Supporting expression of sexuality by older people with dementia in long-term care from a person-centred care approach.
Dementia causes many changes in people’s lives, including changes to intimate relationships, sex & expression of sexuality. Understanding preferences for expression of sexuality are fundamental in improving physical and sexual health, quality of life and psychosocial well-being for people living with dementia. The project develops and evaluates a tool to improve the care and support of people living with dementia in long-term care settings from a person-centred approach. Knowledge gained from the tool will allow health professionals to extend care provision into a previously neglected area via developing and/or revising guidelines for practice (e.g. care plans and procedures). It implies potential significant improvements in the understanding as well as care practices of health and care professionals towards expression of sexuality so as to enable the facilitation of a care environment that is supportive of the verbalisation and expression of sexual preference, need and desire by people living with dementia.
Investigating the impact of acute muscle injury-induced inflammation on the brain in the elderly.
A serious complication in the elderly following a fall-related injury and hospitalisation is the acute onset of delirium, which can also lead to dementia. This occurs when the body's defences, including the immune system, are in decline. It is now accepted that the immune system plays a key role in injury repair. However, few studies have examined the combined effects of declining immune function on injury repair and whether this impacts brain function. Therefore, in this project we examined changes in the brain of young versus elderly hosts following acute injury. We found a defect in key immune cells, known as macrophages, leads to inflammation and harmful changes in the brain following acute injury in the elderly. Interestingly, blocking macrophages prevented these harmful changes in the brain of elderly hosts following acute injury. Similarly, early intervention with a repurposed anti-ageing therapy reduced in inflammatory changes in the brain. Overall, our data may help to explain the decline in cognitive function observed in the elderly following acute injury and highlights potential therapeutic targets.
Protein Changes that Underlie Selective Vulnerability in Alzheimer’s disease.
The aim of this study was to uncover the protein differences that are responsible for selective vulnerability in Alzheimer’s disease. That is, why some brain regions are more susceptible to the development of neuropathology and neuron death in Alzheimer’s disease than others. This is important because these protein differences may help explain the cause of Alzheimer’s disease and may be new potential drug targets or biomarkers. I used a technique called proteomics to complete the most comprehensive study of the protein differences that are present in regions of the human brain that are selectively vulnerable or resistant in Alzheimer’s disease. I have examined these protein differences in human brain tissue from donors who were at the earliest stages of Alzheimer’s disease including preclinical Alzheimer’s disease and mild cognitive impairment. I also identified the proteins that are selectively enriched in the neuropathological features that define Alzheimer’s disease – amyloid plaques and neurofibrillary tangles. And I have determined which of these proteins directly interact with phosphorylated tau, which is the main protein present in neurofibrillary tangles. Together, my results have identified many new potential drug targets and biomarkers of disease. The most promising of these will be directly examined in future studies which aim to determine how these novel proteins are involved in Alzheimer’s disease.
Making sense of hearing-related neurocognitive impairment: The Auditory Ageing and Cognitive Impairment (AUDACIOUS) Pilot Study.
It is well established that older adults with significant hearing difficulties are more likely to experience cognitive decline and dementia. This link between hearing loss and problems with memory and thinking may be due to communication difficulties, that then lead to withdrawal from activities that are good for maintaining brain health. It is thought that managing hearing loss with hearing aids and other hearing health interventions may reduce a person’s future risk of dementia. However, quality evidence for this is lacking. The Auditory Ageing and Cognitive Impairment Study (AUDACIOUS) will examine the extent to which the relationship between poor hearing and impaired cognitive functioning is explained by lower levels of participation in mentally stimulating activities. It will also investigate if use of hearing rehabilitation services and hearing aids protect against decline. The project findings will have important implications for dementia prevention interventions and practice in hearing health.
Estimating the value of informal care provided to people with dementia in Australia.
