Recent Submissions

  • A systematic review of the cost-effectiveness of community and population interventions to reduce the modifiable risk factors for dementia

    Brain, Jacob; Stephan, Blossom C. M. (2022)
    Population-based health and lifestyle interventions, which change societal conditions such that everyone across a given community is more likely to live more healthily, have been under-researched within the context of dementia prevention and risk reduction. This systematic review finds such interventions highly cost-effective, and often also cost-saving, in both high- as well as low- and middle-income settings. The strongest evidence base was for interventions that changed the physical environment to decrease physical inactivity or obesity, financial interventions that improved access to or resources for education, and mass media programmes that changed the social environment around smoking.
  • Practitioners’ views on enabling people with dementia to remain in their homes during and after crisis

    Coleston-Shields, Donna M.; Stanyon, Miriam R.; Yates, Jennifer A.; Streater, Amy; Orrell, Martin (2022)
    One way of supporting people living with dementia is assisting them to live in their homes (as opposed to being admitted to hospital or other facility) and providing them with a specialist service that responds to crises. This makes it important to understand how best to organize such crisis response services. This study examines practitioners’ actions to reduce inpatient admissions among this population. Through interviews with healthcare practitioners, we find that practitioners negotiate a complex intersection between (1) what constitutes a crisis in relation to the patient and/or the carer, (2) the demands of building a working relationship with both the patient and their family carers, and (3) ensuring effective communications with social services responsible for long-term community support. Findings suggest that policies aimed at reducing admissions should be based on a model of care that more closely maps practitioners’ relational and bio-medical work in these services.
  • Dietary nitrate and brain health. Too much ado about nothing or a solution for dementia prevention?

    Stephan, Blossom C. M. (2022)
    Dementia is a significant public health priority with approximately 55 million cases worldwide, and this number is predicted to quadruple by 2050. Adherence to a healthy diet and achieving optimal nutritional status are vital strategies to improve brain health. The importance of this area of research has been consolidated into the new term ‘nutritional psychiatry’. Dietary nitrate, closely associated with the intake of fruits and vegetables, is a compound that is increased in dietary patterns such as the Mediterranean and MIND diets and has protective effects on cognition and brain health. Nitrate is characterised by a complex metabolism and is the precursor of the nitrate–nitrite–nitric oxide (NO) pathway contributing to systemic NO generation. A higher intake of dietary nitrate has been linked to protective effects on vascular outcomes including blood pressure and endothelial function. However, the current evidence supporting the protective effects of dietary nitrate on brain health is less convincing. This article aims to provide a critical appraisal of the current evidence for dietary nitrate supplementation for improving brain health and provide suggestions for future research.
  • Dementia Early-Stage Cognitive Aids New Trial (DESCANT) of memory aids and guidance for people with dementia: randomised controlled trial

    Orrell, Martin; Challis, David; Chester, Helen; Hughes, Jane (2022)
    Background Common memory aids for people with dementia at home are recommended. However, rigorous evaluation is lacking, particularly what guidance or support is valued.Objective To investigate effects of memory aids and guidance by dementia support practitioners (DSPs) for people in early-stage dementia through a pragmatic, randomised controlled trial.Methods Of 469 people with mild-to-moderate dementia and their informal carers, 468 were randomised to a DSP with memory aids or to usual care plus existing dementia guide. Allocation was stratified by Trust/Health Board; time since first attendance at memory service; gender; age; and living with primary carer or not. Primary outcome was Bristol Activities of Daily Living Scale (BADLS) Score at 3 and 6 months (primary end-point). Secondary outcomes for people with dementia: quality of life (CASP-19; DEMQOL); cognition and functioning (Clinical Dementia Rating Scale; S-MMSE); capability (ICECAP-O); social networks (LSNS-R); and instrumental daily living activities (R-IDDD). Secondary outcomes for carers: psychological health (GHQ-12); sense of competence (SSCQ).Results DSPs were successfully trained, compliance was good and welcomed by participants. Mean 6 months BADLS Score increased to 14.6 (SD: 10.4) in intervention and 12.6 (SD: 8.1) in comparator, indicative of greater dependence in the activities of daily living. Adjusted between-group difference was 0.38 (95% CI: −0.89 to 1.65, p=0.56). Though this suggests greater dependency in the intervention group the difference was not significant. No differences were found in secondary outcomes.Conclusions This intervention did not maintain independence in the activities of daily living with no improvement in other outcomes for people with dementia or carers.Trial registration number Current Controlled Trials ISRCTN12591717.Data are available upon reasonable request. Data are available on reasonable request from the corresponding author
  • Analysing the use of music to facilitate social interaction in care home residents with dementia: Narrative synthesis systematic review

