The Impact of Misaligned Perceived and Objective Fall Risk in Cognitively Impaired Older People.

Background: Cognitive impairment (CI) may impair the ability to accurately perceive physical capacity and fall risk. Objective: We investigated perceived (measured as concern about falls) and physiological fall risk in community-dwelling older people with CI, the characteristics of the aligned and misaligned groups and the impact of misaligned perceptions on falls. Methods: Participants (n= 293) with mild-moderate CI were classified into four groups based on validated physiological and perceived fall risk assessments: 1) vigorous: low perceived and physiological fall risk; 2) anxious: high perceived and low physiological fall risk; 3) unaware: low perceived and high physiological fall risk; and 4) aware: high perceived and physiological fall risk. Groups were compared with respect to neuropsychological and physical function, activity and quality of life measures, and prospective falls (12-months). Results: The anxious (IRR = 1.70, 95% CI = 1.02-2.84), unaware (IRR = 2.00, 95% CI = 1.22-3.26), and aware (IRR = 2.53, 95% CI = 1.67-3.84) groups had significantly higher fall rates than the vigorous group but fall rates did not significantly differ among these groups. Compared with the vigorous group: the anxious group had higher depression scores and reduced mobility and quality of life; the unaware group had poorer global cognition, executive function and mobility and lower physical activity levels; and the aware group had an increased prevalence of multiple physical and cognitive fall risk factors. Conclusions: Fall rates were increased in participants who had increased perceived and/or physiological fall risk. Contrasting fall risk patterns were evident in those who under- and over-estimated their fall risk. Understanding these characteristics will help guide fall risk assessment and prevention strategies in community-dwelling older people with CI.

Incidence of fragility hip fracture across the Asia-pacific region: A systematic review.

PURPOSE: This systematic review aimed to update fragility hip fracture incidences in the Asia Pacific, and compare rates between countries/regions. METHOD: A systematic search was conducted in four electronic databases. Studies reporting data between 2010 and 2023 on the geographical incidences of hip fractures in individuals aged ≥50 were included. Exclusion criteria were studies reporting solely on high-trauma, atypical, or periprosthetic fractures. We calculated the crude incidence, age- and sex-standardised incidence, and the female-to-male ratio. The systematic review was registered with PROSPERO (CRD42020162518). RESULTS: Thirty-eight studies were included across nine countries/regions (out of 41 countries/regions). The crude hip fracture incidence ranged from 89 to 341 per 100,000 people aged ≥50, with the highest observed in Australia, Taiwan, and Japan. Age- and sex-standardised rates ranged between 90 and 318 per 100,000 population and were highest in Korea and Japan. Temporal decreases in standardised rates were observed in Korea, China, and Japan. The female-to-male ratio was highest in Japan and lowest in China. CONCLUSION: Fragility hip fracture incidence varied substantially within the Asia-Pacific region. This observation may reflect actual incidence differences or stem from varying research methods and healthcare recording systems. Future research should use consistent measurement approaches to enhance international comparisons and service planning.

Variation in care and outcomes for people after hip fracture with and without cognitive impairment; results from the Australian and New Zealand Hip Fracture Registry.

