Predictors and prognosis of population-based subjective cognitive decline: longitudinal evidence from the Caerphilly Prospective Study (CaPS).

OBJECTIVES: To understand associations between the subjective experience of cognitive decline and objective cognition. This subjective experience is often conceptualised as an early step towards neurodegeneration, but this has not been scrutinised at the population level. An alternative explanation is poor meta-cognition, the extreme of which is seen in functional cognitive disorder (FCD). DESIGN: Prospective cohort (Caerphilly Prospective Study). SETTING: Population-based, South Wales, UK. PARTICIPANTS: This men-only study began in 1979; 1225 men participated at an average age of 73 in 2002-2004, including assessments of simple subjective cognitive decline (sSCD, defined as a subjective report of worsening memory or concentration). Dementia outcomes were followed up to 2012-2014. Data on non-completers was additionally obtained from death certificates and local health records. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was incident dementia over 10 years. Secondary outcome measures included prospective change in objective cognition and cross-sectional cognitive internal inconsistency (the existence of a cognitive ability at some times, and its absence at other times, with no intervening explanatory factors except for focus of attention). RESULTS: sSCD was common (30%) and only weakly associated with prior objective cognitive decline (sensitivity 36% (95% CI 30 to 42) and specificity 72% (95% CI 68 to 75)). Independent predictors of sSCD were older age, poor sleep quality and higher trait anxiety. Those with sSCD did not have excess cognitive internal inconsistency, but results suggested a mild attentional deficit. sSCD did not predict objective cognitive change (linear regression coefficient -0.01 (95% CI -0.13 to 0.15)) nor dementia (odds ratio 1.35 (0.61 to 2.99)) 10 years later. CONCLUSIONS: sSCD is weakly associated with prior objective cognitive decline and does not predict future cognition. Prior sleep difficulties and anxiety were the most robust predictors of sSCD. sSCD in the absence of objective decline appears to be a highly prevalent example of poor meta-cognition (ie, poor self-awareness of cognitive performance), which could be a driver for later FCD.

A Diagnostic Test Accuracy Study Investigating General Practitioner Clinical Impression and Brief Cognitive Assessments for Dementia in Primary Care, Compared to Specialized Assessment.

BACKGROUND: Many health systems are interested in increasing the number of uncomplicated and typical dementia diagnoses that are made in primary care, but the comparative accuracy of tests is unknown. OBJECTIVE: Calculate diagnostic accuracy of brief cognitive tests in primary care. METHODS: We did a diagnostic test accuracy study in general practice, in people over 70 years who had consulted their GP with cognitive symptoms but had no prior diagnosis of dementia. The reference standard was specialist assessment, adjudicated for difficult cases, according to ICD-10. We assessed 16 index tests at a research clinic, and additionally analyzed referring GPs clinical judgement. RESULTS: 240 participants had a median age of 80 years, of whom 126 were men and 132 had dementia. Sensitivity of individual tests at the recommended thresholds ranged from 56% for GP judgement (specificity 89%) to 100% for MoCA (specificity 16%). Specificity of individual tests ranged from 4% for Sniffin' sticks (sensitivity 100%) to 91% for Timed Up and Go (sensitivity 23%). The 95% centile of test duration in people with dementia ranged from 3 minutes for 6CIT and Time and Change, to 16 minutes for MoCA. Combining tests with GP judgement increased test specificity and decreased sensitivity: e.g., MoCA with GP Judgement had specificity 87% and sensitivity 55%. CONCLUSIONS: Using GP judgement to inform selection of tests was an efficient strategy. Using IQCODE in people who GPs judge as having dementia and 6CIT in people who GPs judge as having no dementia, would be a time-efficient and accurate diagnostic assessment.The original protocol for the study is available at https://bmcfampract.biomedcentral.com/articles/10.1186/s12875-016-0475-2.

Decline in Cognition from Mid-Life Improves Specificity of Mini-Mental State Examination: Diagnostic Test Accuracy in Caerphilly Prospective Study (CaPs).

