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1.
BMC Neurol ; 24(1): 127, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627686

ABSTRACT

BACKGROUND: Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer's disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10-20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia. METHODS: Aim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50-92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30-40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50-100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis. DISCUSSION: This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Female , Aged , Middle Aged , Aged, 80 and over , Male , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/psychology , Smartphone , Prospective Studies , Cross-Sectional Studies , Reproducibility of Results , Cognitive Dysfunction/diagnosis , Biomarkers , Amyloid beta-Peptides
2.
Disabil Rehabil ; : 1-8, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38655713

ABSTRACT

PURPOSE: People with dementia often experience poor outcomes in hospital and prolonged lengths of stay. They are sometimes labelled as having "poor rehabilitation potential". This study aimed to understand the inpatient rehabilitation experiences of people with dementia or cognitive impairment, and their support people, to inform future work to improve rehabilitation access and outcomes. MATERIALS AND METHODS: An exploratory qualitative study from an interpretivist perspective. Participants were inpatients of a geriatric rehabilitation unit in Australia, and their chosen support people. Semi-structured interviews were audio-recorded and transcribed. An analytical framework was developed and indexed to the dataset, followed by charting and thematic analysis. RESULTS: Ten people with dementia or cognitive impairment and nine support people participated (n = 19). Four themes were identified representing an interpretation of the analysis intended to inform clinical practice: Support patients to engage in the rehabilitation process; create a hospitable environment; recognise and work with care partners; and ensure staff have adequate dementia knowledge. CONCLUSIONS: Practical, emotional, process-related, and dementia-specific factors may influence the experiences of people living with dementia or cognitive impairment when participating in inpatient rehabilitation. Future research could investigate whether improvements focused on these factors might enhance quality of care for people with dementia.


People living with dementia may require tailored support to engage in the rehabilitation process effectively.Safe, kind, and comfortable environments provide a strong foundation for good rehabilitation care for people with dementia or cognitive impairment.Involving family as care partners may be essential for some people living with dementia.Dementia knowledge for the geriatric rehabilitation workforce may improve clinical outcomes.

3.
Nat Genet ; 56(4): 579-584, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38575728

ABSTRACT

Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN protein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSN PTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity.


Subject(s)
Diabetes Mellitus, Type 2 , Induced Pluripotent Stem Cells , Liver Diseases , Nerve Tissue Proteins , Adult , Humans , Adaptor Proteins, Signal Transducing/genetics , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Nerve Tissue Proteins/genetics , Obesity/complications , Obesity/genetics , Proteomics
4.
Physiotherapy ; 123: 47-55, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38271742

ABSTRACT

OBJECTIVES: To 1) explore physiotherapy students' experience in caring for people with dementia; 2) develop a rich understanding of their perceived preparedness to work with people with dementia upon graduation; and 3) identify opportunities to improve dementia education from the perspectives of students. DESIGN: A qualitative study comprised of semi-structured interviews via web conferencing software. Thematic analysis was undertaken, with themes/subthemes derived and a qualitative framework generated. SETTING: Three Victorian Universities in Australia. PARTICIPANTS: Physiotherapy students of entry-to-professional practice education programs (n = 17; mean age 23.7 years, 65% female), having completed at least 15 weeks of clinical placements. RESULTS: The overarching theme was that students' experience of providing care for people with dementia was variable. The three sub-themes were: 1) students experience significant challenges when working with people with dementia, 2) students experience a range of emotions when working with people with dementia, and 3) the quality of dementia learning experiences during entry-to-professional practice training is mostly inadequate. Students described the importance of the supervisor during clinical placements, and suggested incorporating 'real-life' scenario training in the classroom to assist them learn to manage the challenging symptoms of dementia. CONCLUSION: Physiotherapy students believe that entry-to-practice dementia education is insufficient. These findings have important implications for the future planning and delivery of physiotherapy dementia education. CONTRIBUTION OF THE PAPER.


