INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, VOL. 9: 11-15 (1994)

DEMENTIA IN A BRITISH RISK FACTORS AMONG INCIDENT CASES OF

REPRESENTATIVE SAMPLE

KEVIN MORGAN* AND JEANETTE M. LILLEY? *Lecturer, ?Research Oficer, Department of Health Care of the Elderly, University of Nottingham Medical School,

Nottingham NG7 2UH, UK

SUMMARY

In a 4-year follow up of 1042 elderly people (aged 65 +) randomly sampled from the community, levels of dementia were assessed using a two-phase case-finding procedure (screening followed by clinical interview) among survivors, with additional information provided by death certificates, hospital case notes or postal questionnaires. Overall, 42 cases were clinically identified. In a case-control analysis matching for age, sex and premorbid cognitive status, risk estimates were obtained for nine self-reported factors: heart trouble; headaches; giddiness; falls; current smoking; past smoking; left-handedness; insomnia; and the use of sedative-hypnotic drugs to promote sleep. While none of these factors was associated with a significantly increased risk, the power of these case-control comparisons was limited by sample size.

KEY woms-Elderly, epidemiology, dementia, longitudinal study, risk factors.

While the present literature is inconclusive regard- ing likely risk factors for dementing illness, recent studies have identified factors which clearly merit research attention. In a detailed review Jorm (1990), for example, lists 41 factors which have been investigated as possible risks for Alzheimer’s dis- ease and concludes that only three-Down’s syn- drome, familial dementia and old age itself-are ‘confirmed’ risk factors. Nevertheless, reflecting the breadth of epidemiological interests shown in this topic, Jorm (1990) lists a further 20 factors ‘needing further investigation’, and a further 16 factors ‘unlikely’ to be associated with significantly increased risk.

Possibly contributing to uncertain or equivocal results are the wide variations in data type, statisti- cal approach and sample size found in the epide- miological literature. Recent studies have variously employed cross-sectional (eg Dewey et al., 1988; Baker et al., 1993) and longitudinal (Herbert et al., 1992) data, multiple (Dewey et al., 1988; Herbert et al., 1992) and single (Baker et al., 1993) controls per case, and sample sizes (of cases) ranging from 36 (Baker et al., 1993), through 56 (Dewey et al., 1988) to 76 (Herbert et al., 1992). Few studies, how- ever, have used incident cases matched with con- trols. Using premorbid information collected in the

course of a longitudinal study, the present analyses estimated the risk associated with selected personal, health and lifestyle characteristics in 42 incident cases of dementia matched with 42 controls.

METHOD

The 1985 survey The Nottingham Longitudinal Study of Activity

and Ageing (NLSAA) was set up in 1983 to assess the role of lifestyle and customary physical activity in promoting and maintaining mental health and psychological well-being in later life. The first population survey was conducted between May and September 1985, during which time 1042 peo- ple randomly sampled from Family Practitioner Committee lists, and demographically representa- tive of the British elderly population, were inter- viewed in their own homes. Within the survey sample, those aged 75 + were intentionally over- represented in order to admit sufficient numbers for subsequent longitudinal analyses. Thus, while the ratio of ‘old’ (65-74 years) to ‘very old’ (75+ years) people in the British population was, in 1985, approximately 1.62: 1 (OPCS, 1983), a baseline

0885-6230/94/0 1001 1 -O5$07.50 0 1994 by John Wiley & Sons, Ltd,

Received 22 February 1993 Accepted 26 July 1993

12 K . MORGAN A N D J . M . LILLEY

ratio of 1 : 1 was aimed for in this study. In estimat- ing incidence for the whole sample, therefore, the over-represented 75 + group was appropriately weighted (by a factor of 0.6) so that the age struc- ture of the combined subsamples approximated that of a true random sample.