BACKGROUND: The merit of using baseline cognitive assessments in mid-life to help interpret cross-sectional cognitive tests scores in later life is uncertain. OBJECTIVE: Evaluate how accuracy for diagnosing dementia is enhanced by comparing cross-sectional results to a midlife measure. METHODS: Cohort study of 2,512 men with repeated measures of Mini-Mental State Examination (MMSE) over approximately 10 years. Index test MMSE at threshold of 24 indicating normal, as a cross-sectional measure and in combination with decline in MMSE score from mid-life. Reference standard consensus clinical diagnosis of dementia by two clinicians according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). RESULTS: 1,150 men participated at phase 4 of whom 75 had dementia. A cross-sectional MMSE alone produced a sensitivity of 60% (50% to 70%) and specificity 95% (94% to 97%) with a threshold of≥24 points indicating normal. For lower-scoring men in late life, with cross sectional scores of < 22, combining cross-sectional AND a three-point or more decline over time had a sensitivity of 52% (39% to 64%) and specificity 99% (99% to 100%). For higher-scoring men in later life, with cross sectional scores < 26 combining cross-sectional OR decline of at least three points had a sensitivity of 98% (92% to 100%) and specificity 38% (32% to 44%). CONCLUSION: It may be helpful in practice to formally evaluate cognition in mid-life as a baseline to compare with if problems develop in future, as this may enhance diagnostic accuracy and classification of people in later life.

Reaction Time Decomposition as a Tool to Study Subcortical Ischemic Vascular Cognitive Impairment.

BACKGROUND: The study of reaction time (RT) and its intraindividual variability (IIV) in aging, cognitive impairment, and dementia typically fails to investigate the processing stages that contribute to an overall response. Applying "mental chronometry" techniques makes it possible to separately assess the role of processing components during environmental interaction. OBJECTIVE: To determine whether RT and IIV-decomposition techniques can shed light on the nature of underlying deficits in subcortical ischemic vascular cognitive impairment (VCI). Using a novel iPad task, we examined whether VCI deficits occur during both initiation and movement phases of a response, and whether they are equally reflected in both RT and IIV. METHODS: Touch cancellation RT and its IIV were measured in a group of younger adults (n = 22), cognitively healthy older adults (n = 21), and patients with VCI (n = 21) using an iPad task. RESULTS: Whereas cognitively healthy aging affected the speed (RT) of response initiation and movement but not its variability (IIV), VCI resulted in both slowed RT and increased IIV for both response phases. Furthermore, there were group differences with respect to response phase. CONCLUSION: These results indicate that IIV can be more sensitive than absolute RT in separating VCI from normal aging. Furthermore, compared to cognitively healthy aging, VCI was characterized by significant deficits in planning/initiating action as well as performing movements. Such deficits have important implications for real life actions such as driving safety, employment, and falls risk.

Feasibility of remote Memory Clinics using the plan, do, study, act (PDSA) cycle.

INTRODUCTION: A timely diagnosis of dementia is crucial for initiating and maintaining support for people living with dementia. The coronavirus disease (COVID) pandemic temporarily halted Memory Clinics, where this is organised, and rate of dementia diagnosis has fallen. Despite increasing use of alternatives to face-to-face (F2F) consultations in other departments, it is unclear whether this is feasible within the traditional Memory Clinic model. AIMS: The main aim of this service improvement project performed during the pandemic was to explore feasibility of telephone (TC) and videoconference (VC) Memory Clinic consultations. METHODS: Consecutive patients on the Memory Clinic waiting list were telephoned and offered an initial appointment by VC or TC. Data extracted included: age, internet-enabled device ownership, reason for and choice of Memory Clinic assessment. We noted Montreal Cognitive Assessment-Blind (TC) and Addenbrooke's Cognitive Examination-III (VC via Attend Anywhere) scores, and feasibility of consultation. RESULTS: Out of 100 patients, 12 had a home assessment, moved away, been hospitalised, or died. 45, 21 and 6 preferred F2F, VC and TC assessments respectively. 16 were not contactable and offered a F2F appointment. The main reason for preferring F2F was non-ownership, or inability to use an internet-enabled device (80%). VC and TC preference reasons were unwillingness to come to hospital (59%), and convenience (41%). Attendance rate was 100% for VC and TC, but 77% for F2F. Feasibility (successful consultations) was seen in 90% (VC) and 67% (TC) patients. CONCLUSION: For able and willing patients, remote Memory Consultations can be both feasible and beneficial. This has implications for future planning in dementia services.