BACKGROUND: People with dementia have poorer outcomes after hip fracture and this may be due in part to variation in care. We aimed to compare care and outcomes for people with and without cognitive impairment after hip fracture. METHODS: Retrospective cohort study using Australian and New Zealand Hip Fracture Registry data for people ≥50 years of age who underwent hip fracture surgery (n = 49,063). Cognitive impairment or known dementia and cognitively healthy groups were defined using preadmission cognitive status. Descriptive statistics and multivariable mixed effects models were used to compare groups. RESULTS: In general, cognitively impaired people had worse care and outcomes compared to cognitively healthy older people. A lower proportion of the cognitively impaired group had timely pain assessment (≤30 min of presentation: 61% vs 68%; p < 0.0001), were given the opportunity to mobilise (89% vs 93%; p < 0.0001) and achieved day-1 mobility (34% vs 58%; p < 0.0001) than the cognitively healthy group. A higher proportion of the cognitively impaired group had delayed pain management (>30 mins of presentation: 26% vs 20%; p < 0.0001), were malnourished (27% vs 15%; p < 0.0001), had delirium (44% vs 13%; p < 0.0001) and developed a new pressure injury (4% vs 3%; p < 0.0001) than the cognitively healthy group. Fewer of the cognitively impaired group received rehabilitation (35% vs 64%; p < 0.0001), particularly patients from RACFs (16% vs 39%; p < 0.0001) and were prescribed bone protection medication on discharge (24% vs 27%; p < 0.0001). Significantly more of the cognitively impaired group had a new transfer to residential care (46% vs 11% from private residence; p < 0.0001) and died at 30-days (7% vs 3% from private residence; 15% vs 10% from RACF; both p < 0.0001). In multivariable models adjusting for covariates with facility as the random effect, the cognitively impaired group had a greater odds of being malnourished, not achieving day-1 walking, having delirium in the week after surgery, dying within 30 days, and in those from private residences, having a new transfer to a residential care facility than the cognitively healthy group. CONCLUSIONS: We have identified several aspects of care that could be improved for patients with cognitive impairment - management of pain, mobility, nutrition and bone health, as well as delirium assessment, prevention and management strategies and access to rehabilitation. Further research is needed to determine whether improvements in care will reduce hospital complications and improve outcomes for people with dementia after hip fracture.

Effect of cognitive training on cognitive function in community-dwelling older people with mild-to-moderate dementia: A single-blind randomised controlled trial.

OBJECTIVES: The purpose of this assessor-blinded, randomised controlled trial was to determine the effect of computerised cognitive training (CT) on executive function, processing speed and working memory in 61 people with mild-to-moderate dementia. METHODS: The primary outcomes were forward Digit Span and Trail Making Tests (TMT) at the completion of the 6-month intervention. Secondary outcomes included cognitive and physical performance, rate of falls, participant and caregiver's quality of life and usability and adherence to the CT program. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12617000364370). RESULTS: Intervention group (n = 31) participants averaged 81 min of CT per week, and system usability scores were acceptable (participants: 68.8 ± 22.1; caregivers: 79.4 ± 23.5). There were no statistically significant differences in cognitive or physical performance outcomes between the intervention and control groups at 6- or 12-months (between-group differences [95% CI] for primary outcomes at 6-months: Forward Digit Span -0.3 [-0.8, 0.3]; TMT-A 2.7 s [-14.1, 19.5]; TMT-B -17.1 s [-79.3, 45.2]). At the 12-month follow-up reassessment, the intervention group reported significantly more depressive symptoms and had lower caregiver-rated participant quality of life and higher caregiver quality of life compared to control. CONCLUSIONS: This study showed no benefit of the CT program on working memory, processing speed and executive function. Future studies are required to better understand how CT can be used to improve cognitive and physical functioning in older people with mild-moderate dementia.

Improving hip fracture care: A five-year review of the early contributors to the Australian and New Zealand Hip Fracture Registry.

OBJECTIVE: The aim of this study was to examine temporal trends (2016-2020) in hip fracture care in Australian and New Zealand (ANZ) hospitals that started providing patient-level data to the ANZ Hip Fracture Registry (ANZHFR) on/before 1 January 2016 (early contributors). METHODS: Retrospective cohort study of early contributor hospitals (n = 24) to the ANZHFR. The study cohort included patients aged ≥50 years admitted with a low trauma hip fracture between 1 January 2016 and 31 December 2020 (n = 26,937). Annual performance against 11 quality indicators and 30- and 365-day mortality were examined. RESULTS: Compared to 2016/2017, year-on-year improvements were demonstrated for preoperative cognitive assessment (2020: OR 3.57, 95% confidence interval [95% CI] 3.29-3.87) and nerve block use prior to surgery (2020: OR 4.62, 95% CI 4.17-5.11). Less consistent improvements over time from 2016/2017 were demonstrated for emergency department (ED) stay of <4 h (2017; 2020), pain assessment ≤30 min of ED presentation (2020), surgery ≤48 h (2020) and bone protection medication prescribed on discharge (2017-2020; 2020 OR 2.22, 95% CI 2.03-2.42). The odds of sustaining a hospital-acquired pressure injury increased in 2019-2020 compared to 2016. The odds of receiving an orthogeriatric model of care and being offered the opportunity to mobilise on Day 1 following surgery fluctuated. There was a reduction in 365-day mortality in 2020 compared to 2016 (OR 0.86, 95% CI 0.74-0.98), whereas 30-day mortality did not change. CONCLUSIONS: Several quality indicators improved over time in early contributor hospitals. Indicators that did not improve may be targets for future care improvement activities, including considering incentivised hip fracture care, which has previously been shown to improve care/outcomes. COVID-19 and reporting practices may have impacted the study findings.

