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.

Rehabilitation after surgery for hip fracture - the impact of prompt, frequent and mobilisation-focused physiotherapy on discharge outcomes: an observational cohort study.

PURPOSE: To determine the relationship between three postoperative physiotherapy activities (time to first postoperative walk, activity on the day after surgery, and physiotherapy frequency), and the outcomes of hospital length of stay (LOS) and discharge destination after hip fracture. METHODS: A cohort study was conducted on 437 hip fracture surgery patients aged ≥ 50 years across 36 participating hospitals from the Australian and New Zealand Hip Fracture Registry Acute Rehabilitation Sprint Audit during June 2022. Study outcomes included hospital LOS and discharge destination. Generalised linear and logistic regressions were used respectively, adjusted for potential confounders. RESULTS: Of 437 patients, 62% were female, 56% were aged ≥ 85 years, 23% were previously living in a residential aged care facility, 48% usually walked with a gait aid, and 38% were cognitively impaired prior to their injury. The median acute and total LOS were 8 (IQR 5-13) and 20 (IQR 8-38) days. Approximately 71% (n = 179/251) of patients originally living in private residence returned home and 29% (n = 72/251) were discharged to a residential aged care facility. Previously mobile patients had a higher total LOS if they walked day 2-3 (10.3 days; 95% CI 3.2, 17.4) or transferred with a mechanical lifter or did not get out of bed day 1 (7.6 days; 95% CI 0.6, 14.6) compared to those who walked day 1 postoperatively. Previously mobile patients from private residence had a reduced odds of return to private residence if they walked day 2-3 (OR 0.38; 95% CI 0.17, 0.87), day 4 + (OR 0.38; 95% CI 0.15, 0.96), or if they only sat, stood or stepped on the spot day 1 (OR 0.29; 95% CI 0.13, 0.62) when compared to those who walked day 1 postoperatively. Among patients from private residence, each additional physiotherapy session per day was associated with a -2.2 (95% CI -3.3, -1.0) day shorter acute LOS, and an increased log odds of return to private residence (OR 1.76; 95% CI 1.02, 3.02). CONCLUSION: Hip fracture patients who walked earlier, were more active day 1 postoperatively, and/or received a higher number of physiotherapy sessions were more likely to return home after a shorter LOS.

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.

Sensorimotor, Cognitive, and Affective Functions Contribute to the Prediction of Falls in Old Age and Neurologic Disorders: An Observational Study.

OBJECTIVE: To determine whether impairments across cognitive and affective domains provide additional information to sensorimotor deficits for fall prediction among various populations. DESIGN: We pooled data from 5 studies for this observational analysis of prospective falls. SETTING: Community or low-level care facility. PARTICIPANTS: Older people (N=1090; 74.0±9.4y; 579 female); 500 neurologically intact (NI) older people and 3 groups with neurologic disorders (cognitive impairment, n=174; multiple sclerosis (MS), n=111; Parkinson disease, n=305). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sensorimotor function was assessed with the Physiological Profile Assessment, cognitive function with tests of executive function, affect with questionnaires of depression, and concern about falling with falls efficacy questionnaires. These variables were associated with fall incidence rates, obtained prospectively over 6-12 months. RESULTS: Poorer sensorimotor function was associated with falls (incidence rate ratio [95% CI], 1.46 [1.28-1.66]). Impaired executive function was the strongest predictor of falls overall (2.91 [2.27-3.73]), followed by depressive symptoms (2.07 [1.56-2.75]) and concern about falling (2.02 [1.61-2.55]). Associations were similar among groups, except for a weaker relationship with executive impairment in NI persons and a stronger relationship with concern about falling in persons with MS. Multivariable analyses showed that executive impairment, poorer sensorimotor performance, depressive symptoms, and concern about falling were independently associated with falls. CONCLUSIONS: Deficits in cognition (executive function) and affect (depressive symptoms) and concern about falling are as important as sensorimotor function for fall prediction. These domains should be included in fall risk assessments for older people and clinical groups.

