Cohort Profile: The Hunter Community Study

In almost every country, the proportion of people aged >60 years is growing faster than any other age group and is expected to reach 2 billion worldwide by 2050.1 Internationally and nationally, considerable efforts are being made to promote active ageing.2–4 However, Australia lacks the kind of comprehensive longitudinal research underway in Europe and North America.5,6 Although Australia does have a number of longitudinal studies designed to address various issues of health and ageing among older adults,7,8 only a few of these studies include a broad and comprehensive range of physical and biological measures. The Hunter Community Study (HCS) is a collaborative study between the University of Newcastle’s School of Medicine and Public Health and the Hunter New England Area Health Service. It is a multi disciplinary initiative that was established to fill some existing gaps in ageing research in Australia and is unique in that it has collected detailed information across all six key policy themes as identified in the Framework for an Australian Ageing Research Agenda.9 The HCS is a population-based cohort study established to assess factors important in the health, well-being, social functioning and economic consequences of ageing. More specifically, the aims of the HCS study are to provide: a broad spectrum of measures of ageing that includes clinical, genetic, biochemical, health services, economic, environmental as well as social and behavioural measures; sufficient statistical power to test a range of important hypotheses about common acute and chronic disease events, i.e. percentage incidence of a particular disease over 10-year follow-up; a comparison population for studies involving the use of case series from local hospitals; a repository of stored biological samples, covering plasma, serum, whole blood, DNA and whole cells; virtual follow-up through individual-level linkage with databases including Medicare Australia, Pharmaceutical Benefits Scheme, hospital separations, cancer, cardiovascular disease, death and other registries; and a reference population for economic, social science, environmental, health services, health promotion, clinical and genetic research. The HCS is a cohort of community-dwelling men and women aged 55–85 years of age who reside in Newcastle, New South Wales (NSW), Australia (Figure 1). Participants were randomly selected from the NSW State electoral roll and contacted between December 2004 and December 2007. Listing on the electoral role is compulsory in Australia, and its content is estimated to be 93.6% correct.10 A modified Dillman recruiting strategy11 was used for this study, wherein two letters of introduction and an invitation to participate were posted to the selected persons. Individuals who did not respond to initial postal contacts were telephoned by an HCS research assistant where a publicly listed number was available. If contact was not established after five attempts, the individual was classified as a non-responder. Persons who could not speak English and those living in a residential aged-care facility were deemed ineligible. Location of the HCS: Newcastle, Hunter Region, NSW, Australia Following consent to participate, subjects were asked to complete two self-report questionnaires and to return these when they attended the HCS data collection centre (clinic) during which time a series of clinical measures was obtained (Figure 2). Consent from participants to link personal information obtained during the study to data from Medicare Australia (Medicare and Pharmaceutical Benefit Scheme) and local health databases was also sought at this time. A package of three further self-reporting questionnaires to be returned by reply-paid post was given to participants to complete at home following their clinical assessment. Splitting the questionnaire administration before and after the clinical phase in this manner was intended to reduce respondent burden and thereby maximize participant attendance for clinical assessments. Measures in the HCS Invitation letters were sent to 9784 individuals randomly selected from the Australian electoral roll. Of the 7575 subjects for whom a response was received either in person or from a relative, 258 were ineligible (148 did not speak English, 92 were deceased and 18 had moved to an aged-care institution), 3440 refused and 3877 agreed to participate. A total of 3253 actually participated (response rate 44.5%). Comparisons between responders and non-responders revealed no statistically significant difference for gender but a slightly younger age [mean age of 66.3 years vs 68.6 years, respectively, mean age difference 1.49 years, t = 0.4, P < 0.001, 95% confidence interval (CI) 0.78–2.19]. The HCS participants (Table 1) provide a population profile approximately reflecting that of the Hunter (NSW, Australia) state and national Australian profiles in terms of gender and marital status, but slightly younger in age12,13 (Table 6). Baseline Socio-demographic characteristics of participants in The Hunter Community Study Baseline Socio-demographic characteristics of participants in The Hunter Community Study The self-report postal questionnaires covered a wide range of variables (Figure 2). Demographics, e.g. age, education, housing, income, government benefits (Tables 1 and 2). Morbidity (self-reported diseases) (Table 4) and health professional utilization. Complementary and alternative medicines and medication use. Nutrition, using a Food Frequency Questionnaire.14 Quality of life, using Short Form 36 (SF-36)15 and Australian Quality of Life—Mark 2 (AQoL II).16 Physical activity, using the PASE.17 Mental health, using the Kessler Psychological Distress scale (K 10),18 CESD19 and a MACQ20 (Table 3). Daytime