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.

BACKGROUND: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. OBJECTIVES: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. METHODS: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. RESULTS: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. CONCLUSIONS: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cognitive and physical declines and falls in older people with and without mild cognitive impairment: a 7-year longitudinal study.

OBJECTIVES: We examined longitudinal changes in cognitive and physical function and associations between change in function and falls in people with and without mild cognitive impairment (MCI). DESIGN: Prospective cohort study with assessments every 2 years (for up to 6 years). SETTING: Community, Sydney, Australia. PARTICIPANTS: Four hundred and eighty one people were classified into three groups: those with MCI at baseline and MCI or dementia at follow-up assessments (n = 92); those who fluctuated between cognitively normal and MCI throughout follow-up (cognitively fluctuating) (n = 157), and those who were cognitively normal at baseline and all reassessments (n = 232). MEASUREMENTS: Cognitive and physical function measured over 2-6 years follow-up. Falls in the year following participants' final assessment. RESULTS: In summary, 27.4%, 38.5%, and 34.1% of participants completed 2, 4, and 6 years follow-up of cognitive and physical performance, respectively. The MCI and cognitive fluctuating groups demonstrated cognitive decline, whereas the cognitively normal group did not. The MCI group had worse physical function than the cognitively normal group at baseline but decline over time in physical performance was similar across all groups. Decline in global cognitive function and sensorimotor performance were associated with multiple falls in the cognitively normal group and decline in mobility (timed-up-and-go test) was associated with multiple falls across the whole sample. CONCLUSIONS: Cognitive declines were not associated with falls in people with MCI and fluctuating cognition. Declines in physical function were similar between groups and decline in mobility was associated with falls in the whole sample. As exercise has multiple health benefits including maintaining physical function, it should be recommended for all older people. Programs aimed at mitigating cognitive decline should be encouraged in people with MCI.

Candidate genes for field resistance to cassava brown streak disease revealed through the analysis of multiple data sources.

Cassava (Manihot esculenta Crantz) is a food and industrial storage root crop with substantial potential to contribute to managing risk associated with climate change due to its inherent resilience and in providing a biodegradable option in manufacturing. In Africa, cassava production is challenged by two viral diseases, cassava brown streak disease (CBSD) and cassava mosaic disease. Here we detect quantitative trait loci (QTL) associated with CBSD in a biparental mapping population of a Tanzanian landrace, Nachinyaya and AR37-80, phenotyped in two locations over three years. The purpose was to use the information to ultimately facilitate either marker-assisted selection or adjust weightings in genomic selection to increase the efficiency of breeding. Results from this study were considered in relation to those from four other biparental populations, of similar genetic backgrounds, that were phenotyped and genotyped simultaneously. Further, we investigated the co-localization of QTL for CBSD resistance across populations and the genetic relationships of parents based on whole genome sequence information. Two QTL on chromosome 4 for resistance to CBSD foliar symptoms and one on each of chromosomes 11 and 18 for root necrosis were of interest. Of significance within the candidate genes underlying the QTL on chromosome 4 are Phenylalanine ammonia-lyase (PAL) and Cinnamoyl-CoA reductase (CCR) genes and three PEPR1-related kinases associated with the lignin pathway. In addition, a CCR gene was also underlying the root necrosis-resistant QTL on chromosome 11. Upregulation of key genes in the cassava lignification pathway from an earlier transcriptome study, including PAL and CCR, in a CBSD-resistant landrace compared to a susceptible landrace suggests a higher level of basal lignin deposition in the CBSD-resistant landrace. Earlier RNAscope® in situ hybridisation imaging experiments demonstrate that cassava brown streak virus (CBSV) is restricted to phloem vessels in CBSV-resistant varieties, and phloem unloading for replication in mesophyll cells is prevented. The results provide evidence for the involvement of the lignin pathway. In addition, five eukaryotic initiation factor (eIF) genes associated with plant virus resistance were found within the priority QTL regions.