    Waters, Bryony; Orrell, Martin; McDermott, Orii (2022)
    IntroductionIndividuals with dementia residing in care homes can rely heavily on care staff to access activities and meaningful interactions. Previous research suggests that care home interactions can be short, fragmented and task-orientated due to staff workload and residents? language impairments. However, music has the potential to be an alternative communication form that remains intact in the later stages of dementia. This systematic review aims to explore how care home music interventions can facilitate social interactions.MethodsA narrative synthesis was conducted to explore the mechanisms behind how and why care home music intervention facilitate social interactions. The four-element framework guided analysis; (1) Developing a theory, (2) Developing a preliminary synthesis, (3) Exploring relationships, (4) Assessing robustness.FindingsThe final synthesis included 23 articles. The studies consisted of music therapy sessions, personalised music listening, structured music singing or instrument playing sessions and music therapeutic care. Despite the difference in music interventions, most studies reported an increase in residents? sociable verbal and non-verbal communication and a decrease in unsociable communication. Music interventions allowed residents to reminisce, express themselves, focus and connect with others.DiscussionThe studies highlighted music interventions are accessible to all residents with dementia despite their impairments. The adaptability allows individuals to continue to connect and express themselves even when language deteriorates. More research is needed into the enablers and barriers to implementing interventions into practice, as this systematic review has highlighted that some form of music intervention for all residents can be highly beneficial. Care homes use of music could increase social interactions and meaningful activities.
  • Risk factors for dementia in the context of cardiovascular disease: A protocol of an overview of reviews

    Brain, Jacob; Siervo, Mario; Stephan, Blossom C. M. (2022)
    BACKGROUND: Dementia is a major public health priority. Although there is abundant evidence of an association between dementia and poor cardiovascular health, findings have been inconsistent and uncertain in identifying which factors increase dementia risk in those with cardiovascular disease. Indeed, multiple variables including sociodemographic, economic, health, lifestyle and education may indicate who is at higher vs. lower dementia risk and could be used in prediction modelling. Therefore, the aim of this review is to synthesise evidence on the key risk factors for dementia in those with a history of cardiovascular disease. METHODS: This is an overview of reviews protocol, registered on PROSPERO (CRD42021265363). Four electronic databases including MEDLINE, EMBASE, PsycINFO, and the Cochrane Database of Systematic Reviews will be searched. Studies will be included if they are systematic reviews and/or meta-analyses that have investigated the risk of incident dementia (all-cause and subtypes including Alzheimer's disease and vascular dementia) in people with a history of coronary heart disease, heart failure, atrial fibrillation, hypertension, hyperlipidaemia, and vascular stiffness. Study selection will be completed by two independent researchers according to the eligibility criteria, and conflicts resolved by a third reviewer. References will be exported into Covidence for title and abstract sifting, full-text review, and data extraction. Methodological quality will be assessed using the AMSTAR-2 criteria and confidence of evidence will be assessed using the GRADE classification. This overview of reviews will follow PRISMA guidelines. If there is sufficient homogeneity in the data, the results will be pooled, and a meta-analysis conducted to determine the strength of association between each risk factor and incident all-cause dementia and its subtypes for each cardiovascular diagnoses separately. DISCUSSION: We will create a comprehensive summary of the key risk factors linking cardiovascular diseases to risk of incident dementia. This knowledge is essential for informing risk predictive model development as well as the development of risk reduction and prevention strategies.
  • Secular trends in dementia free cognitive function in older adults: A systematic review

