Dementia Collaborative Research Centres

This commentary is on the original article by Verity et al. on pages 418–428 of this issue.

1/2900 babies born have one of the over 100 neurodegenerative genetic disorders associated with developing a Childhood Dementia Syndrome. Patients suffering from Childhood Dementia Syndromes usually have normal development initially, before developing symptoms before the age of 18 years old, which progress over years, or potentially even decades.1 Around 90 patients die each year in Australia from a Childhood Dementia. Given the progressive, life-limiting nature of the diagnosis, these patients and their families may receive care in Children’s or Adolescent and Young Adult Hospices, whether for elective respite, complex symptom management or end of life care as well as from community palliative care teams and hospital palliative care consultation services.A Childhood Dementia Initiative report of 2024 noted key issues including a severe lack of knowledge and understanding and a chronic absence of expert care. These then lead to increased parental burden, disempowerment of families, risk to children’s safety and neglect and inequity of care.2This presentation will highlight the role of cross-service care for patients with a Childhood Dementia Syndrome. This includes Dementia Support Australia, Childhood Dementia Initiative, NDIS, Community Specialist Palliative Care team, outpatient specialist medical consultant teams and the specialist multidisciplinary team at the Adolescent and Young Adult Hospice (including clinical psychologist, psychiatrist, occupational therapist, physiotherapist, art and music therapists, speech pathologist, dietitian and bereavement support worker) with a case presentation of a 20 year old with a Childhood Dementia Syndrome.ReferencesElvidge K, Christodoulou J, Farrar M, Tilden D, Maack M, Valeri M, Ellis M, Smith N J C, Childhood Dementia Working Group. The collective burden of childhood dementia: a scoping review. Brain 2023;146:4446–4455Childhood Dementia Initiative 2024. Childhood Dementia: Family experiences of health systems in New South Wales, https://www.childhooddementia.org/getasset/425L8Q March 2024 Sydney Australia.

Abstract BackgroundClinical care for people with dementia as a primary diagnosis, or as a co‐morbidity, can be complex. Physiotherapists play a key role in the care of people living with dementia in multiple settings. The aim of this systematic review was to understand the attitudes, beliefs, knowledge and confidence of physiotherapists and physiotherapy students when working with people living with dementia.MethodsThis was a mixed‐methods systematic review that included qualitative and quantitative studies. Participants were physiotherapists working in any clinical specialty (e.g. gerontology, orthopaedic, neurological), and physiotherapy students who had completed at least 5 weeks of clinical placement. The phenomena of interest were attitudes, beliefs, knowledge and confidence when working with people with dementia in any setting. Eleven databases were searched. Data synthesis followed a convergent integrated approach according to Joanna Briggs Institute methodology for mixed methods systematic reviews.ResultsFifteen studies were included (9 quantitative and 6 qualitative studies). Seven key themes evolved. Five related to the belief that (1) working with people with dementia is complex and challenging; (2) opportunities for education in dementia care are lacking; (3) working with people with dementia is a specialized area of practice; (4) there are unsupportive systems for working with people with dementia; and (5) people with dementia deserve rehabilitation, but their potential to improve is less certain. One theme related to knowledge (lack of knowledge in some areas of dementia care), and one theme related to confidence (lack of confidence in working with people with dementia).Discussion/ConclusionPhysiotherapists and physiotherapy students have low levels of knowledge and confidence in areas including cognition, communication and management of behavioural symptoms. Given that higher levels of knowledge and confidence may be associated with more positive attitudes and beliefs, dementia education needs of physiotherapists at all levels needs to be addressed.

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.

The recognition of dementia as a multifactorial disorder encourages the exploration of new pathways to understand its origins. Social health might play a role in cognitive decline and dementia, but conceptual clarity is lacking and this hinders investigation of associations and mechanisms. The objective is to develop a conceptual framework for social health to advance conceptual clarity in future studies. We use the following steps: underpinning for concept advancement, concept advancement by the development of a conceptual model, and exploration of its potential feasibility. An iterative consensus-based process was used within the international multidisciplinary SHARED project. Underpinning of the concept drew from a synthesis of theoretical, conceptual and epidemiological work, and resulted in a definition of social health as wellbeing that relies on capacities both of the individual and the social environment. Consequently, domains in the conceptual framework are on both the individual (e.g., social participation) and the social environmental levels (e.g., social network). We hypothesize that social health acts as a driver for use of cognitive reserve which can then slow cognitive impairment or maintain cognitive functioning. The feasibility of the conceptual framework is demonstrated in its practical use in identifying and structuring of social health markers within the SHARED project. The conceptual framework provides guidance for future research and facilitates identification of modifiable risk and protective factors, which may in turn shape new avenues for preventive interventions. We highlight the paradigm of social health in dementia as a priority for dementia research.