Subject(s)
Dementia , Qualitative Research , Humans , Dementia/rehabilitation , Female , Male , Young Adult , Students, Health Occupations/psychology , Attitude of Health Personnel , Adult , Physical Therapy Specialty/education , Clinical Competence , Interviews as Topic
5.
Alzheimers Dement (Amst) ; 16(1): e12520, 2024.
Article in English | MEDLINE | ID: mdl-38274411

ABSTRACT

INTRODUCTION: Low-cost simple tests for preclinical Alzheimer's disease are a research priority. We evaluated whether remote unsupervised webcam recordings of finger-tapping were associated with cognitive performance in older adults. METHODS: A total of 404 cognitively-asymptomatic participants (64.6 [6.77] years; 70.8% female) completed 10-second finger-tapping tests (Tasmanian [TAS] Test) and cognitive tests (Cambridge Neuropsychological Test Automated Battery [CANTAB]) online at home. Regression models including hand movement features were compared with null models (comprising age, sex, and education level); change in Akaike Information Criterion greater than 2 (ΔAIC > 2) denoted statistical difference. RESULTS: Hand movement features improved prediction of episodic memory, executive function, and working memory scores (ΔAIC > 2). Dominant hand features outperformed nondominant hand features for episodic memory (ΔAIC = 2.5), executive function (ΔAIC = 4.8), and working memory (ΔAIC = 2.2). DISCUSSION: This brief webcam test improved prediction of cognitive performance compared to age, sex, and education. Finger-tapping holds potential as a remote language-agnostic screening tool to stratify community cohorts at risk for cognitive decline.

6.
Aust Health Rev ; 48(1): 66-81, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38245911

ABSTRACT

Objective My Therapy is an allied health guided, co-designed rehabilitation self-management program for residents of aged care facilities. This study aimed to determine the feasibility of implementing My Therapy in a residential aged care setting. Methods This observational study was conducted on a 30-bed wing, within a 90-bed metropolitan residential aged care facility, attached to a public health service, in Victoria, Australia. Staff and resident data were collected prospectively over 6 weeks (staff focus groups, patient surveys, and audits) to evaluate the feasibility domains of acceptability , reach and demand , practicality , integration , limited efficacy testing and adaptations . Results Twenty-six residents and five allied health staff (physiotherapy and occupational therapy) participated. My Therapy was acceptable to residents (survey) and staff (focus groups). Via initial My Therapy discussions between the resident and the therapists, to determine goals and resident preferences, My Therapy reached 26 residents (n = 26/26, 100% program reach ), with 15 residents subsequently receiving a rehabilitation program (n = 15/26, 58% program demand ). The remaining 11 residents did not participate due to resident preference or safety issues (n = 11/26, 42%). Collecting physical function outcome measures for limited efficacy testing was practical , and the cost of My Therapy was AUD$6 per resident per day, suggesting financial integration may be possible. Several adaptations were required, due to limited allied health staff, complex resident goal setting and program co-design. Conclusion My Therapy has the potential to improve the rehabilitation reach of allied health services in residential aged care. While introducing this low-cost intervention is feasible, adaptations were required for successful implementation.


Subject(s)
Homes for the Aged , Occupational Therapy , Aged , Humans , Feasibility Studies , Health Services , Victoria
7.
Alzheimers Dement ; 20(1): 173-182, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37519032