    Stephan, Blossom C. M. (2022)
    BACKGROUNDAlthough numerous studies have reported a decrease in dementia risk in the last two decades, it is unclear whether dementia-free cognitive function is also changing across generations.OBJECTIVEThe objective was to systematically evaluate the published data on generational differences in cognitive function in the older population.METHODSSearches were performed on PubMed, Embase, and PsychInfo for articles published in English before 20 June 2021. Included studies were from population-based samples that reported generational differences in cognition in individuals without dementia, aged ≥60 years.RESULTS28,101 studies were identified and 15 selected covering the period from 1971 to 2015: including studies from China, Europe, and the USA. The results show generally consistent findings of improvements or stability in dementia free cognitive function in later versus earlier born generations, but not for all cognitive domains. Prevalence of mild cognitive impairment and cognitive impairment no dementia has remained stable in the USA, UK, and China over the last two decades.RESULTSPrevalence of vascular related mild cognitive impairment has increased in China. Improvements in cognition may only partially be explained by increased educational attainment across generations.CONCLUSIONThis review provides evidence for generational effects in dementia-free cognitive function, predominately stability or improvements in performance, in later compared to earlier born individuals across different world regions. There is an urgent need to determine the factors driving such changes and whether they are being experienced in all world regions, particularly low- and middle-income countries where the burden of cognitive impairment is greatest and rising.
  • A self-management app for people living with mild dementia (PRIDE): Protocol for a pre-post feasibility study

    Lee, Abigail R.; McDermott, Orii; Guo, Boliang; Roe, James; Orrell, Martin (2022)
    BACKGROUND: With the rapid increase in the prevalence of dementia in the United Kingdom and beyond, the emotional, social, and economic burden on individuals, families, and health care services continues to rise. Currently, interventions that enable people living with dementia to better manage their condition and achieve a good quality of life are needed. OBJECTIVE: This study aimed to explore how the Promoting Independence in Dementia (PRIDE) app can promote and support the self-management of people living with mild dementia. METHODS: Feasibility of a pre-post study design incorporating the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework will be studied. We will use up to 6 National Health Service Trusts as research sites and the Join Dementia Research website and accept self-referrals to recruit 60 to 90 people living with mild dementia. Participants will complete the PRIDE app intervention over 8 weeks with support from a dementia adviser facilitator. Measures exploring mood, physical well-being, and quality of life will be collected at baseline and at follow-ups at 3 and 6 months. Facilitators and National Health Service staff will be invited to complete interviews shortly after the intervention phase. RESULTS: Data collection began in June 2021 and is predicted to cease by the end of August 2022. Analysis of the quantitative measures will explore the impact of the PRIDE app on participants' independence, mood, and quality of life. Interview data will discuss participant experiences, how the use of the app affected them, and if it has the potential to be successfully implemented and maintained in dementia services. CONCLUSIONS: This study will show the potential reach, effectiveness, and adoption of the PRIDE app intervention in the lives of people with mild dementia. The findings from this study will inform future research on the PRIDE app and any further developments to improve its effectiveness. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33881.
  • Perceptions of cognitive training games and assessment technologies for dementia: Acceptability study with patient and public involvement workshops

    Harrington, Kyle; Craven, Michael P. (2022)
    BACKGROUNDCognitive training and assessment technologies offer the promise of dementia risk reduction and a more timely diagnosis of dementia, respectively. Cognitive training games may help reduce the lifetime risk of dementia by helping to build cognitive reserve, whereas cognitive assessment technologies offer the opportunity for a more convenient approach to early detection or screening.OBJECTIVEThis study aims to elicit perspectives of potential end users on factors related to the acceptability of cognitive training games and assessment technologies, including their opinions on the meaningfulness of measurement of cognition, barriers to and facilitators of adoption, motivations to use games, and interrelationships with existing health care infrastructure.METHODSFour linked workshops were conducted with the same group, each focusing on a specific topic: meaningful improvement, learning and motivation, trust in digital diagnosis, and barriers to technology adoption. Participants in the workshops included local involvement team members acting as facilitators and those recruited via Join Dementia Research through a purposive selection and volunteer sampling method. Group activities were recorded, and transcripts were analyzed using thematic analysis with a combination of a priori and data-driven themes. Using a mixed methods approach, we investigated the relationships between the categories of the Capability, Opportunity, and Motivation-Behavior change model along with data-driven themes by measuring the φ coefficient between coded excerpts and ensuring the reliability of our coding scheme by using independent reviewers and assessing interrater reliability. Finally, we explored these themes and their relationships to address our research objectives.RESULTSIn addition to discussions around the capability, motivation, and opportunity categories, several important themes emerged during the workshops: family and friends, cognition and mood, work and hobbies, and technology. Group participants mentioned the importance of functional and objective measures of cognitive change, the social aspect of activities as a motivating factor, and the opportunities and potential shortcomings of digital health care provision. Our quantitative results indicated at least moderate agreement on all but one of the coding schemes and good independence of our coding categories. Positive and statistically significant φ coefficients were observed between several coding themes between categories, including a relatively strong positive φ coefficient between capability and cognition (0.468; P<.001).CONCLUSIONSThe implications for researchers and technology developers include assessing how cognitive training and screening pathways would integrate into existing health care systems; however, further work needs to be undertaken to address barriers to adoption and the potential real-world impact of cognitive training and screening technologies.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)RR2-10.1007/978-3-030-49065-2_4.
  • Development of best practice guidance on online peer support for people with young onset dementia: Protocol for a mixed methods study