sleepiness, using the Epworth Sleepiness Scale.21 Social support, using the Duke Social Support Index (DSSI).22 Occupational exposures using a unique lifetime job history calendar wherein this information is coded using the FINJEM23 enabling determination of occupational exposure to more than 40 different classes of toxins, a measure particularly relevant for studies of occupational cancer. The job history calendar also allows more in-depth assessment of exposures using follow-up job-specific modules.24 The clinic measurements included: anthropometric: height, weight, waist-circumference; cardiovascular: blood pressure and heart rate; neurological/cognition: MMSE,25 Audio-Recorded Cognitive Screen Neuropsychological battery,26 hearing (using pure-tone audiometry) and vision (using Snellen chart); respiratory: spirometry; bone mineral density, using heel ultrasound; and functional capacity: functional reach,27 grip strength (using a dynamometer) and mobility using the ‘timed up and go’ test.28 Some of the unique measures included: peripheral vibration sensory testing using biothesiometry, a vibrating probe with a rheostat where increasing voltage increases the magnitude of the excursion of the probe;29 olfaction, using ‘Sniffin Sticks’ (Burghart Medical Technology, Wedel, Germany); scented markers with caps are exposed to a subject for a 30-s time interval at a 2-cm distance from the nostrils; 12 different smells are to be identified correctly.30 Given that olfactory neurons represent some of the most exposed nerve cells in the body, it has been suggested that changes in olfaction can be the harbinger of neurotoxic exposures31 or degenerative changes, e.g. Alzheimer’s disease;32–36 pedometer worn for 7 consecutive days during waking hours to record step count (Table 2). Biological measures assessed (Table 5) include: electrolytes, urea, creatinine; full blood count; fasting total cholesterol, as well as low density lipids (LDLs) and triglycerides (TGs); liver function tests; fibrinogen; and fasting blood glucose. Lifestyle and social factors in participants joining the HCS aMultiple responses permitted. Lifestyle and social factors in participants joining the HCS aMultiple responses permitted. Mental health and wellbeing of participants joining the Hunter Community Study Mental health and wellbeing of participants joining the Hunter Community Study Medical and Surgical history of participants joining the HCS Medical and Surgical history of participants joining the HCS Biochemical and haematological measures of participants joining the HCS Biochemical and haematological measures of participants joining the HCS Comparison of age and sex distribution between HCS and Hunter Valley, NSW, and the national population ahttp://www.abs.gov.au/census. Australian Bureau of Statistics. Population Census, 2001. bhttp://www.abs.gov.au/census. Australian Bureau of Statistics. Population by age and sex, 2005. Freq. = frequency. Comparison of age and sex distribution between HCS and Hunter Valley, NSW, and the national population ahttp://www.abs.gov.au/census. Australian Bureau of Statistics. Population Census, 2001. bhttp://www.abs.gov.au/census. Australian Bureau of Statistics. Population by age and sex, 2005. Freq. = frequency. In total, >90% of participants provided blood samples. Additionally, further samples in the form of serum, plasma and whole blood have been cryopreserved at –80°C for future use. All the cryopreserved blood samples are stored in 1-ml aliquots to minimize freeze–thaw cycles, which may adversely impact on analyte integrity. One of the more unique samples is whole blood that has been cryopreserved with dimethyl sulphoxide (DMSO)37 in liquid nitrogen to obtain whole lymphocytes for future cell immortalization (through Epstein–Barr virus transformation) and cytogenetic studies. These samples also allow for assaying biomarkers of genetic damage, in which toxins have affected DNA integrity. These include single- or double-stranded DNA breaks detected using the COMET assay, micronuclei, sister chromatid exchanges and cytogenetic abnormalities,38 all of which require whole viable cells, not just isolated DNA. It is planned that the cohort will be followed up with repeat questionnaires and a clinical assessment every 5 years to update exposure and outcome information. Funding has recently been provided to conduct a survey follow-up that will commence at the beginning of 2010. A total of >95% of study participants have consented to linkage of their study data with local and national health information databases and hospital records. These databases will provide virtual follow-up and information on mortality from the national death index; use of prescription medication and health service utilization from Medicare Australia; cancer incidence from the NSW cancer register and cardiovascular disease incidence from the Hunter Region Heart and Stroke register. Linkage to hospital records will provide more detailed information on hospitalizations, morbidity and mortality. To date, follow-up has been performed on subsets of participants for various sub-studies, which include: linkage of study information with the Medicare Australia database for the first 1000 study participants, to ascertain pneumococcal vaccination status; follow-up of 100 participants to perform further in-depth neuropsychological testing; follow-up of 120 participants to determine carotid intima-media thickness and a new non-invasive, computer-based test for occult cerebral ischaemia; and follow-up of the first 1000 participants via a self-administered survey of respiratory symptoms related to asthma and chronic obstructive pulmonary disease (COPD). As of May 2009, linkage to the national death index indicates that 70 (2%) participants are deceased. Only 30 participants have actively