The role of cognitive function and physical activity in physical decline in older adults across the cognitive spectrum.

OBJECTIVES: The aim of this study was to investigate physical decline over 1-year in a cohort of older people across the cognitive spectrum. METHODS: Physical function was assessed using the Physiological Profile Assessment (PPA) in 593 participants (cognitively normal [CN]: n = 342, mild cognitive impairment [MCI]: n = 77, dementia: n = 174) at baseline and in 490 participants available for reassessment 1-year later. Neuropsychological performance and physical activity (PA) were assessed at baseline. RESULTS: Median baseline PPA scores for CN, MCI and dementia groups were 0.41 (IQR = -0.09-1.02), 0.66 (IQR = -0.06-1.15) and 2.37 (IQR = 0.93-3.78) respectively. All baseline neuropsychological domains and PA were significantly associated with baseline PPA. There were significant interaction terms (Time × Cognitive Group, Global Cognition, Processing Speed, Executive Function and PA) in the models investigating PPA decline. In multivariate analysis the Time × Executive Function and PA interaction terms were significant, indicating that participants with poorer baseline executive function and reduced PA demonstrated greater physical decline when compared to individuals with better executive function and PA respectively. DISCUSSION: Having MCI or dementia is associated with greater physical decline compared to CN older people. Physical inactivity and executive dysfunction were associated with physical decline in this sample, which included participants with MCI and dementia. Both factors influencing physical decline are potentially amenable to interventions e.g. exercise.

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota.

OBJECTIVE: Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). DESIGN: A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. RESULTS: Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or ß diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. CONCLUSION: Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. TRIAL REGISTRATION NUMBER: ISRCTN18662143.

Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations.

BACKGROUND: The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. METHODS: In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen. RESULTS: Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73-88%) (four patients with clinical complete response declined surgery). Twenty-four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05-1.03, P=0.055). CONCLUSIONS: This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss.

Reaction Time and Postural Sway Modify the Effect of Executive Function on Risk of Falls in Older People with Mild to Moderate Cognitive Impairment.

OBJECTIVES: To explore the relationship between cognitive performance and falls in older people with mild to moderate cognitive impairment (CI) by investigating the mediational effects of medical, medication, neuropsychological, and physiological factors. DESIGN: Secondary analysis, prospective cohort study. SETTING: Community and low-level care. PARTICIPANTS: 177 older people (aged 82 ± 7 years) with mild to moderate CI (MMSE 11-23; ACE-R < 83). MEASUREMENTS: Global cognition and six neuropsychological domains (memory, language, visuospatial, processing speed, executive function [EF], and affect) were assessed. Participants also underwent sensorimotor and balance assessments. Falls were recorded prospectively for 12 months. RESULTS: The EF domain was most strongly associated with multiple falls (relative risk [RR]: 1.50, 95% CI: 1.18-1.91). Global cognition was not associated with falls (RR: 1.09, 95% CI: 0.92-1.30). Additional analyses showed that participants with poorer EF (median cutpoint) were more likely to be taking centrally acting medications and were less physically active. They also had significantly worse vision, reaction time, knee extension strength, balance (postural sway, controlled leaning balance), and higher physiological fall risk scores. Participants with poorer EF were 1.5 times (RR: 1.50, 95% CI: 1.03-2.18) more likely to have multiple falls. Mediational analyses demonstrated that reaction time and postural sway reduced the relative risk of EF on multiple falls by 31% (RR: 1.19, 95% CI: 0.81-1.74). CONCLUSIONS: Within this sample of older people with mild to moderate CI, poorer EF increased the risk of multiple falls. This relationship was mediated by reaction time and postural sway,suggesting cognitively impaired older people with poorer EF may benefit from fall prevention programs targeting these mediating factors.

HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials.

