Cherie McCracken

Attrition and bias in the MRC cognitive function and ageing study: an epidemiological investigation

BackgroundAny hypothesis in longitudinal studies may be affected by attrition and poor response rates. The MRC Cognitive Function and Ageing study (MRC CFAS) is a population based longitudinal study in five centres with identical methodology in England and Wales each recruiting approximately 2,500 individuals. This paper aims to identify potential biases in the two-year follow-up interviews.MethodsInitial non-response: Those not in the baseline interviews were compared in terms of mortality to those who were in the baseline interviews at the time of the second wave interviews (1993–1996). Longitudinal attrition: Logistic regression analysis was used to examine baseline differences between individuals who took part in the two-year longitudinal wave compared with those who did not.ResultsInitial non-response: Individuals who moved away after sampling but before baseline interview were 1.8 times more likely to die by two years (95% Confidence interval(CI) 1.3–2.4) compared to respondents, after adjusting for age. The refusers had a slightly higher, but similar mortality pattern to responders (Odds ratio 1.2, 95%CI 1.1–1.4).Longitudinal attrition: Predictors for drop out due to death were being older, male, having impaired activities of daily living, poor self-perceived health, poor cognitive ability and smoking. Similarly individuals who refused were more likely to have poor cognitive ability, but had less years of full-time education and were more often living in their own home though less likely to be living alone. There was a higher refusal rate in the rural centres. Individuals who moved away or were uncontactable were more likely to be single, smokers, demented or depressed and were less likely to have moved if in warden-controlled accommodation at baseline.ConclusionsLongitudinal estimation of factors mentioned above could be biased, particularly cognitive ability and estimates of movements from own home to residential homes. However, these differences could also affect other investigations, particularly the estimates of incidence and longitudinal effects of health and psychiatric diseases, where the factors shown here to be associated with attrition are risk factors for the diseases.All longitudinal studies should investigate attrition and this may help with aspects of design and with the analysis of specific hypotheses.

Severity of depression and risk for subsequent dementia: cohort studies in China and the UK

BACKGROUND Depression and dementia often exist concurrently. The associations of depressive syndromes and severity of depression with incident dementia have been little studied. AIMS To determine the effects of depressive syndromes and cases of depression on the risk of incident dementia. METHOD Participants in China and the UK aged > or =65 years without dementia were interviewed using the Geriatric Mental State interview and re-interviewed 1 year later in 1254 Chinese, and 2 and 4 years later in 3341 and 2157 British participants respectively (Ageing in Liverpool Project Health Aspects: part of the Medical Research Council - Cognitive Function and Ageing study). RESULTS Incident dementia was associated with only the most severe depressive syndromes in both Chinese and British participants. The risk of dementia increased, not in the less severe cases of depression but in the most severe cases. The multiple adjusted hazard ratio (HR)=5.44 (95% CI 1.67-17.8) for Chinese participants at 1-year follow-up, and HR=2.47 (95% CI 1.25-4.89) and HR=2.62 (95% CI 1.18-5.80) for British participants at 2- and 4-year follow-up respectively. The effect was greater in younger participants. CONCLUSIONS Only the most severe syndromes and cases of depression are a risk factor for dementia.

THE EARLY ONSET DEMENTIAS: A STUDY OF CLINICAL CHARACTERISTICS AND SERVICE USE

The clinical characteristics and the level of service use were studied in a cohort of 200 patients referred for the investigation of presenile dementia, having had the onset of symptoms before the age of 65. The most common diagnoses given were Alzheimers disease, vascular dementia and depressive pseudodementia. The level of psychiatric morbidity was high, depression insomnia, anxiety and aggression being the most common symptoms. As regards rate of service use, 22% of the Liverpool patients were in residential care after 1 year of follow‐up, in contrast to 8% initially. We conclude that there is a need for specialized multidisciplinary services for this group of patients, both diagnostic and supportive.

