronomy's website.

But why is this important?

Firstly, PNe provide a unique window into the soul of late stage stellar evolution revealed by their rich emission line spectra that are excellent laboratories for plasma physics. PNe are visible to great distances where their strong lines permit determination of the size, expansion velocity and age of the PN, so probing the physics and timescales of stellar mass loss. They can also be used to derive luminosity, temperature and mass of their central remnant stellar cores, and the chemical composition of the ejected gas.

Secondly, and key here, is that this is an unprecedented example of a star whose proven original "progenitor" mass is close to the theoretical lower limit of core-collapse supernova formation. Our results are the first solid evidence confirming theoretical predictions that 5+ solar mass stars can actually form PNe. This unique case therefore provides the astronomical community with an important tool for fresh insights into stellar and Galactic chemical evolution.

A VPHAS+ combined u g r multi-band 'RGB' color image centred on the planetary nebula central star (CS) candidate. The image is 55 x 55 arcseconds in size and the CS is obvious as the sole blue star in the middle of field, located at RA:16h13m02.1s and DEC:-54o06'32.3" (J2000).
Credit: @The University of Hong Kong

But how did the team from The University of Hong Kong and the University of Manchester claim the heavyweight crown?

The key was the discovery of the PNe in a young, Galactic open cluster called NGC6067. Finding a PNe residing in an open cluster is an extremely rare event. Indeed, only one other PNe, "PHR1615-6555" has ever been previously proven to reside on an open cluster but whose progenitor star had considerably lower mass. Interestingly, this was an earlier discovery from the same led team as here. The proven location of a PN in a cluster provides key and important data that is difficult to acquire otherwise. This includes an accurate distance and a cluster "turn off" mass estimate (i.e. the mass a star must have had when it was born to now be seen evolving off the main sequence in the cluster of known age). High confidence in the PN-cluster association comes from their highly consistent radial velocities (to better tan 1km/s) in a sight-line with a steep velocity-distance gradient, common distances, common reddening and projected and close physical proximity of the PN to the cluster centre.

A current plot from cluster WDs for the latest IFMR estimates from Cummings et al (2018), together with our estimated point for BMP1613-5406 plotted as a red circle. The only other point from a known OC PN is plotted as a yellow circle (Parker et al 2011). The errors attached to our point reflect the errors in the adopted cluster parameters and the spread of the estimated CS magnitudes.
Credit: @The University of Hong Kong

In summary our exciting results are solid evidence confirming theoretical predictions that 5+ solar mass stars can form planetary nebulae and are, as expected, Nitrogen rich. The PN's cluster membership provides fresh and tight constraints on the lower mass limit for the progenitor mass of core-collapse supernovae and also for the intermediate to high mass end of the white dwarf Initial to Final Mass Relation (IFMR). It also provides an empirical benchmark for evaluating nucleosynthetic (element creation) predictions for intermediate-mass stars. PN BMPJ1613-5406 and its cluster NGC6067 will provide the astronomical community with important insights into stellar and Galactic (chemical) evolution.

Contacts and sources:
Cindy ChanThe University of Hong Kong

Citation: A high-mass planetary nebula in a Galactic open cluster V. Fragkou, Q. A. Parker, A. A. Zijlstra, L. Crause & H. Barker Nature Astronomy (2019) https://www.nature.com/articles/s41550-019-0796-x http://dx.doi.org/10.1038/s41550-019-0796-x