Inhibitory control deficits in vascular cognitive impairment revealed using the MILO task.

We used the MILO (Multi-Item Localization) task to characterise the performance of a group of older adults diagnosed with mild to moderate vascular cognitive impairment (VCI). The MILO task is designed to explore the temporal context of visual search and in addition to measuring overall completion time, provides a profile of serial reaction time (SRT) patterns across all items in a sequence. Of particular interest here is the Vanish/Remain MILO manipulation that can identify problems with inhibitory control during search. Typically, SRT functions closely overlap, regardless of whether items Vanish or Remain visible when selected, indicating an ability to ignore previously selected targets. Based on the distributed nature of VCI-related pathology and previous visual search studies from our group, we speculated that MILO performance would be compromised in this group of participants when items remained visible after being selected relative to when they vanished. Compared to cognitively healthy, age-matched control participants, the performance of VCI participants was characterised by overall slowing, increased error rates, and crucially, a compromised ability to ignore past locations. As predicted, the Vanish versus Remain SRT functions of VCI participants significantly diverged towards the end of the sequence, which was not the case for control groups. Overall, our findings suggest that the MILO task could be a useful tool for identifying non-age-related changes in behaviour with patient populations, and more generally hints at a possible inhibitory deficit in VCI.

Effect of Probiotic Use on Antibiotic Administration Among Care Home Residents: A Randomized Clinical Trial.

Importance: Probiotics are frequently used by residents in care homes (residential homes or nursing homes that provide residents with 24-hour support for personal care or nursing care), although the evidence on whether probiotics prevent infections and reduce antibiotic use in these settings is limited. Objective: To determine whether a daily oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 compared with placebo reduces antibiotic administration in care home residents. Design, Setting, and Participants: Placebo-controlled randomized clinical trial of 310 care home residents, aged 65 years and older, recruited from 23 care homes in the United Kingdom between December 2016 and May 2018, with last follow-up on October 31, 2018. Interventions: Study participants were randomized to receive a daily capsule containing a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 (total cell count per capsule, 1.3 × 1010 to 1.6 × 1010) (n = 155), or daily matched placebo (n = 155), for up to 1 year. Main Outcomes and Measures: The primary outcome was cumulative antibiotic administration days for all-cause infections measured from randomization for up to 1 year. Results: Among 310 randomized care home residents (mean age, 85.3 years; 66.8% women), 195 (62.9%) remained alive and completed the trial. Participant diary data (daily data including study product use, antibiotic administration, and signs of infection) were available for 98.7% randomized to the probiotic group and 97.4% randomized to placebo. Care home residents randomized to the probiotic group had a mean of 12.9 cumulative systemic antibiotic administration days (95% CI, 0 to 18.05), and residents randomized to placebo had a mean of 12.0 days (95% CI, 0 to 16.95) (absolute difference, 0.9 days [95% CI, -3.25 to 5.05]; adjusted incidence rate ratio, 1.13 [95% CI, 0.79 to 1.63]; P = .50). A total of 120 care home residents experienced 283 adverse events (150 adverse events in the probiotic group and 133 in the placebo group). Hospitalizations accounted for 94 of the events in probiotic group and 78 events in the placebo group, and deaths accounted for 33 of the events in the probiotic group and 32 of the events in the placebo group. Conclusions and Relevance: Among care home residents in the United Kingdom, a daily dose of a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 did not significantly reduce antibiotic administration for all-cause infections. These findings do not support the use of probiotics in this setting. Trial Registration: ISRCTN Identifier:16392920.

Next steps after diagnosing dementia: interventions to help patients and families.

The way that a diagnosis of dementia is delivered to patients, what information is provided and what practical advice and support is arranged has a lasting impact and deserves at least as much attention as the process of assessment and investigation. Individuals and their families require an honest yet sensitive discussion about the nature and cause of their problems, using non-technical language and tailored to their priorities and needs. This should lead on to the provision of good-quality information in an accessible format. Priorities for intervention include medication review, attention to sensory deficits, appropriate pharmacological and nonpharmacological treatment, best use of memory aids and strategies and discussion of driving eligibility, financial entitlement and legal advice. Referral onwards should be made to an appropriate individual or service to provide ongoing emotional and practical support and signposting.

Reaction Time and Visible White Matter Lesions in Subcortical Ischemic Vascular Cognitive Impairment.