Reasons for substance use in dual diagnosis bipolar disorder and substance use disorders: A qualitative study

BACKGROUND Few systematic studies have examined the reasons why patients with bipolar disorder and substance use disorders misuse alcohol and drugs of abuse. Such reasons may depend heavily on context so qualitative research methods that made no prior theoretical assumptions were employed. We explored the reasons patients give for misusing drugs and alcohol and how these relate to their illness course. METHOD Qualitative semi-structured interviews and thematic analysis with a purposive sample of 15 patients with bipolar disorder and a current or past history of drug or alcohol use disorders. RESULTS Patients based their patterns of and reasons for substance use on previous personal experiences rather than other sources of information. Reasons for substance use were idiosyncratic, and were both mood related and unrelated. Contextual factors such as mood, drug and social often modified the patients personal experience of substance use. Five thematic categories emerged: experimenting in the early illness; living with serious mental illness; enjoying the effects of substances; feeling normal; and managing stress. LIMITATIONS The prevalence of these underlying themes was not established and the results may not apply to populations with different cultural norms. CONCLUSIONS Patterns of substance use and reasons for use are idiosyncratic to the individual and evolve through personal experience. Motivating the patient to change their substance use requires an understanding of their previous personal experience of substance use both in relation to the different phases of their bipolar disorder and their wider personal needs.

Does age predict the long-term outcome of depression treated with ECT? (a prospective study of the long-term outcome of ECT-treated depression with respect to age).

Sixty‐three subjects with DSM‐III‐R major depression with melancholia or psychosis were followed up 2–4 years after index treatment with electroconvulsive therapy. There was a twofold increase in likelihood of improved outcome with an additional 20 years of age.

What do medical trainees think is so difficult about communicating with patients

OBJECTIVE To identify the communication skills medical trainees perceive themselves to avoid or use during initial clinical encounters and the areas of communication learning need they identify. METHODS 446 2nd year undergraduate medical students were invited to take part in the study. Details of four encounters with patients were entered into a web-based electronic logbook by the student. Details included perception of use, success and requests for further training from a list of communication process skills. RESULTS 395 (89%) students took part. Factor analysis yielded three types of skills: those used to manage the flow of interaction; the emotional content of the interaction; and structuring the interaction. Skills perceived as being used least often and least successfully and identified by the students as requiring further training were primarily those that involved managing the emotional aspects of interactions with patients rather than managing the flow of information. CONCLUSION Communication training should focus further on the emotional aspects of patient interactions in order to support students during early clinical encounters. PRACTICE IMPLICATIONS Skills required to manage emotional encounters need to be made more explicit to students. Opportunities to obtain feedback and develop competency should be offered as part of the core curriculum.

Challenges of long-term nutrition intervention studies on cognition: discordance between observational and intervention studies of vitamin B12 and cognition

Conducting long-term nutrition intervention studies on cognition can be challenging. The gaps in current methodology are addressed via a case study of the relationship between vitamin B(12) and cognition in people aged 60 and older. There is robust evidence from many observational studies, both cross-sectional and longitudinal, showing that a deficit of the vitamin is associated with poor or declining cognition in this age group, but supplementation of the vitamin in trials does not bring about improved cognition. The evidence from observational studies as well as clinical trials is reviewed here, and the potential difficulties in conducting long-term nutritional intervention studies in this area are highlighted.

APOE and ACE polymorphisms and dementia risk in the older population over prolonged follow-up: 10 years of incidence in the MRC CFA Study

Background: dementia risk conferred by apolipoprotein-E (APOE) and angiotensin-1-converting enzyme (ACE) polymorphisms have been reported for the MRC Cognitive Function and Ageing Study (CFAS) at 6-year follow-up. We concentrate on incident dementia risk over 10 years. Methods: participants come from MRC CFAS, a multi-centre longitudinal population-based study of ageing in England and Wales. Three follow-up waves of data collection were used: 2, 6 and 10 years. Logistic regressions were undertaken to investigate associations between APOE (n = 955) and ACE (n = 856) alleles/genotypes and incident dementia. Two types of control groups were used: non-demented and highly functioning non-demented. Results were back-weighted. Results: compared to APOE ε3, ε2 conferred protection of odds ratio (OR) = 0.3 (95% confidence interval, CI = 0.1–0.6) and ε4 risk of OR = 2.9 (95% CI = 1.7–4.9) for incident dementia. Compared to ε3/ε3, the ε3/ε4 and ε4/ε4 genotypes conferred risks of OR = 3.6 (95% CI = 1.8–7.3) and OR = 7.9 (95% CI = 1.6–39.2), respectively. The ε3/ε2 genotype protected against dementia (OR = 0.2, 95% CI = 0.1–0.7), and ε2/ε2 had a similar protective effect but with wide CIs (OR = 0.3, 95% CI = 0.1–1.7). Restricting the control group accentuated these differentials. The effects of ACE alleles/genotypes on incident dementia risk were small. Conclusions: APOE but not ACE is associated with late-onset incident dementia in the population. Using longer term follow-up with proper adjustment for attrition and incident cases increases estimates of risk.