Disinhibited behaviors in dementia are associated with multiple negative outcomes. However, effective interventions are under-researched. This systematic review aims to provide an overview of intervention studies that report outcome measures of disinhibited behaviors in dementia. Systematic searches of the databases MEDLINE, EMBASE, and PsychINFO, Social Work Abstracts and Cochrane Central Register of Controlled Trial databases were conducted for publications published between 2002 and March 2020. We included hand-searched reviews,original articles, case reports, cohort studies, and randomized controlled trials (RCTs). All studies were rated for research quality. Statistical and clinical significance were considered for individual studies. Effect sizes were included where provided or calculated where possible. Mean effect sizes were calculated for RCTs only. The systematic review included studies involving people living with dementia. The Neuropsychiatric Inventory disinhibition subscale was used most often. Nine pharmacological and 21 nonpharmacological intervention studies utilized different theoretical/clinical approaches. These included pain management, antidepressants, models of care, education and/or training, music-based approaches, and physical activity. The quality of research in RCTs was strong with a greater effect size in nonpharmacological compared to pharmacological approaches (mean Cohen's d = 0.49 and 0.27, respectively). Disinhibition was a secondary outcome in all studies. Pharmacological (including pain management and antidepressants) and, more so, nonpharmacological (models of care, education/training, physical activity, and music) approaches were effective in reducing disinhibition.

Abstract BackgroundMidlife hypertension is a known risk factor for cognitive decline and Alzheimer’s disease but in late life hypertension has been associated variously with better or no different cognition. New research suggests rather than average blood pressure, blood pressure variability best predicts cognitive decline because of excessive flow pulsatility that damages cerebral microcirculation and results in ischaemia.MethodThe Cohort Studies of Memory in an International Consortium (COSMIC) (10 Studies, n=26,227) comprises adults aged 53 – 102 with follow up between 1 and 19.6 years. Cognitive domain scores were aggregated into global cognition scores. Baseline Systolic Blood Pressure (SBP) was analysed categorically (in three groups <120 mmHg, 120 – 139 mmHg, ≥140 mmHg). Visit‐to‐visit SBP variability was captured by variation independent of the mean (VIM). Mixed models were used to examine the association between the parameters at baseline, mean studies mid‐point (3.2 years) and over time with global cognition.ResultSBP groups 120 – 139 mmHg and ≥140 mmHg had significantly worse global cognition at baseline and study midpoint than those with SBP <120 mmHg (Fully adjusted model at baseline, B=‐.148, p=.000 and B=‐.503, p=.000 respectively). There were no between‐group differences in cognitive trajectories over time. There was no significant effect of the antihypertensive use*SBP interaction either at baseline, study midpoint or over time on cognition. Increasing variability was also associated with poorer cognition at study midpoint (B=‐.024, p=.000) but had no effect on cognitive trajectories over time. This effect was reduced but still present when controlling for SBP at baseline (B= ‐.018, p=.000).ConclusionThis study showed that baseline hypertension is associated with poorer cognition at baseline and study midpoint in a dose dependent fashion indicating a likely causative relationship. Interestingly, this relationship was not modified by antihypertensive use, possibly reflecting an inability of late‐life antihypertensive use to reverse hypertensive damage established in mid‐life. This study also showed that blood pressure variability (VIM) is associated with poorer cognition at study mid‐point in a separate but overlapping manner to baseline blood pressure itself. Future blood pressure management guidelines should consider treatment modalities for controlling blood pressure variability as well as mean blood pressure itself.

This study examined the risk of mortality in older adults with newly detected cognitive impairment or dementia. Data from the Australian cohort of the ASPirin in Reducing Events in the Elderly (ASPREE) trial were examined. The ASPREE clinical trial compared daily low-dose aspirin to a placebo and involved 16,703 individuals aged 70 years and over, who were without major cognitive impairment, physical disability, or cardiovascular disease at recruitment. During the trial, evidence of cognitive impairment, based on cognitive testing and medical record information, triggered dementia adjudication of participants using DSM-IV criteria. Cox proportional hazard models were used to compare mortality rates across the dementia, trigger-only, and no-trigger groups. Over a median 4.7-year follow-up period, 806 participants triggered dementia adjudication, with 485 (60.2%) judged to have dementia. Following recruitment, mortality risks were 32.9, 33.6, and 10.8 events per 1000 person-years in the dementia, trigger-no-dementia, and no-trigger groups, respectively. In the fully adjusted model, mortality risks remained higher in the dementia and trigger-no-dementia groups, with hazard ratios of 1.7 (95% CI: 1.3-2.1) and 1.9 (95% CI: 1.5-2.6), respectively. There was no discernible difference between the dementia and trigger-no-dementia groups in mortality rates following recruitment, or following a dementia trigger. These two groups were more likely to die from sepsis, respiratory disease, and dementia, but less likely to die from cancer than the no-trigger group, χ2 =161.5, p < 0.001. ASPREE participants who triggered for a dementia evaluation experienced a substantially higher mortality rate than those who remained cognitively intact. The increase was indistinguishable among persons who met DSM-IV criteria for dementia vs. those who triggered for a dementia evaluation but failed to meet DSM-IV criteria. Future work should investigate whether earlier detection of cognitive decline can be used to identify and prevent early mortality.

Clinical quality registries are increasingly utilised to monitor and improve healthcare quality. Opt-out consent is recommended to maximise participation and ensure validity of data, however, presents specific considerations when including persons with impaired decision-making abilities. This paper describes the innovative Australian Dementia Network Registry recruitment framework designed to optimise inclusion of people with dementia and mild cognitive impairment.