Slowed behavioral reaction time is associated with pathological brain changes, including white matter lesions, the common clinical characteristic of subcortical ischemic vascular cognitive impairment (SIVCI). In the present study, reaction time (RT) employing Trails B of the Trail Making Test, with responses capped at 300 s, was investigated in SIVCI (n = 27) compared to cognitively healthy aging (CH) (n = 26). RT was significantly slowed in SIVCI compared to CH (Cohen's d effect size = 1.26). Furthermore, failure to complete Trails B within 300 s was also a characteristic of SIVCI although some ostensibly cognitively healthy older adults also failed to complete within this time limit. Within the SIVCI group, RT did not differ significantly with respect to whether the patients were classified as having moderate/severe or mild, periventricular white matter changes visible on their diagnostic CT/MRI scans. This, together with the high degree of overlap in RT between the two SIVCI subgroups, raises the possibility that using visible ratings scales in isolation may lead to the underestimation of disease level.

Subcortical Ischemic Vascular Cognitive Impairment: Insights from Reaction Time Measures.

In this study, reaction time (RT), intraindividual variability (IIV), and errors, and the effects of practice and processing load upon such function, were compared in patients with subcortical ischemic vascular cognitive impairment (SIVCI) [n = 27] and cognitively healthy older adults (CH) [n = 26]. Compared to CH aging, SIVCI was characterized by a profile of significantly slowed RT, raised IIV, and higher error levels, particularly in the presence of distracting stimuli, indicating that the integrity and/or accessibility of the additional functions required to support high processing load, serial search strategies, are reduced in SIVCI. Furthermore, although practice speeded RT in SIVCI, unlike CH, practice did not lead to an improvement in IIV. This indicates that improvement in RT in SIVCI can in fact mask an abnormally high degree of IIV. Because IIV appears more related to disease, function, and health than RT, its status and potential for change may represent a particularly meaningful, and relevant, disease characteristic of SIVCI. Finally, a high level of within-group variation in the above measures was another characteristic of SIVCI, with such processing heterogeneity in patients with ostensibly the same diagnosis, possibly related to individual variation in pathological load. Detailed measurement of RT, IIV, errors, and practice effects therefore reveal a degree of functional impairment in brain processing not apparent by measuring RT in isolation.

Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer's disease.

We studied resting-state oscillatory connectivity using magnetoencephalography in healthy young humans (N = 183) genotyped for APOE-ɛ4, the greatest genetic risk for Alzheimer's disease (AD). Connectivity across frequencies, but most prevalent in alpha/beta, was increased in APOE-ɛ4 in a set of mostly right-hemisphere connections, including lateral parietal and precuneus regions of the Default Mode Network. Similar regions also demonstrated hyperactivity, but only in gamma (40-160 Hz). In a separate study of AD patients, hypoconnectivity was seen in an extended bilateral network that partially overlapped with the hyperconnected regions seen in young APOE-ɛ4 carriers. Using machine-learning, AD patients could be distinguished from elderly controls with reasonable sensitivity and specificity, while young APOE-e4 carriers could also be distinguished from their controls with above chance performance. These results support theories of initial hyperconnectivity driving eventual profound disconnection in AD and suggest that this is present decades before the onset of AD symptomology.

Goal-oriented cognitive rehabilitation for early-stage Alzheimer's and related dementias: the GREAT RCT.