Biological Variation of Holo-Transcobalamin in Elderly Individuals

Vitamin B12 is a water-soluble molecule essential for mammalian intracellular metabolism. Its two metabolically active forms, methyl-cobalamin and 5-deoxyadenosylcobalamin, are coenzymes in the reactions catalyzed, respectively, by methionine synthase and methylmalonyl-CoA mutase. There are two vitamin B12 carrier proteins in serum, haptocorrin and transcobalamin (TC). Haptocorrin binds the majority of serum B12 but, unlike TC, does not deliver the vitamin to metabolically active cells. Only 5–20% of serum B12 is bound to TC as “holo-TC”. Current laboratory assays determine total serum B12 concentrations and are relatively poor indicators of the ability of serum to deliver the vitamin to tissues. Methods are now available to measure holo-TC in clinical samples (1)(2)(3). Although information exists for “between-person” variations in holo-TC concentrations, (2)(4), very few data exist regarding its “within-person” variability (5). Such knowledge will be essential for studies of diseases potentially associated with low concentrations of holo-TC, such as Alzheimer disease (6). We therefore examined the between- and within-person variability and within-assay variability of holo-TC concentrations in healthy elderly volunteers in the fasting and nonfasting states. The study received local research ethics committee approval and followed an established protocol aimed at minimizing various preanalytical factors that can influence the results of clinical laboratory tests (7). Because valid estimates of the components of variation can be obtained from a relatively small number of participants (7), six males and six females age ≥65 years were recruited. Their mean age was 82.5 years (range, 65–99 years). Ages were not significantly different between males and females (Student t- test, t 10 = 1.4; P = 0.2). The participants were all maintaining their usual lifestyles and not taking any medication. Ten samples of venous blood were collected at 14-day intervals from each participant over a 5-month …

Age-friendly towns and cities: a mixed methods approach to developing an evaluation instrument for public health interventions

Abstract Background In the context of population ageing and urbanisation, a growing number of cities are adopting the WHOs Age-Friendly Cities (AFC) framework, which incorporates eight interlinking domains. This study set out to design an evidence-based instrument to assess interventions intended to make urban settings more age-friendly. Methods Fieldwork is taking place in Liverpool, UK. A needs assessment used census, Hospital Episode Statistics, and Ambulance Service data and highlighted falls as a local health priority for older people (65 years or older). Health, environmental, and social science databases (including PubMed, Scopus, and Web of Science) were systematically searched to identify systematic reviews from Jan 1, 2000, to July 31, 2014, in English that described effective falls-related interventions. Examples of keywords for age were old* people* OR old person* OR age* 65* OR elder*. Examples for review were systematic review* OR narrative review* OR integrated review* OR review*. Examples for falls were fall* OR outdoor safety OR trip hazard*. Interviews with key informants (n=12) from different sectors as well as interviews (n=20) and focus groups (n=2, 10 participants each) with older people on falls-related provision are proceeding. The research is informing the development of an evidence-based evaluation instrument that can be applied to settings and interventions more widely. The instrument will be pilot-tested for usability, with in-depth validation planned for a further project phase. Findings Analysis of available data has shown a high incidence of and case fatality from falls, and it has revealed common causes and locations of falls in Liverpool. The effective falls-related interventions identified were mapped onto the WHO domains to highlight important areas of provision. Strongly represented were interventions that relate well to the domains of Community Support and Health Services and Housing (eg, home modifications). The domains of Outdoor Spaces and Buildings and Transportation were identified as important areas for provision, although the evidence base was more limited. Analysis of qualitative data is exploring whether this pattern is reflected in Liverpools falls-related provision. The evidence mapping, together with the primary data, allows presentation of a picture of strengths and gaps in falls-related provision in Liverpool in relation to the AFC domains. Interpretation Data collection has highlighted key dimensions to be incorporated in the evaluation instrument. These dimensions include consideration of the extent to which AFC initiatives are informed by a needs assessment and robust research evidence, political will, availability of resources, attention to target group perspectives, and plans for evaluation. Funding This project is funded by the National Institute for Health Research School for Public Health Research (SPHR) as part of SPHRs Ageing Well programme of research.