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Diseases and Impairments as Risk Factors for Onset of Disability in the Older Population in England and Wales: Findings From the Medical Research Council Cognitive Function and Ageing Study

¹ Department of Health Sciences
² Department of Cardiovascular Sciences, University of Leicester, United Kingdom.
³ Medical Research Council Biostatistics Unit
⁵ Lipitz Center for Integrated Health Care, The Johns Hopkins University, Baltimore, Maryland.

Carol Brayne^4,

⁴ Institute of Public Health, University of Cambridge, United Kingdom.

Address correspondence to Dr. Nicola Spiers, Department of Epidemiology and Public Health, University of Leicester, 22-28 Princess Road West, Leicester, LE1 6TP. E-mail: nas6{at}le.ac.uk

Address correspondence for the Medical Research Council Cognitive Function and Ageing Study to Professor C. Brayne, Institute of Public Health, Forvie Site, Robinson Way, Cambridge CB2 2SR.

	Abstract

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Background. This paper reports the association between self-reported diseases and impairments and 2-year onset of disability in a prospective study of people aged 65 years or older in five urban and rural centers in England and Wales (Medical Research Council Cognitive Function and Ageing Study; MRC-CFAS).

Methods. We initially reviewed risk factors for onset of disability in 35 prospective studies of functional decline in older people published in 1998–2001. In the present study, disability was defined as requiring help from another person at least several times a week and was assessed by dependency in activities of daily living. Polytomous and bivariate logistic regression models were fitted for onset of disability and mortality among those nondisabled at baseline (n = 7913), adjusting for age, sex, and sociodemography.

Results. Among prevalent conditions, arthritis (population-attributable risk 11.4%) and cognitive impairment indicated by a Mini-Mental State Examination score of 21 (population-attributable risk 6.8%) were powerful predictors of incident disability. Baseline cognitive impairment, stroke, treated diabetes, chronic airways obstruction, coronary heart disease, and treated hypertension were significantly associated with both incident disability and mortality, whereas Parkinson's disease, eyesight problems, and arthritis were statistically significant disabling conditions not associated with mortality. Stroke, heart attack, cognitive impairment, eyesight problems, and hearing problems were newly occurring conditions significantly associated with onset of disability.

Conclusions. Cognitive impairment, arthritis, followed by stroke, and problems with vision have major impact on population disability at older ages. Both prevalent and incident conditions must be considered as risk factors to accurately assess potential benefits from prevention.

	SYSTEMATIC REVIEW OF PROSPECTIVE RISK FACTORS FOR FUNCTIONAL DECLINE IN COMMUNITY-BASED STUDIES, 1998–2001

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As a precursor to the present study, we updated the earlier systematic review, using similar search terms, but restricting the focus to articles published in English and French between 1998 and 2001 inclusive and reporting a prospective measure of association of functional status with a specific disease or chronic condition as a risk factor. Of a total of 35 published analyses on 27 databases that met our criteria for inclusion, 11 identified general risk factors for functional decline, 3 evaluated a list of diseases or conditions, 15 focused on a particular condition (9 on depression/affect, 2 on musculoskeletal conditions, 1 on sensory impairments, and 2 on cognitive status), and 6 focused on another specific risk factor (for example, physical fitness) but reported at least one association with a disease or condition. There were no studies published in French that met our inclusion criteria.

Findings from the 27 databases are summarized in Table 1. Conclusions should be drawn with care, as the significance of associations depends on sample size, the measure of functional decline, covariates adjusted for, and how the risk factor was elicited. Despite these cautions, there is some consistency in the evidence linking depression and cognitive impairment with functional decline, partially reflecting the number of large studies focusing on these conditions. Less consistent are findings for arthritis, diabetes, and respiratory disease, which may reflect differences in definition between databases.

Community-based evidence on diseases as predictors of functional decline in the United Kingdom is restricted to the London studies (5), with focus limited to depression, anxiety, and musculoskeletal problems. The MRC-CFAS is the first study from the United Kingdom with sufficient power to look at both prevalent and incident conditions as risk factors for onset of disability, and to include rare conditions such as Parkinson's disease.

	METHODS FOR MRC-CFAS ANALYSIS

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A full description of the MRC-CFAS study design can be found elsewhere (6). For the initial screen, random samples of people aged 65 years or older were selected from the National Health Service primary care lists. Name, address, sex, date of birth, and National Health Service number were extracted from computerized lists held by the Family Health Service Authority at four centers. In the fifth center (Gwynedd), the data were obtained manually from general practices. Individuals in long-stay hospitals remain registered with their general practioner and were recorded as such for at least 2 years after institutionalization, so the sampling method ensures their inclusion. Those aged 75 years or over were oversampled.