Associations between psychotropic and anti-dementia medication use and falls in community-dwelling older adults with cognitive impairment.

OBJECTIVES: Evidence for effective fall prevention strategies is limited for people with cognitive impairment. Understanding what factors contribute to fall risk identifies potential intervention strategies. We aimed to determine if psychotropic and anti-dementia medication use are associated with falls in community-dwelling older people with mild-moderate cognitive impairment and dementia. DESIGN: Secondary analysis of an RCT (i-FOCIS). PARTICIPANTS AND SETTING: 309 community-dwelling people with mild to moderate cognitive impairment or dementia from Sydney, Australia. METHODS: Demographic information, medical history, and medication use were collected at baseline and participants were followed up for 1-year for falls using monthly calendars and ancillary telephone falls. RESULTS: Psychotropic medication use was associated with an increased rate of falls (IRR 1.41, 95%CI 1.03, 1.93) and slower gait speed, poor balance and reduced lower limb function when adjusting for age, sex, education and cognition, as well as RCT group allocation when examining prospective falls. Antidepressants use increased the rate of falls in a similarly adjusted model (IRR 1.54, 95%CI 1.10, 2.15), but when additionally adjusting for depressive symptoms, antidepressant use was no longer significantly associated with falls while depressive symptoms was. Anti-dementia medication use was not associated with rate of falls. CONCLUSIONS: Psychotropic medication use increases fall risk, and anti-dementia medication does not reduce fall risk in older adults with cognitive impairment. Effective management of depressive symptoms, potentially with non-pharmacological approaches, is needed to prevent falls in this population. Research is also required to ascertain the risks/benefits of withdrawing psychotropic medications, particularly in relation to depressive symptoms.

Risk factors for falls in community-dwelling older people with mild cognitive impairment: a prospective one-year study.

Objective: Mild cognitive impairment (MCI) is considered an intermediate stage between normal cognitive function and dementia. Fall risk is increased in this group, but there is limited literature exploring specific fall risk factors that may be addressed in fall prevention strategies. The aim of this study was to examine risk factors for falls in older people with MCI, focusing on cognitive, psychological and physical factors. Methods: Participants (n = 266, 45% women) were community-dwelling older people aged 70-90 years who met the criteria for MCI. Cognitive, psychological, sensorimotor and physical assessments, physical activity levels, medication use, general health and disability were ascertained at baseline. Falls were monitored prospectively for 12 months. Results: During follow-up, 106 (40%) participants reported one or more falls. Poorer visual contrast sensitivity, increased postural sway, lower levels of weekly walking activity, higher levels of depressive symptoms and psychotropic medication use were significantly associated with faller status (≥1 falls) in univariable analyses. Of these factors, poor visual contrast sensitivity, increased postural sway and psychotropic medication use were found to be significant independent predictors of falls in multivariable analysis while controlling for age and sex. No measures of cognitive function were associated with falls. Conclusions: Poor visual contrast sensitivity, impaired balance and psychotropic medication use predicted falls in community-dwelling people with MCI. These risk factors may be amenable to intervention, so these factors could be carefully considered in fall prevention programs for this population.

Sunbeam Program Reduces Rate of Falls in Long-Term Care Residents With Mild to Moderate Cognitive Impairment or Dementia: Subgroup Analysis of a Cluster Randomized Controlled Trial.