    Gerritzen, Esther V. (2022)
    BACKGROUND: Many people with young onset dementia (YOD) may feel isolated. Peer support has the potential to improve social health, but the inconsistent availability of age-appropriate, in-person (peer) support services for people with YOD suggests that many people with YOD miss out on the potential benefits. Online peer support could be useful, as it overcomes geographical barriers, offers a variety of options, and adjusts to various needs and preferences. OBJECTIVE: Our study aims to develop evidence-based best practice guidance on online peer support for people with YOD and group facilitators to improve online peer support for people with YOD. METHODS: Our mixed methods study consists of 4 phases and follows the guidelines of the Medical Research Council on complex interventions. Each phase consists of multiple substudies. The study focuses on the development stage of the Medical Research Council framework and additionally develops a plan for the feasibility/piloting, evaluation, and implementation stages. The participants are people living with YOD and peer support facilitators. The qualitative research methods include interviews, focus groups, and open questions in a web-based survey. The quantitative methods include a web-based survey consisting of existing outcome measures. RESULTS: The study is funded by the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions - Innovative Training Networks (H2020-MSCA-ITN-2018; grant agreement number: 813196), and it received ethical approval from the London Bromley Research Ethics Committee (reference number: 21/LO/0248) in April 2021. Recruitment started in May 2021. Data collection and analysis are expected to be finished by September 2022. CONCLUSIONS: The best practice guidance can provide people with YOD with tailored and evidence-based information about online peer support, and it will be disseminated locally (in the United Kingdom) and internationally through dementia organizations, research networks, and academic institutions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38379.
  • Online peer support for people with parkinson disease: Narrative synthesis systematic review

    Gerritzen, Esther V.; Lee, Abigail R.; McDermott, Orii; Orrell, Martin (2022)
    Background: Parkinson disease (PD) significantly impacts the lives of people with the diagnosis and their families. In addition to the physical symptoms, living with PD also has an emotional impact. This can result in withdrawal from social roles, increasing the risk for social isolation and loneliness. Peer support is a way to stay socially connected, share experiences, and learn new coping skills. Peer support can be provided both in person and on the internet. Some of the advantages of online peer support are that it overcomes geographical barriers and provides a form of anonymity; moreover, support can be readily available when needed. However, the psychosocial impact of PD is still underresearched, and there is no systematic synthesis of online peer support for people with PD. Objective: This review aims to explore the benefits and challenges of online peer support and identify successful elements of online peer support for people with PD. Methods: The method selected for this systematic review is narrative synthesis. A total of 6 databases were systematically searched in April 2020 for articles published between 1989 and 2020. The quality of the included studies was assessed using the Critical Appraisal Skills Programme qualitative research checklist and the Downs and Black quality checklist. Results: A total of 10,987 unique articles were identified through a systematic database search. Of these 10,987 articles, 8 (0.07%) were included in this review. Of the 8 studies, 5 (63%) were of good or high quality, 2 (25%) were of medium or fair quality, and 1 (13%) study was of poor quality. Web-based platforms included discussion forums, a web-based virtual world, and Facebook groups. Most papers reported on text-based communication. The included studies reported on sharing social support and personal experiences. Successful elements included increasing similarity between members and offering the opportunity to directly ask questions to a physician. Challenges included members leaving without a warning and PD symptoms hindering the use of technology. Conclusions: Peer support can improve social support and help people with PD in living meaningful and satisfying lives. Peer support is unique and cannot be replaced by family members, friends, or health care professionals. Online peer support can be a solution for those who do not have access to an in-person support group or whose PD symptoms restrict them from travelling. However, research on the personal experiences of those who engage in online peer support and potential barriers in accessing it remains limited. Future research could use qualitative methods to explore these fields further.
  • A systematic literature review and meta-analysis on digital health interventions for people living with dementia and Mild Cognitive Impairment

