Blossom Christa Maree Stephan

Diagnosing Mild Cognitive Impairment (MCI) in clinical trials: a systematic review

Objective To describe how criteria for amnestic Mild Cognitive Impairment (aMCI) have been operationalised in randomised controlled clinical trials (RCTs). Design Systematic review. Information sources EMBASE, PubMed and PSYCHInfo were searched from their inception to February 2012. Electronic clinical trial registries were also searched (February 2012). Study selection RCTs were included where participant selection was made using Petersen et al-defined aMCI. There was no restriction on intervention type or the outcome tested. Data extraction For each trial, we extracted information on study design, demographics, exclusion criteria and the operationalisation strategy for the five aMCI diagnostic criteria including: (1) memory complaint, (2) normal general cognitive function, (3) memory impairment, (4) no functional impairment and (5) no dementia. Results 223 articles and 278 registered trials were reviewed, of which 22 met inclusion criteria. Various methods were applied for operationalising aMCI criteria resulting in variability in participant selection. Memory complaint and assessment of general cognitive function were the most consistently measured criteria. There was large heterogeneity in the neuropsychological methods used to determine memory impairment. It was not possible to assess the impact of these differences on case selection accuracy for dementia prediction. Further limitations include selective and unclear reporting of how each of the criteria was measured. Conclusions The results highlight the urgent need for a standardised approach to map aMCI. Lack of uniformity in clinical diagnosis, however, is not exclusively a problem for MCI but also for other clinical states such as dementia including Alzheimers disease, Lewy Body, frontotemporal or vascular dementia. Defining a uniform approach to MCI classification, or indeed for any classification concept within the field of dementia, should be a priority if further trials are to be undertaken in the older aged population based on these concepts.

Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS)

Summary Background Little is known about how the proportions of dependency states have changed between generational cohorts of older people. We aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011, and new projections of future demand for care. Methods In this population-based study, we compared two Cognitive Function and Ageing Studies (CFAS I and CFAS II) of older people (aged ≥65 years) who were permanently registered with a general practice in three defined geographical areas (Cambridgeshire, Newcastle, and Nottingham; UK). These studies were done two decades apart (1991 and 2011). General practices provided lists of individuals to be contacted and were asked to exclude those who had died or might die over the next month. Baseline interviews were done in the community and care homes. Participants were stratified by age, and interviews occurred only after written informed consent was obtained. Information collected included basic sociodemographics, cognitive status, urinary incontinence, and self-reported ability to do activities of daily living. CFAS I was assigned as the 1991 cohort and CFAS II as the 2011 cohort, and both studies provided prevalence estimates of dependency in four states: high dependency (24-h care), medium dependency (daily care), low dependency (less than daily), and independent. Years in each dependency state were calculated by Sullivans method. To project future demands for social care, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections. Findings Between 1991 and 2011, there were significant increases in years lived from age 65 years with low dependency (1·7 years [95% CI 1·0–2·4] for men and 2·4 years [1·8–3·1] for women) and increases with high dependency (0·9 years [0·2–1·7] for men and 1·3 years [0·5–2·1] for women). The majority of mens extra years of life were spent independent (36·3%) or with low dependency (36·3%) whereas for women the majority were spent with low dependency (58·0%), and only 4·8% were independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71 215 care home places by 2025. Interpretation On average older men now spend 2·4 years and women 3·0 years with substantial care needs, and most will live in the community. These findings have considerable implications for families of older people who provide the majority of unpaid care, but the findings also provide valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations. Funding Medical Research Council (G9901400) and (G06010220), with support from the National Institute for Health Research Comprehensive Local research networks in West Anglia and Trent, UK, and Neurodegenerative Disease Research Network in Newcastle, UK.

Aberrant pattern of scanning in prosopagnosia reflects impaired face processing.

Visual scanpath recording was used to investigate the information processing strategies used by a prosopagnosic patient, SC, when viewing faces. Compared to controls, SC showed an aberrant pattern of scanning, directing attention away from the internal configuration of facial features (eyes, nose) towards peripheral regions (hair, forehead) of the face. The results suggest that SCs face recognition deficit can be linked to an inability to assemble an accurate and unified face percept due to an abnormal allocation of attention away from the internal face region. Extraction of stimulus attributes necessary for face identity recognition is compromised by an aberrant face scanning pattern.

Predicting risk of 2-year incident dementia using the CAMCOG total and subscale scores

BACKGROUND being able to identify individuals at high risk of dementia is important for diagnostics and intervention. Currently, there is no standard approach to assessing cognitive function in older aged individuals to best predict incident dementia. OBJECTIVE to identify cognitive changes associated with an increased risk of 2-year incident dementia using the Cambridge Cognitive Examination (CAMCOG). DESIGN longitudinal population representative sample aged 65+ years. METHODS individuals were from the Medical Research Council Cognitive Function and Ageing Study. Classification and Regression Tree analysis was used to detect the optimal cut-off value for the CAMCOG total, subscales and composite memory and non-memory scores, for predicting dementia. Sensitivity and specificity of each cut-off score were assessed. RESULTS from the 2,053 individuals without dementia at the first assessment, 137 developed dementia at the 2-year follow-up. The results indicate similar discriminative accuracy for incident dementia based on the CAMCOG total, memory subscale and composite scores. However, sensitivity and specificity of cut-off values were generally moderate. Scores on the non-memory subscales generally had high sensitivity but low specificity. Compared with the CAMCOG total score they had significantly lower discriminative accuracy. CONCLUSION in a population setting, cut-off scores from the CAMCOG memory subscales predicted dementia with reasonable accuracy. Scores on the non-memory scales have lower accuracy and are not recommend for predicting high-risk cases unless all non-memory subdomain scores are combined. The added value of cognition when assessed using the CAMCOG to other risk factors (e.g. health and genetics) should be tested within a risk prediction framework.

