Heritability of frontotemporal dementia

One of my side projects over the past 2 years has been research in the cognitive neurosciences under the supervision of Dr James Burrell at Neuroscience Research Australia (NeuRA). Specifically, we were looking at the heritability of frontotemporal dementia.

Preliminary results from our study were published as a poster at the Australian and New Zealand Association of Neurologists (ANZAN) Annual Scientific Meeting 2014 in Adelaide. I doubt that anyone else at a neurology conference would typeset a poster in Helvetica Neue Light!

Our poster at ANZAN ASM 2014

This culminated in a paper which was accepted in the Journal of Neurology and published in November 2014 (vol 261 no 11). The abstract is reproduced below, along with the correct author affiliations (an error was introduced by the journal subeditors – Professors Kwok, Halliday and Hodges are not affiliated with Concord Repatriation General Hospital).

Po et al. J Neurol 2014

Author Affiliations

Concord Repatriation General Hospital, Sydney, Australia – KP, JB
Sydney Medical School, The University of Sydney, Australia – KP
Neurosciences Research Australia, Sydney, Australia – FL, NG, LB, JK, GH, JH, JB
The University of New South Wales, Sydney, Australia – JK, GH, JH, JB

Abstract

Frontotemporal dementia (FTD) is reportedly highly heritable, even though a recognized genetic cause is often absent. To explain this contradiction, we explored the “strength” of family history in FTD, Alzheimer’s disease (AD), and controls. Clinical syndromes associated with heritability of FTD and AD were also examined. FTD and AD patients were recruited from an FTD-specific research clinic, and patients were further sub-classified into FTD or AD phenotypes. The strength of family history was graded using the Goldman score (GS), and GS of 1-3 was regarded as a “strong” family history. A subset of FTD patients underwent screening for the main genetic causes of FTD. In total, 307 participants were included (122 FTD, 98 AD, and 87 controls). Although reported positive family history did not differ between groups, a strong family history was more common in FTD (FTD 17.2 %, AD 5.1 %, controls 2.3 %, P < 0.001). The bvFTD and FTD-ALS groups drove heritability, but 12.2 % of atypical AD patients also had a strong family history. A pathogenic mutation was identified in 16 FTD patients (10 C9ORF72 repeat expansion, 5 GRN, 1 MAPT), but more than half of FTD patients with a strong family history had no mutation detected. FTD is a highly heritable disease, even more than AD, and patients with bvFTD and FTD-ALS drive this heritability. Atypical AD also appears to be more heritable than typical AD. These results suggest that further genetic influences await discovery in FTD.

Citation

Po K, Leslie FVC, Gracia N, Bartley L, Kwok JBJ, Halliday GM, Hodges JR, Burrell JR. Heritability in frontotemporal dementia: more missing pieces? J Neurol. 2014;261(11):2170–7.

doi: 10.1007/s00415-014-7474-9
PMID: 25156163 (PubMed)

Peer-reviewed and published!

Over a four-month period in summer 2007/08, I was involved in public health research at the National Centre for Immunisation Research and Surveillance (NCIRS) on a Faculty of Medicine Summer Research Scholarship. The results from that work have now been published in the journal BMC Health Services Research, which means that I now have my first peer-reviewed journal article to my name. The full text of our article (open access) is available from BioMed Central.

Seale, et al. BMC Health Serv Res 2009.

Abstract

Background: There is a general consensus that another influenza pandemic is inevitable. Although health care workers (HCWs) are essential to the health system response, there are few studies exploring HCW attitudes to pandemic influenza. The aim of this study was to explore HCWs knowledge, attitudes and intended behaviour towards pandemic influenza.

Methods: Cross-sectional investigation of a convenience sample of clinical and non-clinical HCWs from two tertiary-referral teaching hospitals in Sydney, Australia was conducted between June 4 and October 19, 2007. The self-administered questionnaire was distributed to hospital personal from 40 different wards and departments. The main outcome measures were intentions regarding work attendance and quarantine, antiviral use and perceived preparation.

Results: Respondents were categorized into four main groups by occupation: Nursing (47.5%), Medical (26.0%), Allied (15.3%) and Ancillary (11.2%). Our study found that most HCWs perceived pandemic influenza to be very serious (80.9%, n = 873) but less than half were able to correctly define it (43.9%, n = 473). Only 24.8% of respondents believed their department to be prepared for a pandemic, but nonetheless most were willing to work during a pandemic if a patient or colleague had influenza. The main determinants of variation in our study were occupational factors, demographics and health beliefs. Non-clinical staff were significantly most likely to be unsure of their intentions (OR 1.43, p < 0.001). Only 42.5% (n = 459) of respondents considered that neuraminidase inhibitor antiviral medications (oseltamivir/zanamivir) would protect them against pandemic influenza, whereas 77.5% (n = 836) believed that vaccination would be of benefit.

Conclusion: We identified two issues that could undermine the best of pandemic plans – the first, a low level of confidence in antivirals as an effective measure; secondly, that non-clinical workers are an overlooked group whose lack of knowledge and awareness could undermine pandemic plans. Other issues included a high level of confidence in dietary measures to protect against influenza, and a belief among ancillary workers that antibiotics would be protective. All health care worker strategies should include non clinical and ancillary staff to ensure adequate business continuity for hospitals. HCW education, psychosocial support and staff communication could improve knowledge of appropriate pandemic interventions and confidence in antivirals.

Citation/identifiers

Seale H, Leask J, Po K, MacIntyre CR. “Will they just pack up and leave?” – attitudes and intended behaviour of hospital health care workers during an influenza pandemic. BMC Health Serv Res. 2009;9:30.

doi:10.1186/1472-6963-9-30
PMID: 19216792 (PubMed)

A tale of four tutors

Four tutors at two Group of Eight universities in Sydney in the past two weeks: an allegory on some of the qualities of good teachers…

Tutor A teaches medicine. Although qualified in a clinical health science, she had little understanding of the subject material nor demonstrated any convincing attempt to do so. She did not attempt to establish rapport with the students in her class.

Tutor B teaches clinical sciences. Whilst clearly qualified in the majority of the subject material taught, he then attempted to teach some material which he didn’t understand (in a field where some of the graduate students in the class were qualified). He did, however, attempt to establish rapport with the students in his class with some success.

Tutors C & D teach in the Faculty of Pharmacy at USyd and the Faculty of Medicine at UNSW respectively. Although both are relatively young, they proactively ensure that they each have a thorough knowledge and understanding of the material taught. Appreciating the importance of connecting with students, they both make a high priority of establishing good rapport with the students in their respective classes.

Who would you prefer as your tutor?