ABSTRACT

INTRODUCTION: Finding low-cost methods to detect early-stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home-based Tasmanian (TAS) Test keyboard tapping tests predict episodic memory performance. METHODS: 1169 community participants (65.8 ± 7.4 years old; 73% female) without cognitive symptoms completed online single-key and alternate-key tapping tests and episodic memory, working memory, and executive function cognitive tests. RESULTS: All single-key (R2 adj  = 8.8%, ΔAIC = 5.2) and alternate-key (R2 adj  = 9.1%, ΔAIC = 8.8) motor features predicted episodic memory performance relative to demographic and mood confounders only (R2 adj  = 8.1%). No tapping features improved estimation of working memory. DISCUSSION: Brief self-administered online hand movement tests predict asymptomatic episodic memory impairment. This provides a potential low-cost home-based method for stratification of enriched cohorts. HIGHLIGHTS: We devised two brief online keyboard tapping tests to assess hand motor function. 1169 cognitively asymptomatic adults completed motor- and cognitive tests online. Impaired hand motor function predicted reduced episodic memory performance. This brief self-administered test may aid stratification of community cohorts.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Memory, Episodic , Humans , Female , Aged , Middle Aged , Male , Cross-Sectional Studies , Cognitive Dysfunction/psychology , Memory Disorders/diagnosis , Alzheimer Disease/complications , Neuropsychological Tests
8.
BMJ Open ; 13(10): e076005, 2023 10 28.
Article in English | MEDLINE | ID: mdl-37898485

ABSTRACT

INTRODUCTION: Evidence suggests that the pathology underlying cognitive decline leading to dementia begins 15-20 years before cognitive symptoms emerge. Thus, identifying biomarkers in this preclinical phase is critically important. Age-related decrease in muscle mass and strength, a known risk factor for sarcopenia, frailty and cognitive decline, also affects the tongue. This paper describes an a priori protocol by a multidisciplinary team to address the following questions relating to adults ≥50 years of age: (1) What is the current evidence on the association of tongue strength with cognitive decline? (2) How does tongue strength associate with frailty and sarcopenia? (3) What is the association of tongue strength with nutritional health? METHODS AND ANALYSIS: Search terms will be identified then multiple electronic databases (PubMed, PsycINFO (Ovid), Scopus, Embase (Ovid), CINAHL and Web of Science) searched systematically for peer-reviewed articles published in English that address the following inclusion criteria: (1) human studies, (2) participants ≥50 years of age and (3) studies with tongue pressure values measured in relation to at least one of the following: frailty, sarcopenia, nutritional health, cognitive function and dementia (Alzheimer's, vascular, frontotemporal and Lewy body). Grey literature also will be searched to identify additional studies, clinical trials and policy papers appropriate for inclusion. The search will be from database inception. After removing duplicates, two research team members will independently screen abstracts and identify articles for full-text review. The team will use a data charting tool for data extraction. Data will be analysed quantitatively and qualitatively. ETHICS AND DISSEMINATION: The scoping review does not require ethics approval as data will be from publicly available sources. Results will be disseminated in workshops and conferences and a peer-reviewed journal paper.


Subject(s)
Cognitive Dysfunction , Dementia , Frailty , Sarcopenia , Humans , Aged , Sarcopenia/complications , Frailty/complications , Pressure , Tongue , Cognitive Dysfunction/complications , Risk Factors , Research Design , Dementia/diagnosis , Review Literature as Topic
9.
Int J Geriatr Psychiatry ; 38(8): e5988, 2023 08.
Article in English | MEDLINE | ID: mdl-37592719

ABSTRACT

OBJECTIVES: Unequal access to cognitive assessments is a major barrier to timely diagnosis, especially for those living in rural or remote areas. 'One-stop' cognitive clinic models are a proposed solution, but few such clinics exist. We evaluate the implementation of a new one-stop State-wide clinic model in Tasmania, Australia, where 27% of people live in rural/remote areas. METHODS: A novel single-visit protocol has been developed, comprising interdisciplinary medical and cognitive assessments, research participation, consensus diagnosis and management plan. A cross-sectional evaluation was undertaken using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework and results benchmarked against the national Australian Dementia Network Registry. RESULTS: Over the first 52 consecutive weekly clinics: Reach: 130 adults were assessed (mean age [SD] 70.12 years [10.31]; 59.2% female) with 40 (36.8%) from rural/remote areas. EFFECTIVENESS: 98.5% (128/130) received a same-day diagnosis: 30.1% (n = 40) Subjective Cognitive Decline, 35.4% (46) Mild Cognitive Impairment, 33.1% (43) dementia and one case inconclusive. Adoption: 22.9% (156) of General Practitioners referred patients. IMPLEMENTATION: Nearly all 'ideal' diagnostic clinical practices were met and >90% of surveyed patients reported 'good/very good' clinic experience. The wait from referral to diagnosis was 2 months shorter than other national Registry clinics (78 vs. 133 days). CONCLUSIONS: This 'one-stop' model provides an interdisciplinary consensus cognitive diagnosis quickly and is well accepted; this may reduce health inequities especially for people living in rural/remote areas. This cognitive clinic model may be of relevance to other centres worldwide and also provides a rich data source for research studies.