    Di Lorito, Claudio; Craven, Michael P. (2022)
    Abstract Objectives Digital health interventions enable services to support people living with dementia and Mild Cognitive Impairment (MCI) remotely. This literature review gathers evidence on the effectiveness of digital health interventions on physical, cognitive, behavioural and psychological outcomes, and Activities of Daily Living in people living with dementia and MCI. Methods/Design Searches, using nine databases, were run in November 2021. Two authors carried out study selection/appraisal using the Critical Appraisal Skills Programme checklist. Study characteristics were extracted through the Cochrane handbook for systematic reviews of interventions data extraction form. Data on digital health interventions were extracted through the template for intervention description and replication (TIDieR) checklist and guide. Intervention effectiveness was determined through effect sizes. Meta-analyses were performed to pool data on intervention effectiveness. Results Twenty studies were included in the review, with a diverse range of interventions, modes of delivery, activities, duration, length, frequency, and intensity. Compared to controls, the interventions produced a moderate effect on cognitive abilities (SMD = 0.36; 95% CI = ?0.03 to 0.76; I2 = 61%), and a negative moderate effect on basic ADLs (SMD = ?0.40; 95% CI = ?0.86 to 0.05; I2 = 69%). Stepping exergames generated the largest effect sizes on physical and cognitive abilities. Supervised training produced larger effect sizes than unsupervised interventions. Conclusion Supervised intervention delivery is linked to greatest benefits. A mix of remote and face-to-face delivery could maximise benefits and optimise costs. Accessibility, acceptability and sustainability of digital interventions for end-users must be pre-requisites for the development of future successful services.
  • Exploratory pilot study on resource allocation along the dementia continuum under constrained and unconstrained budget scenarios

    Challis, David (2022)
    People with dementia and their carers have a wide range of health and social care needs which vary along the dementia continuum. The government response to events and transitions at various stages of the continuum can have a substantial impact on the lived experience of dementia and to resource allocation decision-making. Hearing what practitioners have to say about need at various points of transition along the dementia continuum is very important, especially for the resource allocation process.
  • Psychological treatments for depression and anxiety in dementia and mild cognitive impairment