While informal carers spend a significant amount of time on caregiving, the time costs of informal care are often neglected in health policy decisions, including funding decisions. Traditionally, informal care hours have been valued using the opportunity cost method (i.e., values informal care by forgone wages) or the replacement cost method (i.e., values informal care at the price of the market substitute). The aim of this study was to use discrete choice experiment (DCE) to estimate the value of informal care provided to people with dementia in Australia. To identify the attributes and attribute levels, a literature review of qualitative studies was undertaken, exploring carers’ positive and negative experiences. Themes identified in the review were further tested for importance and wording in qualitative interviews with carers of people living with dementia. Following two rounds of consultation with an advisory group, the final list of DCE attributes was developed that describe four experiences (i.e., emotional and physical health impacts, relationship with the person receiving care, social and practical support, and doing enjoyable activities), in addition to the attributes ‘hours of care provided’ and the ‘monetary compensation from the government’. Based on results from an online survey that was administered to 700 people, including carers of people with dementia, our findings suggest that respondents were willing to accept a minimum of $21 to provide an additional hour of informal care to a person living with dementia. This cost estimate can inform future economic evaluations and cost-of-illness studies where informal care costs are included.
Getting home safely: Phase 1 - Generating agreement on national policies and procedures for reporting a missing person with dementia.
The aim of this program of research was to make recommendations for a standardised approach to reporting a missing person with dementia in Australia. The study has been conducted in three stages: 1) a review of literature and websites to explore best practice for reporting a missing person with dementia and exploration of current understanding of how to report a missing person; 2) seek lived experience experts and public opinion about the best approach to maintaining safety of people with dementia; 3) confirm that people living with dementia agree with recommendations made. The key findings were: Across the states and territories in Australia, there is not a standardised approach to making a report of a missing person with dementia. However, evidence-based procedures for conducting a search for a missing person with dementia are being practiced by Police; over 50% of health professionals and members of the general public, including care partners of people with dementia, do not know how to report a missing person and believe that they must wait 24 hours before reporting a missing person; key recommendations for improving the safety of a person with dementia include: raising awareness about dementia and the risk of getting lost, long term care facilities should have procedures for monitoring at risk residents and the response to a missing person; staff need to practice the procedure; thorough assessment of risk of getting lost is needed early and at regular intervals; and a public alert system similar to the Amber Alert for children is needed for missing persons with dementia
A cognitive-mobility stress test to detect MCI and risk of conversion to dementia.
An important problem for clinicians is determining who will go on to develop dementia. This will assist with appropriate follow-up and ultimately improved care. Simple measures are required to do this. Walking while performing another task (e.g. dual-task) presents one such measure, as it captures the cognitive contribution to walking. The first step is in seeing if this test distinguishes between no cognitive impairment, mild impairment and dementia.
The aim of this study was to determine if, in people attending a Cognitive Clinic, if a dual-task walking test (walking doing a cognitive task) could distinguish between no diagnosis, mild cognitive impairment and dementia.
In clients attending the clinic (no diagnosis n=11; mild cognitive impairment n=64, dementia n=51) we found that the total cost of walking [gait cost + cognitive cost] while doing a cognitive task differentiated between those with mild cognitive impairment and dementia. Although this supports our hypothesis it appears that findings were mainly driven by the cost to the cognitive rather than the gait task.
There were no differences between those with no diagnosis and mild cognitive impairment or dementia. This may have been due to the small numbers with no diagnosis (n=11), but also the high number of diseases in this group.
In conclusion walking whilst talking may be a simple test to assist with diagnosis of dementia. As this study looked a people at one point in time, future work should determine whether dual task walking can predict those who might develop dementia over time.
Closing the evidence-practice gap in young onset dementia care: a pilot implementation trial.
Our research is the first to examine the experiences of young people with dementia and their family members since they became eligible for the National Disability Insurance Scheme in 2016. We found that although people living with Younger Onset Dementia (YOD) and their families feel strongly that they belong in the NDIS rather than the aged care system, they continue to face barriers to accessing the support they need in this new system. Most importantly, disability professionals lack experience and expertise with dementia care and this limits the availability of suitable services. We went on to test out a multi-component online strategy aiming to improve the skills of professionals working with people living with YOD and encourage aged and disability care professionals to work together cohesively. While the strategy was successful at improving collaboration and skills, our participants found it difficult to implement improvements to their services if their organisation was not supportive of the changes. The rich data provided by our participants will allow us to refine the strategy ready for trial on a wider scale, with a focus on professionals who are senior enough in their organisation to enact meaningful change.