HER2 overexpression/amplification is linked to trastuzumab response in breast/gastric cancers. One suggested anti-EGFR resistance mechanism in colorectal cancer (CRC) is aberrant MEK-AKT pathway activation through HER2 up-regulation. We assessed HER2-amplification/overexpression in stage II-III and IV CRC patients, assessing relationships to KRAS/BRAF and outcome. Pathological material was obtained from 1914 patients in the QUASAR stage II-III trial and 1342 patients in stage IV trials (FOCUS and PICCOLO). Tissue microarrays were created for HER2 immunohistochemistry. HER2-amplification was assessed using FISH and copy number variation. KRAS/BRAF mutation status was assessed by pyrosequencing. Progression-free survival (PFS) and overall survival (OS) data were obtained for FOCUS/PICCOLO and recurrence and mortality for QUASAR; 29/1342 (2.2%) stage IV and 25/1914 (1.3%) stage II-III tumours showed HER2 protein overexpression. Of the HER2-overexpressing cases, 27/28 (96.4%) stage IV tumours and 20/24 (83.3%) stage II-III tumours demonstrated HER2 amplification by FISH; 41/47 (87.2%) also showed copy number gains. HER2-overexpression was associated with KRAS/BRAF wild-type (WT) status at all stages: in 5.2% WT versus 1.0% mutated tumours (p < 0.0001) in stage IV and 2.1% versus 0.2% in stage II-III tumours (p = 0.01), respectively. HER2 was not associated with OS or PFS. At stage II-III, there was no significant correlation between HER2 overexpression and 5FU/FA response. A higher proportion of HER2-overexpressing cases experienced recurrence, but the difference was not significant. HER2-amplification/overexpression is identifiable by immunohistochemistry, occurring infrequently in stage II-III CRC, rising in stage IV and further in KRAS/BRAF WT tumours. The value of HER2-targeted therapy in patients with HER2-amplified CRC must be tested in a clinical trial. © 2015 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

A home-based, carer-enhanced exercise program improves balance and falls efficacy in community-dwelling older people with dementia.

BACKGROUND: Older people with dementia are at increased risk of physical decline and falls. Balance and mood are significant predictors of falls in this population. The aim of this study was to determine the effect of a tailored home-based exercise program in community-dwelling older people with dementia. METHODS: Forty-two participants with mild to moderate dementia were recruited from routine health services. All participants were offered a six-month home-based, carer-enhanced, progressive, and individually tailored exercise program. Physical activity, quality of life, physical, and psychological assessments were administered at the beginning and end of the trial. RESULTS: Of 33 participants (78.6%) who completed the six-month reassessment ten (30%) reported falls and six (18%) multiple falls during the follow-up period. At reassessment, participants had better balance (sway on floor and foam), reduced concern about falls, increased planned physical activity, but worse knee extension strength and no change in depression scores. The average adherence to the prescribed exercise sessions was 45% and 22 participants (52%) were still exercising at trial completion. Those who adhered to ≥70% of prescribed sessions had significantly better balance at reassessment compared with those who adhered to <70% of sessions. CONCLUSIONS: This trial of a tailored home-based exercise intervention presents preliminary evidence that this intervention can improve balance, concern about falls, and planned physical activity in community-dwelling older people with dementia. Future research should determine whether exercise interventions are effective in reducing falls and elucidate strategies for enhancing uptake and adherence in this population.

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.

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.

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.

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.

Single-cell nanobiopsy enables multigenerational longitudinal transcriptomics of cancer cells.

Single-cell RNA sequencing has revolutionized our understanding of cellular heterogeneity, but routine methods require cell lysis and fail to probe the dynamic trajectories responsible for cellular state transitions, which can only be inferred. Here, we present a nanobiopsy platform that enables the injection of exogenous molecules and multigenerational longitudinal cytoplasmic sampling from a single cell and its progeny. The technique is based on scanning ion conductance microscopy (SICM) and, as a proof of concept, was applied to longitudinally profile the transcriptome of single glioblastoma (GBM) brain tumor cells in vitro over 72 hours. The GBM cells were biopsied before and after exposure to chemotherapy and radiotherapy, and our results suggest that treatment either induces or selects for more transcriptionally stable cells. We envision the nanobiopsy will contribute to transforming standard single-cell transcriptomics from a static analysis into a dynamic assay.