    Orrell, Martin (2022)
    BACKGROUNDExperiencing anxiety and depression is very common in people living with dementia and mild cognitive impairment (MCI). There is uncertainty about the best treatment approach. Drug treatments may be ineffective and associated with adverse effects. Guidelines recommend psychological treatments. In this updated systematic review, we investigated the effectiveness of different psychological treatment approaches.OBJECTIVESPrimary objective To assess the clinical effectiveness of psychological interventions in reducing depression and anxiety in people with dementia or MCI. Secondary objectives To determine whether psychological interventions improve individuals' quality of life, cognition, activities of daily living (ADL), and reduce behavioural and psychological symptoms of dementia, and whether they improve caregiver quality of life or reduce caregiver burden.SEARCH METHODSWe searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases, and three trials registers on 18 February 2021.SELECTION CRITERIAWe included randomised controlled trials (RCTs) that compared a psychological intervention for depression or anxiety with treatment as usual (TAU) or another control intervention in people with dementia or MCI.DATA COLLECTION AND ANALYSISA minimum of two authors worked independently to select trials, extract data, and assess studies for risk of bias. We classified the included psychological interventions as cognitive behavioural therapies (cognitive behavioural therapy (CBT), behavioural activation (BA), problem-solving therapy (PST)); 'third-wave' therapies (such as mindfulness-based cognitive therapy (MBCT)); supportive and counselling therapies; and interpersonal therapies. We compared each class of intervention with control. We expressed treatment effects as standardised mean differences or risk ratios. Where possible, we pooled data using a fixed-effects model. We used GRADE methods to assess the certainty of the evidence behind each result.MAIN RESULTSWe included 29 studies with 2599 participants. They were all published between 1997 and 2020. There were 15 trials of cognitive behavioural therapies (4 CBT, 8 BA, 3 PST), 11 trials of supportive and counselling therapies, three trials of MBCT, and one of interpersonal therapy. The comparison groups received either usual care, attention-control education, or enhanced usual care incorporating an active control condition that was not a specific psychological treatment. There were 24 trials of people with a diagnosis of dementia, and five trials of people with MCI. Most studies were conducted in community settings. We considered none of the studies to be at low risk of bias in all domains.  Cognitive behavioural therapies (CBT, BA, PST) Cognitive behavioural therapies are probably slightly better than treatment as usual or active control conditions for reducing depressive symptoms (standardised mean difference (SMD) -0.23, 95% CI -0.37 to -0.10; 13 trials, 893 participants; moderate-certainty evidence). They may also increase rates of depression remission at the end of treatment (risk ratio (RR) 1.84, 95% CI 1.18 to 2.88; 2 studies, with one study contributing 2 independent comparisons, 146 participants; low-certainty evidence). We were very uncertain about the effect of cognitive behavioural therapies on anxiety at the end of treatment (SMD -0.03, 95% CI -0.36 to 0.30; 3 trials, 143 participants; very low-certainty evidence). Cognitive behavioural therapies probably improve patient quality of life (SMD 0.31, 95% CI 0.13 to 0.50; 7 trials, 459 participants; moderate-certainty evidence) and activities of daily living at end of treatment compared to treatment as usual or active control (SMD -0.25, 95% CI -0.40 to -0.09; 7 trials, 680 participants; moderate-certainty evidence). Supportive and counselling interventions Meta-analysis showed that supportive and counselling interventions may have little or no effect on depressive symptoms in people with dementia compared to usual care at end of treatment (SMD - .05, 95% CI -0.18 to 0.07; 9 trials, 994 participants; low-certainty evidence). We were very uncertain about the effects of these treatments on anxiety, which was assessed only in one small pilot study. Other interventions There were very few data and very low-certainty evidence on MBCT and interpersonal therapy, so we were unable to draw any conclusions about the effectiveness of these interventions.AUTHORS' CONCLUSIONSCBT-based treatments added to usual care probably slightly reduce symptoms of depression for people with dementia and MCI and may increase rates of remission of depression. There may be important effect modifiers (degree of baseline depression, cognitive diagnosis, or content of the intervention). CBT-based treatments probably also have a small positive effect on quality of life and activities of daily living. Supportive and counselling interventions may not improve symptoms of depression in people with dementia. Effects of both types of treatment on anxiety symptoms are very uncertain. We are also uncertain about the effects of other types of psychological treatments, and about persistence of effects over time. To inform clinical guidelines, future studies should assess detailed components of these interventions and their implementation in different patient populations and in different settings.
  • The economic burden of dementia in low- and middle-income countries (LMICs): a systematic review

    Stephan, Blossom C. M. (2022)
    INTRODUCTIONMore than two-thirds of people with dementia live in low- and middle-income countries (LMICs), resulting in a significant economic burden in these settings. In this systematic review, we consolidate the existing evidence on the cost of dementia in LMICs.METHODSSix databases were searched for original research reporting on the costs associated with all-cause dementia or its subtypes in LMICs. The national-level dementia costs inflated to 2019 were expressed as percentages of each country's gross domestic product (GDP) and summarised as the total mean percentage of GDP. The risk of bias of studies was assessed using the Larg and Moss method.RESULTSWe identified 14 095 articles, of which 24 studies met the eligibility criteria. Most studies had a low risk of bias. Of the 138 LMICs, data were available from 122 countries. The total annual absolute per capita cost ranged from US$590.78 for mild dementia to US$25 510.66 for severe dementia. Costs increased with the severity of dementia and the number of comorbidities. The estimated annual total national costs of dementia ranged from US$1.04 million in Vanuatu to US$195 billion in China. The average total national expenditure on dementia estimated as a proportion of GDP in LMICs was 0.45%. Indirect costs, on average, accounted for 58% of the total cost of dementia, while direct costs contributed 42%. Lack of nationally representative samples, variation in cost components, and quantification of indirect cost were the major methodological challenges identified in the existing studies.CONCLUSIONThe estimated costs of dementia in LMICs are lower than in high-income countries. Indirect costs contribute the most to the LMIC cost. Early detection of dementia and management of comorbidities is essential for reducing costs. The current costs are likely to be an underestimation due to limited dementia costing studies conducted in LMICs, especially in countries defined as low- income.PROSPERO REGISTRATION NUMBERThe protocol was registered in the International Prospective Register of Systematic Reviews database with registration number CRD42020191321.
  • Progressing towards blood based diagnostic RNA biomarkers for dementia with lewy bodies