Cognitive status was assessed using the 12-item Information/Orientation (I/O) subscale from the Clifton Assessment Procedures for the Elderly (CAPE; Pattie and Gilleard, 1979). The score ranges 0-7,8-9, 10-12 were used to classify respon- dents as impaired, borderline impaired, and unim- paired, respectively. This classification was then validated against clinical diagnostic ratings (see Morgan et al., 1987). Briefly, three subgroups were randomly selected from all three classes ( N = 20 ‘impaired’; N = 14 ‘borderline’; N = 20 ‘unim- paired’). For the ‘unimpaired’ group, individuals were matched for age (+ 5 years) and sex with the ‘impaired’ group. Respondents thus selected were then visited at home and clinically assessed by an experienced psychogeriatrician who was blind to the survey classification. On the basis of clinical judgement, evidence for dementia was then rated by each clinician on a four-part scale as follows: 0-no evidence; 1-a little evidence; 2-a lot of evidence; 3-outstanding evidence. If appropriate, ratings of severity (1-mild; 2-moderate; 3- severe) were then made. This procedure was con- ducted within 12 weeks of the original interview and showed 92% agreement between survey and clinician’s ratings (kappa = 0 . 8 3 ; ~ < 0.001). Given that the aim of this exercise was to assess only the validity of judgement made on the basis of a rating scale administered by lay interviewers, no emphasis was placed on discriminating between vascular and Alzheimer-type dementias.

The 1989 survey

The first complete follow-up of survivors was conducted between May and September 1989. All respondents who had participated in 1985, and who were still living in Nottingham, were invited to par- ticipate in the follow-up study. Attrition from the originally interviewed sample is shown in Table 1. Overall, 781 individuals from the original sample were available for follow-up interviews and of these, 690 agreed to be reinterviewed (a follow-up response rate of 88%). Information on respondents who had died since 1985 was provided by the Natio- nal Health Service (NHS) central register, general practitioners’ records and hospital case notes.

Information on respondents who had moved within, or migrated out of the study area was pro- vided by general practitioners, the Family Health Services Authority (formerly the Family Practi- tioner Committee), the NHS central register, the local authority and, where appropriate, local social networks. For the purposes of identifying incident cases between 1985 and 1989, the population at risk was defined as those respondents for whom there existed clear evidence of non-impairment in 1985 ( N = 970). Specifically excluded from the ori- ginal sample of 1042, therefore, were those respon- dents with I/O scores I 9 and those with incomplete I/O scores.

Table I . NLSAA attrition from original sample. Sample details

No. of respondents interviewed in 1985 1042 Successful interviews in 1989 690

Losses between 1985 and 1989 (total= 352) Deaths 26 I Untraceable 25 Refusals 63 Emigration 3

Of those scoring I 9 on CAPE I10 Clinically assessed Diagnosed through medical records

37 13

Total 50

The questionnaire used in the follow-up was similar to that employed in 1985, and covered aspects of health, lifestyle and physical activity. As in 1985, cognitive status was assessed using the 12- item CAPE Information/Orientation (I/O) subs- cale. All respondents with an I/O score of 1 9 were selected for clinical diagnostic assessments conducted &12 weeks after the screening interview. These assessments were again conducted by experi- enced psychogeriatricians who were blind to the I/O scores. Evidence for dementia was rated on a four-part scale (0-no evidence; 1-a little evi- dence; 2-a lot of evidence; 3-outstanding evi- dence). If appropriate, ratings of severity (1-mild; 2-moderate; 3-severe) were then made. In the findings reported here, clinician-rated dementia refers to undifferentiated dementing illness of at least moderate severity meeting DSM-111-R criteria (American Psychiatric Association, 1987). Respon- dents who had died since the 1985 interview were classified dementedhowdemented on the basis of

RISK FACTORS FOR DEMENTIA 13

Table 2. Factors* included in risk analyses

Factor as described at interview Factor as operationally defined

Heart trouble

Handedness Giddiness

Fallen in past year Headaches Current smoker Ever smoked Insomnia Hypnotic use Other sleep medicine

Self-reported angina, MI, valve disease, rheumatic heart disease, pal- pitations

Preferred hand Self-reported feelings of being ‘wobbly’, dizzy spells, giddiness asso-