Subject(s)
Dementia , Health Status Disparities , Humans , Female , Aged , Male , Cross-Sectional Studies , Rural Health , Australia , Registries , Health Inequities , Cognition , Dementia/diagnosis
10.
Cell Rep Med ; 4(8): 101155, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37586323

ABSTRACT

New approaches are needed to treat people whose obesity and type 2 diabetes (T2D) are driven by specific mechanisms. We investigate a deletion on chromosome 16p11.2 (breakpoint 2-3 [BP2-3]) encompassing SH2B1, a mediator of leptin and insulin signaling. Phenome-wide association scans in the UK (N = 502,399) and Estonian (N = 208,360) biobanks show that deletion carriers have increased body mass index (BMI; p = 1.3 × 10-10) and increased rates of T2D. Compared with BMI-matched controls, deletion carriers have an earlier onset of T2D, with poorer glycemic control despite higher medication usage. Cystatin C, a biomarker of kidney function, is significantly elevated in deletion carriers, suggesting increased risk of renal impairment. In a Mendelian randomization study, decreased SH2B1 expression increases T2D risk (p = 8.1 × 10-6). We conclude that people with 16p11.2 BP2-3 deletions have early, complex obesity and T2D and may benefit from therapies that enhance leptin and insulin signaling.


Subject(s)
Diabetes Mellitus, Type 2 , Insulins , Metabolic Diseases , Humans , Leptin , Diabetes Mellitus, Type 2/genetics , Obesity/genetics , Adaptor Proteins, Signal Transducing
11.
Geroscience ; 45(6): 3449-3473, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37337026

ABSTRACT

Upper limb motor function is a potential new biomarker of cognitive impairment and may aid discrimination from healthy ageing. However, it remains unclear which assessments to use. This study aimed to explore what methods have been used and to describe associations between upper limb function and cognitive impairment. A scoping review was conducted using PubMed, CINAHL and Web of Science. A systematic search was undertaken, including synonyms for key concepts 'upper limb', 'motor function' and 'cognitive impairment'. Selection criteria included tests of upper limb motor function and impaired cognition in adults. Analysis was by narrative synthesis. Sixty papers published between 1998 and 2022, comprising 41,800 participants, were included. The most common assessment tasks were finger tapping, Purdue Pegboard Test and functional tasks such as writing. Protocols were diverse in terms of equipment used and recording duration. Most participants were recruited from clinical settings. Alzheimer's Disease was the most common cause of cognitive impairment. Results were mixed but, generally, slower speed, more errors, and greater variability in upper limb movement variables was associated with cognitive impairment. This review maps the upper limb motor function assessments used and summarises the available evidence on how these associate with cognitive impairment. It identifies research gaps and may help guide protocols for future research. There is potential for upper limb motor function to be used in assessments of cognitive impairment.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Upper Extremity
12.
Nat Commun ; 14(1): 1450, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36922513

ABSTRACT

Disruption of brain-expressed G protein-coupled receptor-10 (GPR10) causes obesity in animals. Here, we identify multiple rare variants in GPR10 in people with severe obesity and in normal weight controls. These variants impair ligand binding and G protein-dependent signalling in cells. Transgenic mice harbouring a loss of function GPR10 variant found in an individual with obesity, gain excessive weight due to decreased energy expenditure rather than increased food intake. This evidence supports a role for GPR10 in human energy homeostasis. Therapeutic targeting of GPR10 may represent an effective weight-loss strategy.