    Rajkumar, Anto P. (2022)
    Prevalence of Dementia with Lewy bodies (DLB) is second only to Alzheimer's disease (AD) among people with neurodegenerative dementia. Accurate distinction between these two most common subtypes of dementia is essential because they differ in their prognosis, neuropsychiatric symptoms, pharmacological management, 1 and sensitivity to medication adverse effects. Misdiagnosing DLB as AD, and prescribing an antipsychotic medication for treating persistent visual hallucinations and associated challenging behaviours may lead to life-threatening adverse events. Moreover, DLB leads to earlier institutionalisation and mortality, more severe neuropsychiatric symptoms, higher costs and more carers’ burden than AD. Currently, there are only three indicative biomarkers helping to diagnose DLB, 1) reduced dopamine transporter uptake in basal ganglia, visualised by Single-Photon Emission Computed Tomography or Positron Emission Tomography, 2) low uptake 123iodine-Meta-iodobenzylguanidine myocardial scintigraphy, and 3) polysomnography confirming rapid eye movement sleep without atonia. 2 These indicative biomarkers are not routinely used in most clinical settings because of costs, equipment availability or concerns over feasibility. There is an urgent clinical need for discovering reliable blood-based biomarkers that can aid differentiating DLB from AD. Such blood-based diagnostic biomarkers hold promise for rapid clinical adoption and for facilitating early diagnosis and accurate subtyping of dementia.
  • Clinical utility of cerebrospinal fluid Aβ42 and tau measures in diagnosing mild cognitive impairment in early onset dementia

    Junaid, Kehinde (2022)
    BACKGROUNDThe differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with early onset Alzheimer's or related dementias (EOARD). We report our experience on diagnostic lumbar puncture to diagnose EOARD at a tertiary neurocognitive referral center in Nottingham, England from March 2018 to October 2020.OBJECTIVETo assess amyloid-β42 (Aβ42), total tau, and Thr181-phosphorylated tau (p-tau) measurements in the cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and in relation to their follow-up cognitive performance.METHODSThirty participants aged 32-68 years old (mean 59 years; 57% female) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, neuroradiological features (MRI, FDG-PET CT) and CSF Aβ42, total tau, and p-tau measurements.RESULTSPatients with MCI who progressed to AD (prodromal AD) had significantly higher CSF total (797.63 pg/ml) and p-tau (82.31 pg/ml), and lower Aβ42 levels (398.94 pg/ml) in comparison to their counterparts with stable MCI (total tau 303.67 pg/ml, p-tau 43.56 pg/ml, Aβ42 873.44 pg/ml) (p <  0.01 for CSF total and p-tau measures and p <  0.0001 for CSF Aβ42 measures). None of the CSF biomarkers correlated with any of the cognitive performance measures. Principal component analysis confirmed that the clinical diagnosis of MCI secondary to AD, namely prodromal AD (as per NIA-AA criteria) in younger adults, was associated with decreased CSF Aβ42.CONCLUSIONIn early onset AD, low levels of CSF Aβ42 appear to be more sensitive than total and p-tau measures in differentiating AD MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness of making an earlier diagnosis.
  • Olfactory stimulation for people with dementia: A rapid review

    Dening, Tom (2022)
    There is a growing interest in using olfactory (smell) stimulation in dementia care. This study aims to extend current knowledge by synthesising the evidence on the efficacy of interventions using olfactory stimulation for people with dementia and to assess the effects of different types of odours and administration methods using a mixed methods approach. The rapid review was conducted based on searches in six electronic databases. A narrative approach was applied to assess 20 studies included in the review. Fourteen studies used a quasi-experimental design, five studies used an experimental design and one was a case study. High heterogeneity was found on odours and methods of application used, with the majority of studies administering lavender oil using a diffuser. Mixed results were reported on the benefits of olfactory stimulation on responsive behaviours and cognitive function. Although the evidence available is limited, encouraging results were found regarding olfactory stimulation and increased sleep duration, food intake and improved balance. It was not possible to draw any overall conclusion in relation to the effect of olfactory stimulation. However, this review shows promising results that support further investigation of olfactory stimulation as a nonpharmacological intervention for people with dementia. The review is limited due to the low to moderate quality of studies included. Furthermore, the broad range of approaches was employed, and comparison between the studies was difficult. Further high-quality mixed method studies using robust and detailed protocols are needed to clarify the effects of olfactory stimuli and any other factors that may influence the responses of people with dementia.
  • Risk of conversion from mild cognitive impairment to dementia in low- and middle-income countries: A systematic review and meta-analysis