Physical impairments in cognitively impaired older people: implications for risk of falls.

BACKGROUND: Cognitively impaired older people fall twice as often as their cognitively intact counterparts. There is, however, limited information on factors that increase the risk of falls in this population. This study aimed to determine whether a group of cognitively impaired older people (CIG) perform worse than a matched group of cognitively intact older people (NCIG) on a profile of physical performance and mobility tests. METHODS: One hundred and thirty-eight cognitively impaired and 276 age and gender matched cognitively intact community-dwelling older adults (>60 years) took part in the study. Participants completed a detailed physical performance battery from which composite fall risk scores were derived. Falls were measured prospectively for 12 months with monthly falls diaries, telephone calls, and by regularly contacting participants' "person responsible." RESULTS: The CIG performed worse than the NCIG in tests of reaction time, muscle strength (grip and quadriceps), balance (sway on floor, sway on foam, controlled leaning balance and near tandem standing ability), and mobility (sit to stand, timed up and go (TUG) and steps required to turn 180 degrees). The CIG had significantly higher composite fall risk scores than the NCIG and fell significantly more during follow-up (Multiple falls (2+): CIG 43%; NCIG 21%). CONCLUSIONS: Fall risk in the CIG was significantly increased due to multiple physical impairments. Physical profiles provide a means of quantifying the extent of impairment in older people with cognitive impairment and potential direction for targeting interventions for reducing fall risk.

A feasibility study and pilot randomised trial of a tailored prevention program to reduce falls in older people with mild dementia.

BACKGROUND: People with dementia have a disproportionately high rate of falls and fractures and poorer outcomes, yet there is currently no evidence to guide falls prevention in this population. METHODS: A randomised trial design was used to test feasibility of study components and acceptability of a home hazard reduction and balance and strength exercise fall prevention program. The program was tailored to participant's individual cognitive levels and implemented as a carer-supported intervention. Feasibility of recruitment, retention and implementation of intervention were recorded through observation and documented in field notes. Adherence, carer burden and use of task simplification strategies were also monitored. Outcome measures, collected at 12 weeks included physiological, fear of falling, cognitive and functional measures. RESULTS: Recruitment was achievable but may be more challenging in a multisite trial. Twenty two dyads of persons with mild dementia and their carers were randomised to intervention or usual care control group. Of 38 dyads referred to the study, there was a high rate of willingness to participate, with 6 (16%) declining and 10 (26%) not meeting inclusion criteria. The intervention was well received by participants and carers and adherence to both program components was very good. All participants implemented some home safety recommendations (range 19-80%) with half implementing 50% or more. At the end of 12 weeks, 72% of the intervention group were exercising. Both the rate of falling and the risk of a fall were lower in the intervention group but these findings were not significant (RR= 0.50 (95% CI 0.11-2.19). There were no differences in physiological outcome measures between the control and intervention groups. However results were influenced by the small study size and incomplete data primarily in the intervention group at follow up. CONCLUSIONS: The pilot study was feasible and acceptable to people with mild dementia and their carers. The lessons learnt included: recruitment for a larger trial will require multiple approaches; home safety recommendations should provide a greater emphasis on environmental use compared with behavioural change; strategies to ensure an adequate dosage of exercise should be further explored. We recommend that intervention delivery incorporate an integrated occupational therapy and physiotherapy approach and that carers be provided with an individualised session to enhance dementia-specific skills in management and communication. A refined intervention should be tested in a randomised trial with an adequately powered sample size. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry 126100001049066.

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.