Subject(s)
Obesity , Receptors, G-Protein-Coupled , Animals , Humans , Mice , Energy Metabolism , Mice, Transgenic , Obesity/genetics , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Signal Transduction , Weight Gain/genetics
13.
Australas J Ageing ; 42(3): 499-507, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36527306

ABSTRACT

OBJECTIVE: To understand the barriers and enablers to participation in family-assisted therapy for older people in Transition Care. METHODS: A qualitative study, underpinned by interpretive description, was conducted at two public health services in Melbourne, Australia. Participants included patients in Transition Care, or their family members, who either participated in or chose not to participate in a family-assisted therapy trial. Semi-structured interviews were conducted, transcribed verbatim and analysed thematically. RESULTS: Forty-four participants were interviewed (17 patients and 27 family members). The unifying theme was to let families decide about participation in family-assisted therapy. The unifying theme was illustrated by three subthemes. The first, what is possible for the family now, described practical considerations including geography, paid and unpaid work structure and commitments and the presence of fit and willing social networks. The second, what is important to the family now, recognised the role of family priorities in deciding. Physical rehabilitation and extra therapy were of high importance to some families. For others, emotional support or searching for a residential aged care bed were more important at the time. Finally, how the family functions described the complexity of relationships and family history that impacted the decision to participate. CONCLUSIONS: The decision to participate in family-assisted therapy is complex and is best made by patients and their families. Clinicians offering family-assisted therapy are encouraged to avoid assuming what will or will not work for families and instead, to let families decide.


Subject(s)
Transitional Care , Humans , Aged , Family/psychology , Australia , Social Networking , Qualitative Research
14.
Physiother Theory Pract ; 39(4): 794-802, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35042447

ABSTRACT

PURPOSE: To explore the experiences of physiotherapy students on working with people with dementia during their clinical placements. METHODS: Qualitative study using a Web-based survey of students in a 2-year entry-level Masters of Physical Therapy (MPT) program. Students were asked to reflect on their experiences during clinical placements within the MPT program. Qualitative content analysis was used to analyze the survey responses. RESULTS: A total of 55 students (93%) completed the survey. Two overarching themes were mastery and inequity. Mastery described dementia care physiotherapy as a complex and potentially rewarding area of practice, requiring education and development throughout the professional continuum from student to expert. Inequity captured the barriers people with dementia experience to receiving excellent physiotherapy care. Six categories supported the themes: 1) physiotherapist characteristics for a successful therapeutic relationship; 2) communication strategies; 3) best practice physiotherapy skills and knowledge; 4) education strategies; 5) desire to work with people living with dementia; and 6) equity. CONCLUSIONS: The study found physiotherapy students' experiences were informed by the preceptors' approach to delivery of care for people living with dementia. The students also articulated areas they wish they had known before placement and provided suggestions for teaching development in this area.


Subject(s)
Clinical Competence , Dementia , Humans , Students , Qualitative Research , Physical Therapy Modalities , Dementia/therapy
15.
Nat Med ; 28(12): 2537-2546, 2022 12.
Article in English | MEDLINE | ID: mdl-36536256

ABSTRACT

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed obesity and reduced social exploratory behavior; female mice heterozygous for the same variant showed similar deficits with reduced severity. Using the 5-HT2CR agonist lorcaserin, we found that depolarization of appetite-suppressing proopiomelanocortin neurons was impaired in knock-in mice. In conclusion, we demonstrate that 5-HT2CR is involved in the regulation of human appetite, weight and behavior. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying HTR2C variants. We suggest that HTR2C should be included in diagnostic gene panels for severe childhood-onset obesity.