Spatial convergence of dementia and cardiovascular disease risk: evidence to inform policy and practice.
Delivery of more effective preventive intervention efforts to reduce and delay onset of dementia and cardiovascular disease (CVD) events requires knowing where high levels of convergence of dementia and CVD risks occur in communities.
We calculated dementia risk scores for people aged 65 and over and identify people who have higher risk of developing dementia using GP clinical data from Adelaide. The estimated future risk of dementia will help to identify high risk individual and screening for early diagnosis of dementia in primary care setting. Further, this provides an opportunity to general practitioners to monitor risk factors for their patients and reduce or delay the risk of developing dementia.
We visualised the pattern of dementia risk score across communities to identify areas with greater risk of dementia. This allowed us to investigate the potential association between built environment factors and the pattern of community level dementia risk. We investigated air pollutions, public open green space, walkability and social fragmentation effects on dementia. Our result showed that there is an association between air pollution (level of NO2), social fragmentation and walkability index.
We found a significant relationship between social fragmentation (mobility component) and estimated dementia risk. This suggest that social inclusion and social cohesion measured as ‘neighbourhood’s social environment structure’ may be associated with reduced risk of dementia.
We found that an increased proportion of public open spaces within a SA1 was associated with a decrease in estimated risk of dementia. It is plausible that exposure to public open spaces may increase physical activity, leading to a protective effect for dementia risk
Perminder Sachdev AM
Nanotechnology for the diagnosis and treatment of neurodegenerative disorders.
There is currently no treatment to prevent or modify the course of Alzheimer’s disease (AD) and other neurodegenerative dementias. Delivering drugs across the blood-brain barrier has been a major challenge in many neurodegenerative conditions, including Alzherimer's disease. However, nanotechnology, which is a science based on manipulating matter at the nanoscale, may offer a solution. Using the latest developments in nanoscience, this project aimed to overcome two such obstacles – diagnosis and drug delivery. Using nanotechnology, key findings from this project were; 1) successful attachment of specialised ‘treatment’ molecules to nanoparticles, which crossed the blood-brain barrier in mice, 2) 'treatment' molecules detected and bound to Alzheimer’s disease plaques in mice brain and 3) MRI of the mice brains was able to detect these nanoparticles and diseased plaques. These findings will help to uncover new pathways for diagnosis via MRI and the development of effective treatments for Alzheimer’s disease.
The importance of blood pressure and its variability to dementia: an individual participant data meta-analysis from the VARIABLE BRAIN consortium.
The brain requires a continual supply of oxygen via regulatory mechanisms that ensure a constant blood flow and pressure. High blood pressure, such as that measured by a GP, is related to the risk of developing dementia. Yet blood pressure can fluctuate up and down when sitting, standing, sleeping, and exercising, and some changes may also occur over time (days, weeks, months, years). We were interested in how these fluctuations in a person’s blood pressure were associated with brain functioning either as a diagnosis of dementia or cognitive impairment.
We looked at 20 different studies who measured blood pressure change and diagnosis of dementia or cognitive impairment. By analyzing data from more than 7 million persons (7,899,697) we found that fluctuation or variability in blood pressure was associated with dementia or cognitive impairment. In fact, we found that this variation in blood pressure was more strongly associated with dementia and cognitive impairment than was a person’s average blood pressure. In other words, the ups and downs of a person’s blood pressure over time might be more important to assess the risk of developing dementia or cognitive impairment than the average blood pressure
Investigating how presenilin causes neurodegeneration in Alzheimer’s disease.
There are some people who get an inherited form of Alzheimer’s disease because of errors in certain genes. The reason for this is not certain. Using brain cells that are grown in a dish, we have made them express these genes containing errors. We have shown that these genes impact on vulnerability for a certain type of cellular death. These discoveries introduce new possibilities for therapies to treat Alzheimer’s disease.
An international common data model for improving medicine management for people with dementia and comorbid conditions.
Although dementia disproportionately impacts global disease burden, people with dementia are usually not included in key clinical trials to provide evidence of medication efficacy and safety. With the ‘Four Continents For Dementia’ (4C4D) initiative, we aim to provide new evidence to inform prescribing for people with dementia.