Fall (in the past year) from an upright position Migraines, neuralgia, sinusitis, etc Current cigarette, cigar or pipe smoker Past cigarette, cigar or pipe smoking Reported problems sleeping at least ‘sometimes’ Using prescribed sedative medication to promote sleep Using non-sedative medicines (mainly non-prescription analgesics) to

ciated with postural hypotension

use oromote sleeD

~

*All factors recorded 4 years prior to the identification of incident cases.

death certificate information or, where available, hospital case notes.

disturbance not only accompanies but migh predict dementia onset is untested.

also

Risk factors The risks associated with nine personal, health

and lifestyle factors were considered. Two of these (left-handedness and heart disease) are among those listed by Jorm (1990) as ‘needing further investigation’. A further two factors (giddiness and falls) were included to assess the possibility that these not uncommon events in later life (see Blake et al., 1988) may, in some cases, indicate prodromal CNS symptoms of dementia. A history of hea- daches was included specifically to reassess the findings of Dewey et al., (1988), who found that the symptom of headache ‘in the past month’ was associated with a significantly reduced risk of dementia. Two items on smoking were also included to examine further a cross-sectional find- ing from the Nottingham data (Ebrahim et a/., 1988), and supported by subsequent US findings (Grossberg et al., 1989), that cognitive impairment was significantly more common among non- smokers. Finally, two factors indicative of sleep disturbance were also included; insomnia (applied to those who experienced ‘. . . problems sleeping’ at least sometimes); and hypnotic use (applied to those who, in answer to the question ‘Do you take any medicines to help you get to sleep’ reported the use of prescription drugs with known sedative- hypnotic properties). While profound sleep distur- bance is now a widely recognized feature of the dementia syndrome (see Prinz et al., 1982; Allen et al., 1987), the possibility that subjective sleep

Case-control procedures Once identified, each case was matched with a

control on the basis of age (& 1 year), sex and CAPE score in 1985 (& 1 point). All controls were respondents drawn from the NLSAA. For those respondents who had been classified postmortem from hospital records, controls were also matched on year of death. The statistical power of each case- control analysis, based on relative risk estimates with 1:l matching at the 5% level of significance, was assessed using the tables of Breslow and Day (1987). Statistical comparisons for each of the selected risk factors were made using Mantel- Haenszel risk estimates for matched pairs, followed by McNemar’s test of significance (Fleiss, 1973). The nine factors analysed in this way are described in Table 2.

RESULTS

Population at risk Early analyses examined the fate of those respon-

dents excluded from the population at risk on the basis of ‘borderline’ I/O scores (ie those in the range 8-9) in 1985. Of 22 ‘borderline’ cases identified in 1985, 11 (50%) had died before rescreening in 1989, a 4-year mortality rate similar to that found among the ‘impaired’ (53%), but significantly higher than that found among the ‘unimpaired’

14 K. MORGAN AND J . M. LILLEY

Table 3. Mantel-Haenszel risk estimation with 1: 1 matching

Exposed (N) Man tel-Haenszel 95% confidence risk estimate limits

Case Control Lower Upper P*

Heart trouble 11 5 2.20 0.79 6.16 0.21 Not right-handed 2 2 Numbers too small-test invalid Giddiness 1 1 11 1 .oo 0.00 0.00 0.83 Fallen in past year 10 4 2.50 0.82 7.66 0.18 Headaches 10 6 1.67 0.61 4.54 0.45

Ever smoked 9 4 2.25 0.72 7.08 0.27 Insomnia 6 8 0.75 2.15 0.26 0.79

Current smoker 8 7 1.14 0.41 3.15 1 .o

Hypnotic user 7 6 1.17 0.35 3.90 1 .o * McNemar’s test.

(22.4%: x2 = 26.42, df = 2, p < 0.001). Of those who survived, 10 were rescreened, and of these six were rated as ‘impaired’ and four as ‘unimpaired’, a rate of impairment significantly greater than that found among the surviving ‘unimpaired’ (x2 = 141.8, df = 4, p < 0.001).