OBJECTIVES: The Sunbeam trial significantly reduced falls in long-term aged care (LTC) residents. The current study's primary objective was to undertake subgroup analysis of the Sunbeam trial, to determine whether the intervention was effective for reducing falls in LTC residents with mild-moderate cognitive impairment/dementia. Secondary objectives were to determine intervention effects on cognitive and physical function. DESIGN: Subgroup analysis of a cluster randomized controlled trial (RCT). SETTING AND PARTICIPANTS: Permanent residents of LTC in Australia who participated in the Sunbeam trial with Addenbrooke's Cognitive Examination-Revised (ACE-R) scores <83 (Mini-Mental State Examination >14 = main trial inclusion criteria). METHODS: Of 221 participants, 148 had an ACE-R <83 and were included in this study. Sixteen LTC residences (clusters) were randomized to receive either the Sunbeam program or usual care. The Sunbeam program involved two 1-hour sessions/week of tailored and progressive resistance and balance training for 25 weeks followed by a maintenance program (two 30-min sessions/week of nonprogressive exercise for 6 months). Assessments were conducted at baseline, 6 months, and 12 months. Falls were recorded using routinely collected data from the LTC incident management systems. RESULTS: Rate of falls (50%) and risk of falls (31%), multiple falls (40%), and injurious falls (44%) were reduced in the intervention group. The intervention group had significantly better balance (static and dynamic) and sit-to-stand ability when compared with the control group at 6 months and significantly better dynamic balance at 12 months. There were no serious adverse events. CONCLUSIONS AND IMPLICATIONS: The Sunbeam Program significantly reduced falls and improved physical performance in cognitively impaired LTC residents. This is a novel and important finding, as many previous studies have excluded people with cognitive impairment/dementia and inconsistent findings have been reported when this population has been studied. Our findings suggest that progressive resistance and balance exercise is a safe and effective fall prevention intervention in LTC residents with mild-moderate cognitive impairment/dementia.

The association between white matter hyperintensity volume and cognitive/physical decline in older people with dementia: A one-year longitudinal study.

OBJECTIVES: Understanding the relationship between white matter hyperintensities (WMHs) and cognitive and physical decline in people with dementia will assist in determining potential treatment strategies. Currently there is conflicting evidence describing the association between WMHs and cognitive decline and, WMHs association with declines in objective measures of physical function have not been examined. We examined the relationship between baseline WMH volume and physical/cognitive decline over one-year in older people with dementia. METHODS: Twenty-six community-dwelling older people with dementia (mean age = 81 ± 8 years; 35% female) were assessed at baseline and follow-up (one-year) using the Addenbrooke's Cognitive Examination-Revised (including verbal fluency), Trail Making Test A, the Physiological Profile Assessment (PPA), timed-up-and-go (TUG) and gait speed. WMH volumes were quantified using a fully automated segmentation toolbox, UBO Detector. RESULTS: In analyses adjusted for baseline performance, higher baseline WMH volume was associated with decline in executive function (verbal fluency), sensorimotor function (PPA) and mobility (TUG). Executive function (semantic/category fluency) was the only domain association that withstood adjustment for age, and additionally hippocampal volume. CONCLUSIONS: In unadjusted analyses, WMH volume was associated with one-year declines in cognitive and physical function in older people with dementia. The association with executive function decline withstood adjustment for age. More research is needed to confirm these findings and explore whether vascular risk reduction strategies can reduce WMH volume and associated cognitive and physical impairments in this group.

Relationship between Depressive Symptoms and Cognitive, Psychological, and Physical Performance in Community-Dwelling Older People with Cognitive Impairment.