We have shown that people with dementia have similar responses to different dual blood pressure treatments compared to people without dementia. Our results give reassurance to prescribers when choosing the effective treatment combinations to prevent cardiovascular events and improve survival in people with dementia. We also found that people with diabetes and dementia will equally benefit from newer, so called SGLT2 inhibitor medications or “gliflozins” for type 2 diabetes, which have previously shown to reduce the risk of heart disease and hospital visits due to heart failure. We have now demonstrated that similar benefits occur in people with dementia. However, other newer diabetes medications, so called DPP4 inhibitors or “gliptins” are no necessary advantageous in preventing cardiovascular events than older diabetes medications, but they may be better in improving survival.
When studying preferences of prescribers, carers and people living with dementia for ceasing a blood pressure medication, people living with dementia considered important that pill burden was lower after the cessation. However, carers of people living with dementia and prescribers would not cease blood pressure medication to lower pill burden. Overall, out study highlighted that all three groups valued different attributes when considering whether or not to cease blood pressure medication. This emphasises the importance of shared decision-making within the deprescribing process.
Ensuring safe and appropriate hospital discharge prescribing of opioids for people living with dementia.
Pain is a common symptom among people living with dementia. Opioid analgesics are often prescribed for pain at hospital discharge. This study aims to investigate opioid prescriptions on hospital discharge and the risk of rehospitalisation and death in people living with dementia. This study used four Victorian datasets to create one comprehensive dataset, which included 14,212 people ≥65 years admitted to hospital between 2015-2018 of which 2,048 have a diagnosis of dementia. Findings relating to people living with dementia who were prescribed an opioid analgesic at hospital discharge were:
- Opioid prescription on hospital discharge, is associated with a higher chance of death or being readmitted to hospital within 28 days (compared to those not prescribed an opioid)
- Most types of opioids may increase the chance of rehospitalisation or death in people with dementia, but some medications may pose a higher risk (for example fentanyl was found to have the highest risk)
- Opioid prescription may be associated with a higher risk of death or rehospitalisation in people with dementia when prescribed on an ad hoc basis (i.e. taken when in pain only), compared to when prescribed on a regular basis. This is in contradiction to current recommendations for opioid prescribing. It is recommended further research is completed to confirm this.
- Opioid prescription may increase the risk of hospital admission with a possible side effect of the opioid, in particular sedation or drowsiness.
In addition to the above work, a scoping review of the published research studies was undertaken which found that people living with dementia are more prone to developing side effects of opioids, with a likelihood that opioid prescription is associated with falls and fractures and behavioural side effects such as confusion. This indicates that further research is required, to improve guidelines for opioid prescription and thus better health outcomes for people living with dementia.
Financial vulnerabilities in younger onset dementia: insights for targeted interventions.
People with dementia have a higher risk of being financially exploited, and may also have difficulty managing their money. Despite serious consequences, little is known about the prevalence and causes of financial vulnerabilities in these individuals, and how this impacts on their families. Currently, financial skills are not commonly assessed following a diagnosis of dementia. Therefore, it is unclear which types of skills are affected, and whether some skills are affected more in certain forms of dementia. One reason for the lack of financial skills assessment is the lack of appropriate tests available to clinicians.
Through this project, a new test of financial skills for individuals with dementia was developed. The test assesses a wide range of financial skills that are relevant for everyday life, including handling cash, paying bills, budgeting, scam detection, financial judgment and goal-setting and understanding financial management responsibilities (e.g. power of attorney). This new test will provide insights into the types of financial difficulties experienced by people with dementia, and help determine appropriate ways to intervene and manage these difficulties.
Yen Ying Lim
High-frequency sampling of cognition in clinically normal adults at genetic risk of Alzheimer’s disease using mobile applications.
Previous research using the Online Repeatable Cognitive Assessment Language Learning Test (ORCA-LLT) has demonstrated its utility in detecting differences in learning between groups of cognitively normal older adults who had abnormal levels of the beta-amyloid protein and cognitively normal older adults with normal levels of beta-amyloid. These changes can be detected using the ORCA battery in a much shorter period of time than existing screening tools. This led to the hypothesis that deficits in learning may be one of the earliest cognitive abnormalities of Alzheimer’s disease.