Overall, 50 ‘at-risk’ respondents scored 1 9 on the CAPE I/O scale and 37 of these were clinically assessed. Clinical assessment found evidence of dementia, consistent with DSM-III-R criteria, in 30 cases. Of the 13 unavailable for clinical assess- ment, eight had died and one had moved out of the area between the screening and assessment phases of the study. A further four extant cases were unavailable for clinical interview, and were therefore classified on the basis of hospital records. Information from hospital case notes (where avail- able) confirmed a diagnosis of dementia in three of the 13 respondents eligible for assessment but not clinically assessed.

For those respondents who had died before the 1989 survey, a diagnosis of dementia was recorded in hospital notes in one case and on NHS death certificates in eight cases: In total, therefore, 42 cases of dementia were identified within the popula- tion at risk.

Risk estimates associated with each of the factors analysed are shown in Table 3. While some of these factors were associated with at least a doubling of risk (heart trouble, having ever smoked and falls), most showed excessive confidence limits, none achieved the criterion level of significance, and sta- tistical power was limited by sample size in all ana- lyses. Given the number of (1:l) matched pairs, and the proportion of controls exposed in the pres- ent study, odds ratios of 3.5 (for giddiness) and

5.0 (for the remaining factors) would have been necessary to achieve at least 80% power at the 5% (one-tailed) level of significance (see Breslow and Day, 1987). Such an increase in risk is almost cer- tainly unrealistic.

DISCUSSION

Given the representativeness of the original sample, the ability to match all cases with an appropriate control, the use of incident rather than prevalent cases and the known reliability of health and lifes- tyle data from the Nottingham Longitudinal Study, we feel that the present analyses offer a useful assessment of factors possibly associated with the onset of dementing illness. While the statistical power of these case-control comparisons was clearly limited by sample size, these data do provide insights into associations with, and the likely distri- bution of putative risk factors within a subsample of incident cases originating within a random sam- ple of elderly people living at home. Three factors (heart trouble, falls and having ever smoked) showed at least a doubling of risk. Cross-sectional studies have shown significant associations between current smoking and a reduced risk of cog- nitive impairment (Ebrahim et al., 1988; Grossberg et al., 1989), but these findings are not supported by the present longitudinal analyses. It is not unlik- ely, however, that in age-uncontrolled compari- sons, such as those reported by Ebrahim et al. (1988), negative cross-sectional associations between dementia and smoking may be explained by the selective survival of non-smokers. Certainly, recent prospective data from the United States

RISK FACTORS FOR DEMENTIA 15

(Herbert et al., 1992) show no increased risk of Alzheimer’s disease among current smokers. Nevertheless, the (non-significant) doubling of risk associated with having ever smoked is consistent with the suggestion that while smoking may not be a risk factor of Alzheimer’s disease, it may be a risk factor for vascular dementia. The heteroge- neity (as regards vascular and non-vascular dementias) of cases identified here prevented separ- ate analyses, and represents a further limitation of the present study. The remaining factors with odds ratios 1 2 also appear to merit further investigation using larger samples.

The validity of information recorded on death certificates also has implications for the present findings. However, while recent attention has focused on whether dementias are recorded on death certificates, the extent to which such record- ings are clinically valid remains unknown. Examin- ing the recorded causes of death among 84 known dementia sufferers, Burns et al. (1990) found that in 70% of cases the dementia syndrome was appro- priately recorded on the death certificate. In the present study, 48% of those respondents for whom there was evidence of dementia in 1985, and who had subsequently died, had this information recorded on their death certificates. It is possible, however, that the recognition of dementia as a cause, or contributory cause of death may be related to the severity-and hence clinical promi- nence-of the syndrome. If this is the case, then death certificate diagnoses of dementia may repre- sent valid, though under-representative infor- mation.

ACKNOWLEDGEMENTS

The Nottingham Longitudinal Study of Activity and Ageing is supported by the Grand Charity, Help the Aged and PPP Medical Trust. We are pleased to acknowledge the support of Professor Tom Arie and Drs E. Jane Byrne, Rob Jones and Jonathan Waite in clinically validating the survey ratings.

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