BACKGROUND: Cognitive rehabilitation (CR) is an individualised, person-centred intervention for people with mild to moderate dementia that addresses the impact of cognitive impairment on everyday functioning. OBJECTIVES: To determine whether or not CR is a clinically effective and cost-effective intervention for people with mild to moderate Alzheimer's disease or vascular or mixed dementia, and their carers. DESIGN: This multicentre randomised controlled trial compared CR with treatment as usual (TAU). Following a baseline assessment and goal-setting to identify areas of everyday functioning that could be improved or better managed, participants were randomised (1 : 1) via secure web access to an independent randomisation centre to receive either TAU or CR and followed up at 3 and 9 months post randomisation. SETTING: Community. PARTICIPANTS: Participants had an International Classification of Diseases, Tenth Edition, diagnosis of Alzheimer's disease or vascular or mixed dementia, had mild to moderate cognitive impairment (Mini Mental State Examination score of ≥ 18 points), were stable on medication if prescribed, and had a family carer who was willing to contribute. The exclusion criteria were people with a history of brain injury or other neurological disorder and an inability to speak English. To achieve adequate power, we needed 350 people to complete the trial, with 175 people in each trial arm. INTERVENTION: Cognitive rehabilitation consisted of 10 therapy sessions over 3 months, followed by four maintenance sessions over 6 months, delivered in participants' homes. The therapists were nine occupational therapists and one nurse. OUTCOME MEASURES: The primary outcome was self-reported goal attainment at 3 months. Goal attainment was also assessed at 9 months. Carers provided independent ratings of goal attainment at both time points. The secondary outcomes were participant quality of life, mood, self-efficacy and cognition, and carer stress, health status and quality of life. The assessments at 3 and 9 months were conducted by researchers who were blind to the participants' group allocation. RESULTS: A total of 475 participants were randomised (CR arm, n = 239; TAU arm, n = 236), 427 participants (90%) completed the trial and 426 participants were analysed (CR arm, n = 208, TAU arm, n = 218). At 3 months, there were statistically significant large positive effects for participant-rated goal attainment [mean change in the CR arm: 2.57; mean change in the TAU arm: 0.86; Cohen'sd = 0.97, 95% confidence interval (CI) 0.75 to 1.19], corroborated by carer ratings (Cohen'sd = 1.11, 95% CI 0.89 to 1.34). These effects were maintained at 9 months for both the participant ratings (Cohen's d = 0.94, 95% CI 0.71 to 1.17) and the carer ratings (Cohen's d = 0.96, 95% CI 0.73 to 1.20). There were no significant differences in the secondary outcomes. In the cost-utility analyses, there was no evidence of cost-effectiveness in terms of gains in the quality-adjusted life-years (QALYs) of the person with dementia (measured using the DEMentia Quality Of Life questionnaire utility score) or the QALYs of the carer (measured using the EuroQol-5 Dimensions, three-level version) from either cost perspective. In the cost-effectiveness analyses, by reference to the primary outcome of participant-rated goal attainment, CR was cost-effective from both the health and social care perspective and the societal perspective at willingness-to-pay values of £2500 and above for improvement in the goal attainment measure. There was no evidence on the cost-effectiveness of the self-efficacy measure (the Generalized Self-Efficacy Scale) from either cost perspective. LIMITATIONS: Possible limitations arose from the non-feasibility of using observational outcome measures, the lack of a general measure of functional ability and the exclusion of people without a carer or with rarer forms of dementia. CONCLUSIONS: Cognitive rehabilitation is clinically effective in enabling people with early-stage dementia to improve their everyday functioning in relation to individual goals targeted in the therapy sessions. FUTURE WORK: Next steps will focus on the implementation of CR into NHS and social care services and on extending the approach to people with rarer forms of dementia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21027481. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 10. See the NIHR Journals Library website for further project information.

BACKGROUND: Cognitive rehabilitation (CR) is a personalised intervention to help people with early-stage dementia to manage everyday activities. This individualised therapy is conducted in people's own homes over several sessions. A therapist works with the person and the carer to identify realistic and relevant goals, plan how to tackle these and support people in achieving them. Previous small studies suggested that CR could be beneficial. METHODS: The Goal-oriented cognitive Rehabilitation in Early-stage Alzheimer's and related dementias: multicentre single-blind randomised controlled Trial (GREAT) was run in eight centres to find out whether or not CR improves everyday functioning. Participants were in the early stages of having Alzheimer's disease, vascular dementia or mixed dementia, with a family carer involved. At the first assessment, participants identified areas in which they would like to see improvements, and set goals. Participants and carers rated how well participants were currently doing in relation to these goals and completed questionnaires, for example about mood and quality of life. Participants were then randomly selected to either receive CR or continue with treatment as usual (TAU). CR consisted of 10 weekly sessions with the therapist over 3 months, followed by four sessions over the next 6 months. Participants were reassessed after 3 and 9 months. RESULTS: We included 475 participants, and 427 participants (90%) completed the trial (209 participants in the CR arm and 218 participants in the TAU arm). After 3 months, the ratings by both participants and carers in the CR group showed that participants were doing significantly better in relation to their goals, and this was maintained 6 months later. Ratings for the TAU-arm participants did not improve significantly. There were no other differences between the groups. There was a strong economic case for CR. CONCLUSIONS: Cognitive rehabilitation is effective in enabling people with early-stage dementia to improve their everyday functioning in relation to individual goals targeted in the therapy sessions. Next steps will focus on the implementation of CR into NHS and social care services.