We have now challenged this even further by examining rates of learning in cognitively normal, amyloid negative individuals who are APOE ε4 carriers and non-carriers. Using the ORCA-LLT, we found that even those who are amyloid negative, ε4 carriers showed a substantially lower rate of learning that matched ε4 non-carriers. These results provide the first evidence that subtle cognitive abnormalities can be detected even prior to individuals reaching accepted thresholds of amyloid abnormality.
We hope to use these high frequency modes of cognitive testing to detect extremely subtle signs of memory and thinking changes in a much shorter amount of time in individuals who have an elevated risk for Alzheimer's disease dementia than can be detected using standard paper and pencil neuropsychological assessments.
The influence of cerebrovascular disease in dementia with Lewy bodies.
Dementia with Lewy bodies is a common form of neurodegenerative dementia, but despite this, has been less researched and is less understood than other dementia types. In some people living with dementia, certain brain changes that are caused by brain vessel disease are more common. Some examples of these changes are tiny strokes or small bleeds in the brain called microbleeds. These can usually be seen on MRI scans of the brain, but their significance in dementia is uncertain.
The initial part of the study involved a systematic search for all published studies on brain vessel diseases in Dementia with Lewy bodies. Studies suggested that some changes relating to brain vessel diseases (tiny infarcts, microbleeds and areas of increased brightness on MRI, called white matter hyperintensities) appear to be more common in people with Dementia with Lewy bodies.
The second part of the project involved studying MRI brain changes in 22 people living with Dementia with Lewy bodies who participated in the study. In participants with Dementia with Lewy bodies, microbleeds were seen on the MRI brain scans in 14%. The location of the microbleeds in these participants suggested that they may be a result of certain contributing disease processes, such as Alzheimer’s disease.
This research provides a framework for further studies on these brain changes, including why they may be more prevalent in Dementia with Lewy bodies and what effects they may have in people with Dementia with Lewy bodies.
Protecting axon-glial interactions to guard against dementia
Alzheimer’s disease and vascular dementia can be associated with vascular related brain damage, often caused by brain cells being deprived of oxygen. White matter regions of the brain are particularly susceptible to this type of injury. They contain the long, thin nerve cell processes that act like the electrical wires of the brain, and the specialist insulating cells called oligodendrocytes, that wrap and insulate the nerves, and provide them with energy and nutrients. This project will study the interactions between nerve cells and oligodendrocytes under normal and low oxygen conditions. It will determine how oligodendrocytes die and determine whether blocking this pathway to enhance oligodendrocyte survival can improve nerve cell health in low oxygen conditions. Additionally, this project will examine individual oligodendrocytes in order to understand which nerves they associate with, how they regulate nerve cell function to facilitate learning and memory, and how this is affected in dementia.
How does stress impact pathological processes in Alzheimer's disease?
Brain changes associated with stress may increase risk for Alzheimer’s disease, or make it worse. This makes the stress hormone system an exciting target for new drugs, but more work is required to understand how such drugs might work. This study will investigate how the stress hormone system impacts production and accumulation of a molecule, amyloid beta, which builds up abnormally in brain cells during Alzheimer’s disease. This study will also determine whether this happens ‘vice versa’, so that amyloid beta abnormalities change the sensitivity of brain cells to stress. By performing these experiments, we hope to lay the groundwork for new therapies for reducing risk for Alzheimer’s disease and slowing its progression.
Entrainment of brain oscillations to improve inhibitory function in people with MCI
Inhibitory control, a key aspect of executive cognitive control, declines early in the neurodegenerative processes that ultimately lead to dementia. It appears that changes in the brain networks are responsible for a decline in inhibitory control in individuals with mild cognitive impairment (MCI), a preclinical stage of dementia. It has been suggested that non-invasive brain stimulation (NiBS) is a powerful tool to improve cognitive function in people with the AD. Here we will investigate whether the application of NiBS can improve inhibitory function in people with MCI. The aims of the project are (1) to investigate the efficacy of NiBS on inhibitory function in people with MCI, and (2) to reveal the underlying neurophysiological mechanisms in inhibitory processing changes induced by NiBS on brain networks. Thus, the project will answer the question of whether NiBS can ameliorate declines in inhibitory control by altering the functioning of specific brain networks.