All participants were initially screened at their place of residence from 1991 through 1994 by trained interviewers who followed a computerized, structured interview enquiring about sociodemography, general health (including chronic conditions), cognition, smoking, and ADLs. Surviving participants were interviewed again 2 years later regarding their health and ADLs, either at an incidence screen that was essentially similar to the initial interview, or at a more detailed cognitive assessment.

We used the MRC-CFAS data set version 6.1 for this analysis, which has information on 13,004 people who took part in the initial screen in three urban (Newcastle, Nottingham, and Oxford) and two rural centers (Cambridgeshire and Gwynedd, Wales) and the 2-year follow-up.

Measurement of Onset of Disability
The interviews included items from the modified Townsend ADL scale (7), covering the participant's ability to perform nine activities and tasks, including eight ADLs/instrumental ADLs. The root question was "Are you able to ...?" and response categories were "yes, with no difficulty," "yes, with some difficulty," and "no, needs help." If an activity was not normally undertaken, probing was used to establish whether the participant would be able to undertake the activity in the absence of another person. Participants' mobility was also rated by the interviewer as usually ambulant nonhousebound, usually ambulant housebound, chairfast permanently, and bedfast permanently.

Using information on the hierarchy of ADL/instrumental ADL (1) and on the basis of the concept of interval of need (8), we classified participants as disabled if they were unable to perform at least one of the following five ADLs without human help: transfer to and from a chair, put on shoes and socks, prepare a hot meal, get around outside, and have a bath or an all-over wash. The participants classified as disabled are considered as requiring help at least several times a week. Our threshold is slightly more inclusive than that used by Boult and colleagues in their analysis of onset of disability in the Longitudinal Study of Aging (9).

Measurement of Risk Factors
At baseline, participants were asked if they had ever suffered from heart attack, angina, intermittent claudication, diabetes, asthma, chronic bronchitis, arthritis, Parkinson's disease, treated hypertension, stroke, emotional problems, or underactive thyroid. Angina and peripheral vascular disease (PVD; intermittent claudication) were elicited from the Rose scales (10). Participants were considered to have coronary heart disease if they reported having suffered from a heart attack or angina, or were classified as having angina from the Rose angina scale. Participants were classified as having chronic airways obstruction if they had suffered from chronic bronchitis or asthma (excluding childhood asthma). Treated diabetes was coded in participants who reported receiving treatment currently for their diabetes; treated hypertension was handled similarly.

Participants were classified as having had a stroke if they answered positively to the question "Have you ever had a stroke that required medical attention?" and reported that the stroke was diagnosed by a general practitioner or specialist. Participants were asked whether they had ever consulted a doctor about emotional problems or problems with nerves. Those who responded positively to this question, and who also reported that the doctor said they had depression or manic depression, were considered to have had depression. Participants were considered to have hearing or eyesight problems if (a) they reported suffering from poor hearing or eyesight that interfered with day-to-day living or (b) the interviewer observed problems that interfered to a marked extent with the interview process. Participants with negative self-report but interviewer-observed sensory limitations were rare (n = 6 for eyesight and n = 10 for hearing limitations). Cognitive impairment was assessed using the Mini-Mental State Examination (MMSE) (11). Missing items were divided according to their nature. Answers of "Don't know" or "no answer," and items which could not be answered due to sensory or mobility problems, were recoded to zero. For all other missing items, the full score was recoded to missing, unless the individual could be assigned to an MMSE category unambiguously on the basis of completed items.

Methods of eliciting diseases and conditions were similar at baseline and 2-year follow-up, except that single questions eliciting similar information were substituted for the angina and intermittent claudication scales for those participants who had a more detailed cognitive assessment at follow-up (n = 1185). This substitution may have resulted in some underascertainment of incident angina and PVD. Participants who reported disease in the past 2 years at follow-up but no disease at baseline were regarded as having incident disease.

Statistical Analysis
A polytomous regression model using STATA (12) was used to estimate separate risk factors for onset of functional limitation and death in those not disabled at baseline (Appendix). The initial backward stepwise modeling process included all of the prevalent chronic conditions at baseline as predictors plus indicator variables for age group and sex. To ensure that associations were not overstated due to confounding with sociodemography and lifestyle, a second model was fitted, additionally forcing educational level, living status, social class, and smoking status into the model. The criteria for retention of chronic conditions was significance of regression coefficients for onset of disability or mortality at p =.1. Two-factor interactions between chronic conditions and between conditions and sociodemographic variables were considered where there was a plausible clinical pretext. All two-factor interactions with age were examined, and interactions were added to the model in turn, using the likelihood ratio test to assess significance (p <.05).