Subject(s)
Obesity, Morbid , Receptor, Serotonin, 5-HT2C , Animals , Child , Female , Humans , Male , Mice , HEK293 Cells , Obesity/genetics , Receptor, Serotonin, 5-HT2C/genetics , Serotonin , Serotonin 5-HT2 Receptor Agonists/pharmacology , Adaptation, Psychological
16.
Nat Commun ; 13(1): 5733, 2022 09 29.
Article in English | MEDLINE | ID: mdl-36175420

ABSTRACT

MicroRNAs (miRNAs) modulate physiological responses by repressing the expression of gene networks. We found that global deletion of microRNA-7 (miR-7), the most enriched miRNA in the hypothalamus, causes obesity in mice. Targeted deletion of miR-7 in Single-minded homolog 1 (Sim1) neurons, a critical component of the hypothalamic melanocortin pathway, causes hyperphagia, obesity and increased linear growth, mirroring Sim1 and Melanocortin-4 receptor (MC4R) haplo-insufficiency in mice and humans. We identified Snca (α-Synuclein) and Igsf8 (Immunoglobulin Superfamily Member 8) as miR-7 target genes that act in Sim1 neurons to regulate body weight and endocrine axes. In humans, MIR-7-1 is located in the last intron of HNRNPK, whose promoter drives the expression of both genes. Genetic variants at the HNRNPK locus that reduce its expression are associated with increased height and truncal fat mass. These findings demonstrate that miR-7 suppresses gene networks involved in the hypothalamic melanocortin pathway to regulate mammalian energy homeostasis.


Subject(s)
Melanocortins , MicroRNAs , Animals , Homeostasis/genetics , Humans , Immunoglobulins , Mammals , Melanocortins/genetics , Mice , MicroRNAs/genetics , Obesity/genetics , Receptor, Melanocortin, Type 4/genetics , Transcription Factors , alpha-Synuclein
17.
Comput Biol Med ; 147: 105776, 2022 08.
Article in English | MEDLINE | ID: mdl-35780600

ABSTRACT

BACKGROUND: Telemedicine video consultations are rapidly increasing globally, accelerated by the COVID-19 pandemic. This presents opportunities to use computer vision technologies to augment clinician visual judgement because video cameras are so ubiquitous in personal devices and new techniques, such as DeepLabCut (DLC) can precisely measure human movement from smartphone videos. However, the accuracy of DLC to track human movements in videos obtained from laptop cameras, which have a much lower FPS, has never been investigated; this is a critical gap because patients use laptops for most telemedicine consultations. OBJECTIVES: To determine the validity and reliability of DLC applied to laptop videos to measure finger tapping, a validated test of human movement. METHOD: Sixteen adults completed finger-tapping tests at 0.5 Hz, 1 Hz, 2 Hz, 3 Hz and at maximal speed. Hand movements were recorded simultaneously by a laptop camera at 30 frames per second (FPS) and by Optotrak, a 3D motion analysis system at 250 FPS. Eight DLC neural network architectures (ResNet50, ResNet101, ResNet152, MobileNetV1, MobileNetV2, EfficientNetB0, EfficientNetB3, EfficientNetB6) were applied to the laptop video and extracted movement features were compared to the ground truth Optotrak motion tracking. RESULTS: Over 96% (529/552) of DLC measures were within +/-0.5 Hz of the Optotrak measures. At tapping frequencies >4 Hz, there was progressive decline in accuracy, attributed to motion blur associated with the laptop camera's low FPS. Computer vision methods hold potential for moving us towards intelligent telemedicine by providing human movement analysis during consultations. However, further developments are required to accurately measure the fastest movements.


Subject(s)
COVID-19 , Telemedicine , Adult , Computers , Humans , Movement , Pandemics , Reproducibility of Results
18.
BMC Neurol ; 22(1): 266, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-35850660

ABSTRACT

BACKGROUND: The worldwide prevalence of dementia is rapidly rising. Alzheimer's disease (AD), accounts for 70% of cases and has a 10-20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify individuals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust 'self-testing' data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. METHODS: Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. DISCUSSION: This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen individuals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05194787 , 18 January 2022. Retrospectively registered.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/psychology , Amyloid beta-Peptides , Biomarkers , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Cross-Sectional Studies , Humans , Neuropsychological Tests , Prospective Studies , tau Proteins
19.
Phys Ther ; 102(5)2022 05 05.
Article in English | MEDLINE | ID: mdl-35157773