Individual goal-oriented cognitive rehabilitation to improve everyday functioning for people with early-stage dementia: A multicentre randomised controlled trial (the GREAT trial).

OBJECTIVES: To determine whether individual goal-oriented cognitive rehabilitation (CR) improves everyday functioning for people with mild-to-moderate dementia. DESIGN AND METHODS: Parallel group multicentre single-blind randomised controlled trial (RCT) comparing CR added to usual treatment (CR) with usual treatment alone (TAU) for people with an ICD-10 diagnosis of Alzheimer, vascular or mixed dementia, and mild-to-moderate cognitive impairment (Mini-Mental State Examination [MMSE] score ≥ 18), and with a family member willing to contribute. Participants allocated to CR received 10 weekly sessions over 3 months and four maintenance sessions over 6 months. Participants were followed up 3 and 9 months post randomisation by blinded researchers. The primary outcome was self-reported goal attainment at 3 months. Secondary outcomes at 3 and 9 months included informant-reported goal attainment, quality of life, mood, self-efficacy, and cognition and study partner stress and quality of life. RESULTS: We randomised (1:1) 475 people with dementia; 445 (CR = 281) were included in the intention to treat analysis at 3 months and 426 (CR = 208) at 9 months. At 3 months, there were statistically significant large positive effects for participant-rated goal attainment (d = 0.97; 95% CI, 0.75-1.19), corroborated by informant ratings (d = 1.11; 95% CI, 0.89-1.34). These effects were maintained at 9 months for both participant (d = 0.94; 95% CI, 0.71-1.17) and informant (d = 0.96; 95% CI, 0.73-1.2) ratings. The observed gains related to goals directly targeted in the therapy. There were no significant differences in secondary outcomes. CONCLUSIONS: CR enables people with early-stage dementia to improve their everyday functioning in relation to individual goals targeted in the therapy.

The role of biomarkers and imaging in the clinical diagnosis of dementia.

Recognition of dementia relies on a good clinical history, supported by formal cognitive testing, but identifying the subtype of dementia may be wrong in 20% or more of cases. Accuracy may be improved by use of imaging and cerebrospinal fluid (CSF) biomarkers. Structural neuroimaging is recommended for most patients, not just to identify potentially reversible surgical pathology, but also to detect vascular changes and patterns of cerebral atrophy. Functional imaging can help to confirm neurodegeneration and to distinguish dementia subtypes when structural imaging has been inconclusive. Amyloid-positron emission tomography scans reflect neuritic plaque burden and identify the earliest pathological changes in Alzheimer's disease, but their value outside research settings is still uncertain. A combination of low CSF amyloid ß1-42 and high CSF total-tau or phospho-tau also has high predictive power for AD pathology, but diagnostic usefulness decreases with age because of the increased prevalence of AD-type pathology in non-demented people. The need to use biomarkers more routinely will become necessary as disease-modifying treatments become available and accurate subtype diagnosis will be required at an early (ideally pre-dementia) stage. Clinicians should be considering the resources and expertise that will soon be needed for optimal dementia diagnosis.

Managing diabetes in people with dementia: a realist review.