INTRODUCTION: Dementia and depression often coexist. Understanding how concomitant comorbidities affect function can improve assessment and management strategies. We examined the relationship between cognitive, psychological, and physical function and depressive symptoms in people with cognitive impairment. METHODS: Cross-sectional study using baseline data from the iFOCIS randomized controlled trial involving 309 participants with mild-moderate cognitive impairment. The association between cognitive (Addenbrooke's Cognitive Examination-III [ACE-III], Frontal Assessment Battery), psychological (Goldberg Anxiety Scale; Iconographical Falls Efficacy Scale), and physical (Physiological Profile Assessment; Short Physical Performance Battery [SPPB]) function, and quality of life (QoL), physical activity levels and activities of daily living, and depressive symptoms (15-item Geriatric Depression Scale [GDS]) were assessed (adjusted for age, sex, education, and ACE-III as appropriate). RESULTS: Participants with depressive symptoms (GDS ≥4) had significantly more falls in the previous year and a higher number of comorbidities than people without depressive symptoms (GDS <4). Each point increase in the GDS was associated with better memory, higher levels of anxiety and concern about falling, poorer balance, slower gait speed, and reduced QoL. The relationship between the GDS and poor balance and QoL withstood additional adjustment for comorbidity tertiles. The relationship between GDS and concern about falls withstood additional adjustment for previous falls (12 months) and SPPB scores. CONCLUSIONS: Depressive symptomatology is associated with poorer physical and psychological function and reduced QoL in people with cognitive impairment. These factors should be considered when assessing and intervening in this group. Future research could examine these relationships longitudinally to establish causality and examine intervention efficacy in this group.

Risk factors for falls in older people with cognitive impairment living in the community: Systematic review and meta-analysis.

PURPOSE: This systematic review aimed to identify risk factors for prospectively ascertained falls, focusing on those that are potentially modifiable (physical and neuropsychological factors), in older people with cognitive impairment living in the community. RESULTS: A comprehensive search of five databases identified 16 high quality (Newcastle-Ottawa Scale ≥8/9) relevant articles. Meta-analyses were undertaken for five potential fall risk factors. Of these, fallers had significantly poorer balance (standardized mean difference = 0.62, 95 %CI 0.45, 0.79) with low heterogeneity. Global cognition was not significantly associated with faller status in a meta-analysis with low heterogeneity. Meta-analyses of mobility (Timed Up-and-Go), gait speed and depressive symptoms had high heterogeneity and were not statistically significant or were borderline significant (p = 0.05). Sensitivity analyses (removing one study sample's results that differed markedly from the other included samples) reduced heterogeneity to 0% and revealed fallers had significantly poorer mobility and more depressive symptoms than non-fallers. Fallers also walked significantly slower, but heterogeneity remained high. CONCLUSIONS: In older people with cognitive impairment, fallers presented with balance deficits, poor mobility, slow gait speed and depressive symptoms. Reduced global cognition was not associated with falls. These findings suggest that interventions should target balance impairment and reveal that more high-quality research is needed.

Implementation of the StandingTall programme to prevent falls in older people: a process evaluation protocol.

INTRODUCTION: One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. METHODS AND ANALYSIS: This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. TRIAL REGISTRATION NUMBER: ACTRN12619001329156.

The association between white matter hyperintensity volume and gait performance under single and dual task conditions in older people with dementia: A cross-sectional study.

BACKGROUND: Understanding the relationship between white matter hyperintensities (WMHs) and gait may assist in understanding the central control of gait and determining treatment modalities. These relationships are yet to be realized in older people with dementia. OBJECTIVE: To examine the association between WMH volume and gait under single-task and dual task (DT) conditions in people with dementia. METHODS: Twenty-eight community-dwelling older people with dementia (median age=83 years; [IQR=77-86]; 36% female) had timed gait speed assessed at usual pace. Gait (speed, stride length, cadence) was assessed using the GAITRite® mat under three conditions (n = 18/28): a) single-task, b) functional DT: carrying a glass of water and c) cognitive DT: counting backwards from 30. WMH volumes were quantified using a fully automated segmentation toolbox. RESULTS: Total, temporal and parietal WMH volumes were negatively correlated with timed and functional DT gait speed, and with stride length under single-task, functional DT and cognitive DT conditions. Frontal WMH volumes were negatively correlated with timed gait speed and stride length under single-task and functional DT conditions. Participants with higher total WMH burden had significantly slower timed and functional DT gait speed and reduced stride length under single-task, functional DT and cognitive DT conditions compared to participants with lower WMH burden. CONCLUSIONS: WMH volume was associated with slower gait speed and reduced stride length, but not cadence, under single-task and DT conditions in people with dementia. Further research is needed to confirm these findings and determine whether vascular risk management can improve gait in older people with dementia.