Neuropsychological profiles of vascular disease and risk of dementia: implications for defining vascular cognitive impairment no dementia (VCI-ND)

Background vascular cognitive impairment no dementia (VCI-ND) defines a preclinical phase of cognitive decline associated with vascular disorders. The neuropsychological profile of VCI-ND may vary according to different vascular conditions. Objective to determine the neuropsychological profile of individuals with no dementia and vascular disorders, including hypertension, peripheral vascular disease (PVD), coronary heart disease (CHD), diabetes and stroke. Risk of 2-year incident dementia in individuals with disease and cognitive impairment was also tested. Methods participants were from the Cognitive Function and Ageing Study. At baseline, 13,004 individuals aged ≥65 years were enrolled into the study. Individuals were grouped by baseline disorder status (present, absent) for each condition. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG). Dementia was assessed at 2 years. Results in the cross-sectional analysis, hypertension, PVD and CHD were not associated with cognitive impairment. Stroke was associated with impaired global (MMSE) and CAMCOG sub-scale (including memory and non-memory) scores. Diabetes was associated with impairments in global cognitive function (MMSE) and abstract thinking. In the longitudinal analysis, cognitive impairments were associated with incident dementia in all groups. Conclusion the neuropsychological profile in individuals with vascular disorders depends on the specific condition investigated. In all conditions cognitive impairment is a risk factor for dementia. A better understanding of which cognitive domains are affected in different disease groups could help improve operationalisation of the neuropsychological criteria for VCI-ND and could also aid with the development of dementia risk prediction models in persons with vascular disease.

Can we influence the epidemiology of dementia? Perspectives from population-based studies

The worldwide prevalence of dementia is predicted to rise significantly in the next three decades. However, these projections have not taken into account the role of modifiable risk factors and whether any prevention strategies might influence the predicted trend. Attempts at pharmacological disease modification have largely been disappointing, and the difficulties in conducting dementia trials are reviewed here. In contrast, recent population studies in high-income countries suggest that the epidemiology may be changing with a possible decline in incident dementia, or even a reduction in age-specific prevalence. Therefore, efforts to develop public health interventions may prove to be the more successful approach to addressing dementia at a societal level.

Models for Predicting Risk of Dementia: Predictive Accuracy and Model Complexity

As strategies to prevent dementia or delay disease progression are developed, it will be important to have risk prediction models to prioritize and target intervention to high-risk individuals. Targeting whole populations is not always cost-effective, particularly when intervention strategies are expensive or adherence rates are low. A complementary approach may be to develop a prediction algorithm to identify individuals at highest risk of dementia as early as possible without being too broad in risk selection. This chapter will present an overview of existing dementia risk prediction models with a focus on their predictive accuracy (e.g., sensitivity, specificity and discrimination), the types of variables incorporated (e.g., cognitive, neuroimaging, genetics and health assessment) and the cost of attaining the risk score (e.g., in terms of equipment and the need for specialist training for risk score attainment). A better understanding of available dementia risk models and their predictive accuracy has implications for improving diagnostics, targeting services and undertaking of more focused risk factor reduction in older aged populations.

Gaps in care for patients with memory deficits after stroke: views of healthcare providers

BackgroundStroke is a common cause of physical disability but is also strongly associated with cognitive impairment and a risk for future dementia. Despite national clinical guidelines, the service provided for stroke survivors with cognitive and memory difficulties varies across localities. This study critically evaluated the views of healthcare professionals about barriers and facilitators to their care.MethodsSeventeen semi-structured individual interviews were conducted by a single interviewer with both primary and secondary care clinicians in regular contact with stroke-survivors. This included stroke medicine specialists, specialist nurses, physiotherapists, occupational therapists, general practitioners and primary care nurses. Topics included individual experiences of the current care offered to patients with cognitive impairment, assessment processes and inter-professional communication. Interviews were audio recorded and transcribed verbatim. Transcripts were thematically analysed and themes grouped into broad categories to facilitate interpretation.ResultsData analysis identified four key themes as barriers to optimal care for stroke-survivors with memory difficulties: 1) Less focus on memory and cognition in post-stroke care; 2) Difficulties bringing up memory and cognitive problems post-stroke; 3) Lack of clarity in current services; and, 4) Assumptions made by healthcare professionals introducing gaps in care. Facilitators included stronger links between primary and secondary care in addition to information provision at all stages of care.ConclusionsThe care provided by stroke services is dominated by physical impairments. Clinicians are unsure who should take responsibility for follow-up of patients with cognitive problems. This is made even more difficult by the lack of experience in assessment and stigma surrounding potential diagnoses associated with these deficits. Service development should focus on increased cohesiveness between hospital and community care to create a clear care pathway for post-stroke cognitive impairment.