BACKGROUND: Dementia and diabetes mellitus are common long-term conditions that coexist in a large number of older people. People living with dementia and diabetes may be at increased risk of complications such as hypoglycaemic episodes because they are less able to manage their diabetes. OBJECTIVES: To identify the key features or mechanisms of programmes that aim to improve the management of diabetes in people with dementia and to identify areas needing further research. DESIGN: Realist review, using an iterative, stakeholder-driven, four-stage approach. This involved scoping the literature and conducting stakeholder interviews to develop initial programme theories, systematic searches of the evidence to test and develop the theories, and the validation of programme theories with a purposive sample of stakeholders. PARTICIPANTS: Twenty-six stakeholders (user/patient representatives, dementia care providers, clinicians specialising in dementia or diabetes and researchers) took part in interviews and 24 participated in a consensus conference. DATA SOURCES: The following databases were searched from 1990 to March 2016: MEDLINE (PubMed), Cumulative Index to Nursing and Allied Health Literature, Scopus, The Cochrane Library (including the Cochrane Database of Systematic Reviews), Database of Abstracts of Reviews of Effects, the Health Technology Assessment (HTA) database, NHS Economic Evaluation Database, AgeInfo (Centre for Policy on Ageing - UK), Social Care Online, the National Institute for Health Research (NIHR) portfolio database, NHS Evidence, Google (Google Inc., Mountain View, CA, USA) and Google Scholar (Google Inc., Mountain View, CA, USA). RESULTS: We included 89 papers. Ten papers focused directly on people living with dementia and diabetes, and the rest related to people with dementia or diabetes or other long-term conditions. We identified six context-mechanism-outcome (CMO) configurations that provide an explanatory account of how interventions might work to improve the management of diabetes in people living with dementia. This includes embedding positive attitudes towards people living with dementia, person-centred approaches to care planning, developing skills to provide tailored and flexible care, regular contact, family engagement and usability of assistive devices. A general metamechanism that emerges concerns the synergy between an intervention strategy, the dementia trajectory and social and environmental factors, especially family involvement. A flexible service model for people with dementia and diabetes would enable this synergy in a way that would lead to the improved management of diabetes in people living with dementia. LIMITATIONS: There is little evidence relating to the management of diabetes in people living with dementia, although including a wider literature provided opportunities for transferable learning. The outcomes in our CMOs are largely experiential rather than clinical. This reflects the evidence available. Outcomes such as increased engagement in self-management are potential surrogates for better clinical management of diabetes, but this is not proven. CONCLUSIONS: This review suggests that there is a need to prioritise quality of life, independence and patient and carer priorities over a more biomedical, target-driven approach. Much current research, particularly that specific to people living with dementia and diabetes, identifies deficiencies in, and problems with, current systems. Although we have highlighted the need for personalised care, continuity and family-centred approaches, there is much evidence to suggest that this is not currently happening. Future research on the management of diabetes in older people with complex health needs, including those with dementia, needs to look at how organisational structures and workforce development can be better aligned to the needs of people living with dementia and diabetes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015020625. FUNDING: The NIHR HTA programme.

A comprehensive approach to reablement in dementia.

As society grapples with an aging population and increasing prevalence of disability, "reablement" as a means of maximizing functional ability in older people is emerging as a potential strategy to help promote independence. Reablement offers an approach to mitigate the impact of dementia on function and independence. This article presents a comprehensive reablement approach across seven domains for the person living with mild-to-moderate dementia. Domains include assessment and medical management, cognitive disability, physical function, acute injury or illness, assistive technology, supportive care, and caregiver support. In the absence of a cure or ability to significantly modify the course of the disease, the message for policy makers, practitioners, families, and persons with dementia needs to be "living well with dementia", with a focus on maintaining function for as long as possible, regaining lost function when there is the potential to do so, and adapting to lost function that cannot be regained. Service delivery and care of persons with dementia must be reoriented such that evidence-based reablement approaches are integrated into routine care across all sectors.

Perception and Reality of Cognitive Function: Information Processing Speed, Perceived Memory Function, and Perceived Task Difficulty in Older Adults.

This study examines the relationships between two measures of information processing speed associated with executive function (Trail Making Test and a computer-based visual search test), the perceived difficulty of the tasks, and perceived memory function (measured by the Memory Functioning Questionnaire) in older adults (aged 50+ y) with normal general health, cognition (Montreal Cognitive Assessment score of 26+), and mood. The participants were recruited from the community rather than through clinical services, and none had ever sought or received help from a health professional for a memory complaint or mental health problem. For both the trail making and the visual search tests, mean information processing speed was not correlated significantly with perceived memory function. Some individuals did, however, reveal substantially slower information processing speeds (outliers) that may have clinical significance and indicate those who may benefit most from further assessment and follow up. For the trail making, but not the visual search task, higher levels of subjective memory dysfunction were associated with a greater perception of task difficulty. The relationship between actual information processing speed and perceived task difficulty also varied with respect to the task used. These findings highlight the importance of taking into account the type of task and metacognition factors when examining the integrity of information processing speed in older adults, particularly as this measure is now specifically cited as a key cognitive subdomain within the diagnostic framework for neurocognitive disorders.