withdrawn from the study. Estimates of participants lost to follow-up will be available following the 2010 postal survey. However, early indications suggest that the cohort is particularly committed. Two years after recruitment, for example, 1060 participants received a self-administered survey asking about respiratory symptoms related to asthma and COPD. Despite survey administration coinciding with a severe cyclonic storm that flooded many areas in the Newcastle and Hunter region, the response rate was an encouraging 84%. Such participant commitment is a key strength of the study. Normative age and gender-specific reference ranges and percentiles of pedometer step counts were generated from data obtained from the first 1000 HCS participants. Median daily step count was 8605 in those aged 55–59 years, declining to 3778 in those aged >80 years. A total of 8000 steps/day was reached by 62% subjects aged 55–59 years and 12% aged >80 years.39 Our finding that women have higher step counts than men contradicts some other population studies of step counts. The questionnaire-based measure of physical activity (PASE score) and pedometer step counts were poorly correlated, with the latter showing much better correlation with surrogate markers of cardiovascular health, e.g. fibrinogen, white blood cell count, cholesterol and BMI.40 Normative age and gender reference ranges for vibratory perception threshold measures were obtained on 901 HCS participants free of known disease related to peripheral neuropathy. The vibration threshold was statistically significantly higher in the upper limb than in the lower limb.41 HCS participants have served as genetic controls for a variety of hospital-based case studies looking at complex disease risk. Polymorphisms in the genes for TP53, MDM2, Cyclin DI and oestrogen receptors (ESR1 and ESR2) have been shown to be associated with high-grade endometrial cancer.42–44 Various polymorphisms in the thrombotic and thrombolytic cascades and in inflammatory pathways have been investigated in acute coronary syndrome and stroke patients using HCS participants as controls.45–47 Normative reference ranges for the self-administered cognitive assessment tool, the ARCS, have been constructed using the HCS subjects. The ARCS has been validated against formal neuropsychological testing, and compared with other cognitive test batteries, e.g. Consortium to Establish a Registry for Alzheimer's; Disease (CERAD) neuropsychological test battery. The area under the ROC curve (AUC) for the ARCS is excellent for detection of both dementia (AUC = 0.96) and for mild cognitive impairment (AUC = 0.86). The HCS also includes two questions on spirituality, a neglected topic in many cohort studies. Initial analysis of these data indicates that just over half of participants report that spirituality is important in their lives and 24% attend a religious service at least two or three times a month (Table 2). The main strengths of the HCS include: the broad spectrum of simultaneous measures across multiple domains that gives a comprehensive picture of physical and mental health in this older age group; the inclusion of some more unusual measures (mentioned above) and the extensive array of biologicals; the high rate of consent (>90%) to linkage with local, state and national databases; and the strong commitment of participants, due to the strong local focus of the study and community ownership; Early feedback suggests that the study could have been enhanced by including: more measures regarding sleep duration and quality, particularly in view of the emerging relationship between sleep and metabolic syndrome; greater emphasis on estimating falls risk; an ECG, given the importance of atrial fibrillation in this older age group; a means of obtaining information on marginal groups such as those who are non-English speaking; and pet ownership. As with many other cohorts during their inception, the lack of long-term funding remains a source of concern, and survival of the cohort depends on the success of individual project grants targeting specific questions. The chief investigators of the study are W.S., J.A. and C.D.E. and the principal research fellow is M.M., all of whose contact E-mails are provided below. The data have been cleaned by random check of 20% of files as well as error checking using statistical techniques. The hard-copy data files are de-identified and numbered in a sequential order and stored in locked filing cabinets. Biological samples are also de-identified and numbered in the same way and are stored in a secure freezer. Electronic data are stored in a secure statistical analysis system (SAS) file and accessible through the data manager. Inquiries regarding the use of collected data are welcomed and encouraged. All proposals for specific analyses are reviewed by a scientific committee. The University of Newcastle provided $300 000 from its Strategic Initiatives Fund, and $600 000 from the Gladys M Brawn Senior Research Fellowship scheme; Vincent Fairfax Family Foundation, a private philanthropic trust, provided $195 000; The Hunter Medical Research Institute provided media support during the initial recruitment of participants; and Dr Anne Crotty, Prof. Rodney Scott and Associate Prof. Levi provided financial support towards freezing costs for the long-term storage of participant blood samples. The authors would like to thank the men and women participating in the HCS as well as all the staff, investigators and collaborators who have supported or been involved in the project to date. A special thank you should go to Alison Koschel and Debbie Quain who were instrumental in setting up the pilot study and initial phase of the project. Conflict of interest: None declared.

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