    Yates, Jennifer A.; Stephan, Blossom C. M. (2022)
    IntroductionWith no treatment for dementia, there is a need to identify high risk cases to focus preventive strategies, particularly in low- and middle-income countries (LMICs) where the burden of dementia is greatest. We evaluated the risk of conversion from mild cognitive ompairment (MCI) to dementia in LMICs.MethodsMedline, Embase, PsycINFO, and Scopus were searched from inception until June 30, 2020. The search was restricted to observational studies, conducted in population-based samples, with at least 1 year follow-up. There was no restriction on the definition of MCI used as long as it was clearly defined. PROSPERO registration: CRD42019130958.ResultsTen thousand six hundred forty-seven articles were screened; n = 11 retained. Of the 11 studies, most were conducted in China (n = 7 studies), with only two studies from countries classified as low income. A qualitative analysis of n = 11 studies showed that similar to high-income countries the conversion rate to dementia from MCI was variable (range 6 . 0%-44 . 8%; average follow-up 3 . 7 years [standard deviation = 1 . 2]). A meta-analysis of studies using Petersen criteria (n = 6 studies), found a pooled conversion rate to Alzheimer's disease (AD) of 23 . 8% (95% confidence interval = 15 . 4%-33.4%); approximately one in four people with MCI were at risk of AD in LMICs (over 3 . 0-5 . 8 years follow-up). Risk factors for conversion from MCI to dementia included demographic (e.g., age) and health (e.g., cardio-metabolic disease) variables.ConclusionsMCI is associated with high, but variable, conversion to dementia in LMICs and may be influenced by demographic and health factors. There is a notable absence of data from low-income settings and countries outside of China. This highlights the urgent need for research investment into aging and dementia in LMIC settings. Being able to identify those individuals with cognitive impairment who are at highest risk of dementia in LMICs is necessary for the development of risk reduction strategies that are contextualized to these unique settings.
  • Systematic review of pharmacological interventions for people with Lewy body dementia

    Watts, Katrina E.; Storr, Nicholas J.; Barr, Phoebe G.; Rajkumar, Anto P. (2022)
    OBJECTIVELewy body dementia (LBD) is the second most common neurodegenerative dementia, and it causes earlier mortality and more morbidity than Alzheimer's disease. Reviewing current evidence on its pharmacological management is essential for developing evidence-based clinical guidelines, and for improving the quality of its clinical care. Hence, we systematically reviewed all studies that investigated the efficacy of any medication for managing various symptoms of LBD.METHODWe identified eligible studies by searching 15 databases comprehensively. We completed quality assessment, extracted relevant data, and performed GRADE assessment of available evidence. We conducted meta-analyses when appropriate (PROSPERO:CRD42020182166).RESULTSWe screened 18,884 papers and included 135 studies. Our meta-analyses confirmed level-1 evidence for Donepezil's efficacy of managing cognitive symptoms of dementia with Lewy bodies (DLB) (SMD = 0.63; p < 0.001) and Parkinson's Disease Dementia (PDD) (SMD = 0.43; p < 0.01), and managing hallucinations in DLB (SMD=-0.52; p = 0.02). Rivastigmine and Memantine have level-2 evidence for managing cognitive and neuropsychiatric symptoms of DLB. Olanzapine and Yokukansan have similar evidence for managing DLB neuropsychiatric symptoms. Level-2 evidence support the efficacy of Rivastigmine and Galantamine for managing cognitive and neuropsychiatric symptoms of PDD.CONCLUSIONWe list evidence-based recommendations for the pharmacological management of DLB and PDD, and propose specific clinical guidelines for improving their clinical management.Supplemental data for this article can be accessed online at https://doi.org/10.1080/13607863.2022.2032601 .

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