Cognitive Domain Associations with Balance Performance in Community-Dwelling Older People with Cognitive Impairment.

BACKGROUND: In older people with cognitive impairment (CI), executive function (EF) has been associated with motor performance including balance and gait. The literature examining and supporting a relationship between balance performance and other cognitive domains is limited. OBJECTIVE: To investigate the relationship between global cognition and cognitive domain function and balance performance in older people with CI. METHODS: The iFOCIS randomized controlled trial recruited 309 community-dwelling older people with CI. Baseline assessments completed before randomization were used for analyses including the Addenbrooke's Cognitive Examination-III (ACE-III; global cognition) and its individual cognitive domains (attention; memory; verbal fluency; language; visuospatial ability) and the Frontal Assessment Battery (FAB), a measure of EF. A composite balance score was derived from postural sway and leaning balance tests. RESULTS: In linear regression analyses adjusted for covariates, global cognition and each cognitive domain were significantly associated with balance performance. EF (verbal fluency; ß= -0.254, p < 0.001, adjusted R2 = 0.387) and visuospatial ability (ß= -0.258, p < 0.001, adjusted R2 = 0.391) had the strongest associations with balance performance. In a comprehensively adjusted multivariable model including all of the ACE-III cognitive domains, visuospatial ability and EF (verbal fluency) were independently and significantly associated with balance performance. CONCLUSION: Poorer global cognition and cognitive domain function were associated with poorer balance performance in this sample of people with CI. Visuospatial ability and EF were independently associated with balance, highlighting potential shared neural networks and the role higher-level cognitive processes and spatial perception/processing play in postural control.

Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy - a case report.

BACKGROUND: We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX. CASE PRESENTATION: A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. In addition, the ABCA4 variant was not identified in the sister originally diagnosed with Stargardt disease. Next generation sequencing identified a heterozygous c.121C > T, p.R41W missense mutation in CRX in all 3 affected members. CONCLUSIONS: We describe a common phenotype, but with variable age at onset, with autosomal dominant inheritance and reduced penetrance in a family found to have a pathogenic sequence variant in CRX. This illustrates the importance of panel based molecular genetic testing accompanied by family studies to establish a definitive diagnosis.

"Genetic and clinical findings in an ethnically diverse retinitis pigmentosa cohort associated with pathogenic variants in EYS".

BACKGROUND AND OBJECTIVES: The EYS gene is an important cause of autosomal recessive retinitis pigmentosa (arRP). The objective of this study is to report on novel pathogenic variants in EYS and the range of associated phenotypes. SUBJECTS AND METHODS: This retrospective case series at a tertiary referral centre for inherited retinal diseases describes patients with an IRD and at least two variants in the EYS gene. Phenotyping included multimodal retinal imaging; genotyping molecular genetic analysis using targeted next generation sequencing. Sanger sequencing verification and analysis of novel variants using in silico approaches to determine their predicted pathogenicity. RESULTS: Eight male and four female patients were included. Age at onset ranged from 11 to 62 years with variable symptom presentation; ten patients showed classical features of retinitis pigmentosa, albeit with great variation in disease severity and extent. Two patients had atypical phenotypes: one with localised inferior sector pigmentation and a mild RP phenotype with changes predominantly at the posterior pole. Eighteen variants in EYS were identified, located across the gene: six were novel. Eight variants were missense, two altered splicing, one was a whole exon duplication and the remainder were predicted to result in premature truncation of the protein. CONCLUSION: The marked variability in severity and age of onset in most patients in this ethnically diverse cohort adds to growing evidence that that mild phenotypes are associated with EYS variants. Similarly, the two atypical cases add to the growing diversity of EYS disease as do the six novel pathogenic variants described.