What works for whom in the management of diabetes in people living with dementia: a realist review.

BACKGROUND: Dementia and diabetes mellitus are common long-term conditions and co-exist in a large number of older people. People living with dementia (PLWD) may be less able to manage their diabetes, putting them at increased risk of complications such as hypoglycaemia. The aim of this review was to identify key mechanisms within different interventions that are likely to improve diabetes outcomes in PLWD. METHODS: This is a realist review involving scoping of the literature and stakeholder interviews to develop theoretical explanations of how interventions might work, systematic searches of the evidence to test and develop the theories and their validation with a purposive sample of stakeholders. Twenty-six stakeholders - user/patient representatives, dementia care providers, clinicians specialising in diabetes or dementia and researchers - took part in interviews, and 24 participated in a consensus conference. RESULTS: We included 89 papers. Ten focused on PLWD and diabetes, and the remainder related to people with either dementia, diabetes or other long-term conditions. We identified six context-mechanism-outcome configurations which provide an explanatory account of how interventions might work to improve the management of diabetes in PLWD. This includes embedding positive attitudes towards PLWD, person-centred approaches to care planning, developing skills to provide tailored and flexible care, regular contact, family engagement and usability of assistive devices. An overarching contingency emerged concerning the synergy between an intervention strategy, the dementia trajectory and social and environmental factors, especially family involvement. CONCLUSIONS: Evidence highlighted the need for personalised care, continuity and family-centred approaches, although there was limited evidence that this happens routinely. This review suggests there is a need for a flexible service model that prioritises quality of life, independence and patient and carer priorities. Future research on the management of diabetes in older people with complex health needs, including those with dementia, needs to look at how organisational structures and workforce development can be better aligned to their needs. TRIAL REGISTRATION: PROSPERO, CRD42015020625. Registered on 18 May 2015.

Alzheimer's disease disrupts alpha and beta-band resting-state oscillatory network connectivity.

OBJECTIVE: Neuroimaging studies in Alzheimer's disease (AD) yield conflicting results due to selective investigation. We conducted a comprehensive magnetoencephalography study of connectivity changes in AD and healthy ageing in the resting-state. METHODS: We performed a whole-brain, source-space assessment of oscillatory neural signalling in multiple frequencies comparing AD patients, elderly and young controls. We compared eyes-open and closed group oscillatory envelope activity in networks obtained through temporal independent component analysis, and calculated whole-brain node-based amplitude and phase connectivity. RESULTS: In bilateral parietotemporal areas, oscillatory envelope amplitude increased with healthy ageing, whereas both local amplitude and node-to-global connectivity decreased with AD. AD-related decreases were spatially specific and restricted to the alpha and beta bands. A significant proportion of the variance in areas of peak group difference was explained by cognitive integrity, in addition to group. None of the groups differed in phase connectivity. Results were highly similar for eyes-open and closed resting-state. CONCLUSIONS: These results support the disconnection syndrome hypothesis and suggest that AD shows distinct and unique patterns of disrupted neural functioning, rather than accelerated healthy ageing. SIGNIFICANCE: Whole-brain assessments show that disrupted regional oscillatory envelope amplitude and connectivity in the alpha and beta bands play a key role in AD.

Different trajectories of decline for global form and global motion processing in aging, mild cognitive impairment and Alzheimer's disease.

The visual processing of complex motion is impaired in Alzheimer's disease (AD). However, it is unclear whether these impairments are biased toward the motion stream or part of a general disruption of global visual processing, given some reports of impaired static form processing in AD. Here, for the first time, we directly compared the relative preservation of motion and form systems in AD, mild cognitive impairment, and healthy aging, by measuring coherence thresholds for well-established global rotational motion and static form stimuli known to be of equivalent complexity. Our data confirm a marked motion-processing deficit specific to some AD patients, and greater than any form-processing deficit for this group. In parallel, we identified a more gradual decline in static form recognition, with thresholds raised in mild cognitive impairment patients and slightly further in the AD group compared with controls. We conclude that complex motion processing is more vulnerable to decline in dementia than complex form processing, perhaps owing to greater reliance on long-range neural connections heavily targeted by AD pathology.