Incident conditions were not included as risk factors in the initial modeling process, to avoid overestimating associations due to disease following onset of disability. However, because we examined onset in a cohort with no disability at baseline, the model with prevalent conditions understates the impact of associations between disability and conditions such as cerebrovascular disease, the onset of which is often silent until a catastrophic event. For example, those in the analysis cohort who reported stroke must have had either a mild stroke or a more severe stroke with good recovery (13). To gain a more complete view of the role of diseases in onset of disability, a bivariable logistic regression model for onset of disability among those initially without disability and surviving 2 years was also fitted. For each condition, indicator variables were entered for prevalent disease (disease reported at baseline, regardless of reports at 2-year follow-up) and incident disease (disease not reported at baseline, but reported at 2 years). Thus the reference group for each condition is those who survived and never reported the disease. Heart attack and angina were entered as separate risk factors in this model. The Rose scales for angina and PVD had relatively high levels of missing incidence data (8.8% and 5.0%, respectively, of those independent at baseline with functional status assessed at follow-up), probably due to their being subscales rather than single-item responses. A missing category was included in the model for these diseases.

Population-attributable risks were calculated as the percentage of the total disability predicted by the final model that was removed when predicted outcomes at 2 years were recalculated for the population with the given disease coded as absent for all participants. To adjust for oversampling of those aged 75 years or older, responses were reweighted by age and sex to reflect the population age distribution at each of the five centers. Results from models using weights are presented.

	RESULTS

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The response rate for the initial screen was over 80% overall. Of 13,004 participants interviewed (MRC-CFAS data set release 6.1), 12,841 people (98.7%) provided sufficient data for their functional status to be classified at baseline. Of these, 235 participants failed to show that they were oriented in time and space, after initial questions at baseline. These participants were classified as disabled, as it was unlikely that they would be able to prepare or cook a hot meal. A small number of participants with missing data on one or more of the five ADLs were classified as not disabled on the basis of additional ADL information from the Townsend scale.

At baseline, 2259 participants were disabled, of whom 609 (27.0%) died, 812 (36.0%) were alive and disabled at follow-up, and 223 (9.9%) were alive and not disabled at follow-up. Because of the small number with improved functional status and relatively high loss to follow-up (27.2%, n = 615 of 2259 who were disabled at baseline), risk factors for improvement were not investigated.

The 10,582 people who were not disabled at baseline formed the study cohort for investigation of risk factors for onset of disability. A total of 8142 (76.9%) were successfully followed up for functional status at 2 years, including 6753 (63.8%) who were not disabled at 2 years, 685 (6.5%) who were disabled, and 704 (6.6%) who died. The majority of remaining participants did not receive a follow-up interview through refusal (20.1%, n = 2122) or because they had moved away from the study area (1.5%, n = 154), but 1.6% (n = 164) were unclassifiable at follow-up due to missing data on ADLs.

Members of the cohort who were lost to follow-up after the baseline screen had similar prevalence of all chronic conditions at baseline to those analyzed (Table 2). However, they were more likely to score as cognitively impaired on the MMSE at baseline and had fewer years of education.

Arthritis and hearing and eyesight problems were the most common incident conditions (Table 4). When incident and prevalent conditions are included in a model for onset of disability among survivors, the pattern of associations for prevalent conditions is largely unchanged. However, there are additionally very strong associations (odds ratio > 3.0) between onset of disability and incident moderate cognitive impairment, stroke, and Parkinson's disease, as well as significant associations with heart attack and incident eyesight problems. Incident angina was associated with a lower risk of onset of disability.

View larger version (30K): [in this window] [in a new window]   Figure 1. Population-attributable risk of disability onset: effect of including incident conditions in risk factor model. CAO = Chronic airways obstruction; MMSE = Mini-Mental State Examination; CHD = coronary heart disease. Population attributable risks for hearing problems and PVD are based on nonsignificant associations

	DISCUSSION

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The findings for cognitive impairment confirm other studies that have shown a strong association between cognitive impairment and subsequent ADL disability (3,14,15). Because the MRC-CFAS focused on cognitive decline, every effort was made to maximize valid response on physical function, diseases, and impairments from those with cognitive impairment, including use of proxy responses (n = 20 among those nondisabled at baseline). Among those with no disability at baseline, 58 (0.6%) were excluded from the estimation sample because of missing MMSE score at baseline, 7345 scored 26–30 at baseline, of whom 83% were successfully followed up for disability (including deaths), 2425 scored 22–25, of whom 68% were successfully followed up, and 754 scored 21, 38% of whom were followed up. It is likely that the association between cognitive impairment and disability is understated due to these losses: In a boundary case sensitivity analysis (in which all losses were assumed to have become disabled), the odds ratio for prevalent cognitive impairment increased from 3.4 to 6.2.

