Contributions to dementia research by Australian Psychiatry

Research into dementia in the modern era can be said to have begun seriously in 1970 with work on the neuropathology of ‘demented old people’ from Newcastle, United Kingdom. Australian contributions to dementia research followed soon after. In 1973, the Neuropsychiatric Institute in Sydney began a multidisciplinary study of dementia to examine its phenomenology and clinico-pathological correlates and reported on 200 consecutive admissions (Smith and Kiloh, 1981). Interestingly, 6.5% had a reversible cause and 10% were diagnosed as ‘pseudodementia’. As early as 1983, Australian psychiatry had recognised the challenge dementia would pose to society in the future and regarded it as an outstanding opportunity for psychiatry (Henderson, 1983). This predated the identification of β-amyloid as the core protein of the senile plaque, also by Australian researchers and was at a time when dementia was still largely unrecognised.

Other major contributions by Australian psychiatrists have been in the field of epidemiology. Much of the earlier work emanated from the Social Psychiatry Research Unit, established in Canberra in 1975, which later became the National Health and Medical Research Council (NHMRC) Psychiatric Epidemiology Research Centre. This Centre led the development of influential epidemiological studies of dementia including the Hobart Study, the Canberra Longitudinal Study of the Elderly, one of the earliest case-control studies of dementia, and later the Personality & Total Health (PATH) Through Life Study. Salient work continued to emanate from this Centre, and publications that had a lasting impact included the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) (Jorm and Jacomb, 1989) and a meta-analyses of dementia incidence and prevalence. A significant amount of the Centre’s work was published in this journal.

The tradition of analytical epidemiology has continued to the present, with a number of influential longitudinal studies of ageing, which include the Sydney Older Persons’ Study, the Australian Longitudinal Study of Ageing, the Australian Diabetes, Obesity and Lifestyle Study, the Australian Longitudinal Study of Women’s Health, the Blue Mountains Eye Study and the Melbourne Longitudinal Study of Healthy Ageing, among others. More recently, this work has been extended to more detailed studies of cognitive ageing and dementia focusing on early diagnosis and biomarkers, with the establishment of studies such as the Australian Imaging, Biomarkers and Lifestyle Study, the Sydney Memory and Ageing Study, the Older Australian Twins Study, the Sydney Centenarian Study, Prospective Imaging Study of Ageing: Genes, Brain and Behaviour and the Tasmanian Healthy Brain Project. The contributions of these studies are diverse and limitations of space prevent me from going into the details.

Recognising that the indigenous population of Australia is particularly vulnerable to chronic diseases, and has a much lower life expectancy than the Australian of European descent, there has been an effort to identify dementia in the indigenous population and its antecedents through studies such as the Kimberley Indigenous Cohort and the Koori Growing Old Well Study. This work demonstrated that the incidence of dementia in Aboriginal Australians is among the highest in the world and appears to occur at a younger age, thereby posing a challenge for primary prevention in this special population.

The focus of Australian psychiatry has also been on various subtypes of dementia. Vascular dementia is one case in point, with studies such as the Sydney Stroke Study and the North East Melbourne Stroke Incidence Study making salient contributions to the characterisation and risk factor profile of vascular dementia. From this work emerged one of the earlier volumetric quantification of white matter lesions in stroke patients and healthy older people, and evidence for homocysteine as a risk factor for brain atrophy in normal ageing and for small vessel disease. The cognitive profile of vascular dementia that emerged from the Sydney Stroke Study was influential in the new proposed terminology of ‘vascular cognitive disorders’, with a new set of criteria published as the Vascular Behavioural and Cognitive Disorders (VASCOG) criteria (Sachdev et al., 2014).

Australian psychiatrists have been influential in research on treatment and care of dementia. They recognised quite early that dementia imposes a major burden on family and friends who are often the main carers of persons with dementia. Intervening to reduce the level of stress in carers benefits not only the carer but also the quality of care the person with dementia receives (Brodaty and Gresham, 1989). This work led to an international effort to alleviate carer stress and has had a major impact on consumer involvement in dementia services and research. Australia was also one of the first countries to develop a National Dementia Plan, and psychiatrists played an important role in shaping its framework.

Psychiatrists have also been involved in treatment research, ranging from molecular therapies to lifestyle intervention and brain stimulation. One productive area of research, with good translational potential, has been the study of the role metals play in neurodegeneration, and are therefore potent therapeutic targets. One of the first randomised trials to demonstrate that physical exercise could slow the progression of mild cognitive impairment was conducted in Perth, Australia. Another trial from Australia demonstrated the benefit of resistance training in comparison with cognitive training in the Study of Mental and Resistance Training (SMART) trial which investigated both in a 2 × 2 design. Trials to reduce agitation and improve the quality of life of persons with dementia living in residential care, such as the Caring for Aged Dementia Care Resident Study (CADRES) and Sydney Multisite Intervention of LaughterBosses and ElderClowns (SMILE) trials, are another feature of Australian research. Australian psychiatry has also enthusiastically participated in multinational pharmaceutical trials. It was in one such trial that Australian researchers noted the increased risk of stroke in dementia patients being treated with the atypical antipsychotic drug risperidone being used for the management of agitation, leading to a revision of guidelines for treating neuropsychiatric symptoms in dementia internationally. Australian psychiatry has also made significant contributions to the treatment of behavioural and psychiatric symptoms of dementia, which often pose a great burden on the carers of persons with dementia. Another feature of Australian research has been the focus on early diagnosis of dementia in general practice, and dementia now features prominently in the training of medical students and general practitioners.

In conclusion, Australian psychiatry’s contributions to dementia research span epidemiology, phenomenology, diagnosis, treatment and care and the impact of this research has been substantial internationally. The work in analytical epidemiology remains strong and Australia is leading the way in developing international consortia, such as Cohort Studies of Memory in an International Consortium (COSMIC) and STROKOG (Stroke and Cognition Consortium), to examine risk and protective factors for dementia in diverse populations. This work is now extending to multiple modalities of neuroimaging, genomics, epigenomics, proteomics, lipidomics, metabolomics and stem cells and novel treatment studies are being launched, including the world’s largest Internet-based trial to modify lifestyle for the prevention of dementia. The establishment of the NHMRC National institute of Dementia Research in 2014 was a major boost to dementia research in Australia and psychiatry is well placed to take advantage of this development and make a major impact on the ever-increasing burden that dementia places on our society.