ABSTRACT

OBJECTIVE: The purpose of this study was to determine physical therapists' and physical therapist students' attitudes and beliefs, knowledge, and confidence in working with people with dementia. METHODS: This was a mixed-methods systematic review. Participants included physical therapists working in any clinical specialty and physical therapist students who had completed at least 1 clinical placement. Eleven databases were searched. The evidence was evaluated using the Joanna Briggs Institute Critical Appraisal Checklists. Data synthesis followed a convergent integrated approach according to Joanna Briggs Institute methodology for mixed-methods systematic reviews. Quantitative data were "qualitized" using thematic analysis and synthesized with qualitative data using thematic synthesis. RESULTS: Fifteen 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 1 theme related to confidence (lack of confidence in working with people with dementia). CONCLUSIONS: Physical therapists and physical therapist students believe that working with people with dementia can be challenging. The low levels of knowledge and confidence in areas important to working with people who have dementia suggest that more education about dementia is needed. IMPACT: This mixed-methods systematic review highlights that physical therapists and physical therapist students believe that working with people who have dementia is complex and challenging. Physical therapists want more training and support in this growing area of practice.


Subject(s)
Dementia , Physical Therapists , Attitude , Humans , Qualitative Research , Students
20.
J Biomed Inform ; 127: 104030, 2022 03.
Article in English | MEDLINE | ID: mdl-35183766

ABSTRACT

BACKGROUND & OBJECTIVE: With populations aging, the number of people with dementia worldwide is expected to triple to 152 million by 2050. Seventy percent of cases are due to Alzheimer's disease (AD) pathology and there is a 10-20 year 'pre-clinical' period before significant cognitive decline occurs. We urgently need, cost effective, objective biomarkers to detect AD, and other dementias, at an early stage. Risk factor modification could prevent 40% of cases and drug trials would have greater chances of success if participants are recruited at an earlier stage. Currently, detection of dementia is largely by pen and paper cognitive tests but these are time consuming and insensitive to the pre-clinical phase. Specialist brain scans and body fluid biomarkers can detect the earliest stages of dementia but are too invasive or expensive for widespread use. With the advancement of technology, Artificial Intelligence (AI) shows promising results in assisting with detection of early-stage dementia. This scoping review aims to summarise the current capabilities of AI-aided digital biomarkers to aid in early detection of dementia, and also discusses potential future research directions. METHODS & MATERIALS: In this scoping review, we used PubMed and IEEE Xplore to identify relevant papers. The resulting records were further filtered to retrieve articles published within five years and written in English. Duplicates were removed, titles and abstracts were screened and full texts were reviewed. RESULTS: After an initial yield of 1,463 records, 1,444 records were screened after removal of duplication. A further 771 records were excluded after screening titles and abstracts, and 496 were excluded after full text review. The final yield was 177 studies. Records were grouped into different artificial intelligence based tests: (a) computerized cognitive tests (b) movement tests (c) speech, conversion, and language tests and (d) computer-assisted interpretation of brain scans. CONCLUSIONS: In general, AI techniques enhance the performance of dementia screening tests because more features can be retrieved from a single test, there are less errors due to subjective judgements and AI shifts the automation of dementia screening to a higher level. Compared with traditional cognitive tests, AI-based computerized cognitive tests improve the discrimination sensitivity by around 4% and specificity by around 3%. In terms of speech, conversation and language tests, combining both acoustic features and linguistic features achieve the best result with accuracy around 94%. Deep learning techniques applied in brain scan analysis achieves around 92% accuracy. Movement tests and setting smart environments to capture daily life behaviours are two potential future directions that may help discriminate dementia from normal aging. AI-based smart environments and multi-modal tests are promising future directions to improve detection of dementia in the earliest stages.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/diagnosis , Artificial Intelligence , Cognitive Dysfunction/diagnosis , Early Diagnosis , Humans , Sensitivity and Specificity
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