The high prevalence of self-reported arthritis in this population is consistent with that in other surveys (16,17), although the validity of responses to the question "Have you ever suffered from arthritis?" is open to question (18,19). The association between arthritis and onset of disability is statistically significant in some studies, but not in others (Table 1). Nevertheless, the high population burden of disability attributable to arthritis in our data and also in data from the U.S. Longitudinal Study of Aging (9) underlines the usefulness of recent studies with more detailed measurement of joint impairment—both in population-based surveys of disability in the older population (20) and in those studies which also take severity into account (21).

The MRC-CFAS is a unique source of data on chronic disease and disability onset in the United Kingdom. There is evidence for the validity of UK self-report data on some diseases and conditions (22), but the uncertain validity of other self-reported diagnostic data suggests caution in interpretation. The lack of an association between prevalent depression and onset of disability could be due to the measure of depression at baseline, which included any past episode. Incident depression was significantly associated with onset of disability when adjusted for age and sex only, but not in the model with all diseases.

The pattern of associations identified may be affected by lack of measurement of fractures, osteoporosis, and cancer, which are not available in CFAS, and by incomplete ascertainment of congestive heart failure. The associations studied are a product of medical knowledge, with focus on cognitive decline in the early 1990s. Although more detailed measures of lifestyle and socioeconomic status would be desirable, adjustment for those measures available had a very limited effect on the disease-disability pathway. This finding is consistent with that of Melzer and coworkers (23), who found that socioeconomics had limited bearing on the disablement process subsequent to the initial onset of mobility disability.

This study confirms evidence from the EPESE (3) database that incident heart attack, and especially stroke are strongly associated with onset of disability in those persons aged 65 years or older. The association of ADL disability with incident diabetes in the U.S. data is not confirmed here, using treated disease as the threshold. This finding may reflect time lapse of more than 2 years between initial treatment and onset of disability, and the shorter follow-up here, compared to that in the EPESE. We present new evidence that incident eyesight problems and Parkinson's disease are associated with onset of disability. In the case of both eyesight and hearing, incident problems are more closely associated with onset of disability than are problems reported at baseline.

If incident conditions are omitted, the impact of cognitive impairment, stroke, heart attack, and sensory problems as risk factors for ADL onset of disability is understated, but caution is required in interpreting the model with incident conditions as there are just two measurement occasions. Where the disease–impairment–disability continuum is well-established, for example, with stroke and sensory impairments, it may be reasonable to assume that disease preceded disability. In others, however, the strength of association with onset of disability may be overstated due to reverse causation. For example, onset of disability may accelerate cognitive decline, if it results in disengagement of individuals from their customary social networks (24).

Despite these caveats, including incident conditions in our model has provided new evidence allowing us to represent more accurately the relative importance of cognitive impairment, stroke, and eyesight problems in the pathway to disability at population level. The results underline the importance of accounting beyond individual disease entities in assessment of preventive interventions. Each of the models presented here has deficits, but they are complementary in that information from both must be synthesized, if the potential benefits of treatments and interventions to prevent disability are to be accurately weighed.

	APPENDIX

Top Abstract Systematic Review of Prospective... Methods for MRC-CFAS Analysis Results Discussion Appendix References

 
Outcome Y takes values 1 = not disabled, 2 = disabled, 3 = dead.

p_ij is the probability that the ith observation is in category j at 2-year follow-up.

x_i ... x_k are covariate vectors.

	Acknowledgments

 
We are grateful for the cooperation of the Family Health Service Authorities at each center, local general practitioners, and their staff. We are indebted to Gillian Parker, Michael Dewey, and Tony Johnson for advice; to Barbara Davidson for clerical support; and to Mark Hibbett for assistance with databases. Thanks are especially due to the residents of East Cambridgeshire, Ynys Mon, Dwyfor, Newcastle upon Tyne, Nottingham, and Oxford for their continuing participation in the study.

	Footnotes

 
This study is funded by the Health Foundation. MRC-CFAS has been supported by major awards from the Medical Research Council and the Department of Health and is currently an MRC Co-operative.

Decision Editor: John E. Morley, MB, BCh

Received July 9, 2003

Accepted October 15, 2003

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