© 2006 The Royal College of Psychiatrists
Natural history of depression in the oldest old
Population-based prospective study
Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Centre, Leiden, and Department of Psychiatry, Valeriuskliniek GGZ Buitenamstel, Vrije Universiteit, Amsterdam
Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Centre, Leiden
Department of Psychiatry, Leiden University Medical Centre, Leiden
Department of Psychiatry, Valeriuskliniek GGZ Buitenamstel, Vrije Universiteit, Amsterdam
Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands
Correspondence: Dr Max L. Stek, Leiden University Medical Centre, Section of Gerontology and Geriatrics, C2-R, PO Box 9600, 2300 RC Leiden, The Netherlands. Tel: +31 715266640; fax: +31 715248159; e-mail: m.l.stek{at}ggzba.nl
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Background Despite its negative consequences, little is known about the natural history of depression in the oldest old.
Aims To study the incidence, course and predictors of depression in the general population of the oldest old.
Method The Leiden 85-plus Study is a prospective population-based study of 500 people from their 85th to their 89th birthdays. Depressive symptoms were annually assessed with the 15-item Geriatric Depression Scale, using a cut-off of 4 points.
Results During a mean follow-up of 3.9 years, the annual risk for the emergence of depression was 6.8%. Poor daily functioning and institutionalisation predicted depression. Among the 77 participants with depression at baseline (prevalence 15%) the annual remission rate was ony 14%. In more than half of the participants with a remission of depression, we observed a relapse of depression during follow-up. No predictors of remission could be identified.
Conclusions Among the oldest old, depression is frequent and highly persistent. More active case-finding and treatment would be potentially rewarding.
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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Depression ranks among the most significant health problems in older adults but is potentially treatable at all ages. The consequences of both major and minor depression in older adults are severe and include diminished quality of life, functional decline, marked disability, increased service utilisation and high mortality from comorbid medical conditions. To date, few studies have been published on the incidence of depression in the oldest old and none about its course (Meller et al, 1996; Haynie et al, 2001; Palsson et al, 2001). Given the rapidly increasing number of older adults in society, we studied the incidence and course of depression in the oldest old within the Leiden 85-plus Study.
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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Study design
The Leiden 85-plus Study is a population-based prospective study of a large cohort of community-dwelling older adults in Leiden, The Netherlands. Between 1997 and 1999 all members of the 1912-1914 birth cohort living in Leiden were enrolled in the month of their 85th birthday. No a priori selection criteria with respect to health, cognitive functioning or living situation were applied.
Study setting and procedures
The community of Leiden, consisting of 120 000 inhabitants, is a mostly
urban area in the western part of The Netherlands with a mixed socio-economic
make-up. Demographic characteristics of the participants were representative
of the general Dutch population of 85-year-old persons. Upon enrolment,
information was given by mail; further contact was made by telephone or a home
visit to ask for approval. Participants were then visited at their place of
residence by medical staff and research nurses. During the baseline visits,
structured face-to-face interviews were conducted, an electrocardiogram was
recorded and blood samples were collected. Follow-up interviews were carried
out for all eligible participants each year during the study period of 4
years. The medical ethics committee of the Leiden University Medical Centre
approved the study.
Depression
Each year we administered the 15-item Geriatric Depression Scale (GDS-15),
a questionnaire especially developed as a screening instrument for the
presence of depressive symptoms in elderly populations
(Sheik & Yesavage, 1986).
Depression was considered present when the score on the GDS-15 was 5 points or
more. This cut-off gives the best sensitivity and specificity for the presence
of major depression in the general population
(Sheik & Yesavage, 1986),
in geriatric in-patients (Shah et
al, 1996), in primary care settings
(D'Ath et al, 1994;
Lyness et al, 1997)
and in medical in-patients (Pomeroy et
al, 2001), and was found to have a good specificity (0.85) in
a representative sample of community-dwelling oldest old for the presence of
major depression (de Craen et al,
2003). Because the reliability and the validity of the GDS-15 are
compromised in older adults with serious cognitive impairment, the GDS-15 was
not administered to participants with a Mini-Mental State Examination (MMSE;
Folstein et al, 1975)
score of less than 19 points.
Incidence and course
The incidence of depression was studied by following the participants
without depression at baseline, defined as having a GDS-15 score of 0-2 points
at age 85 years, over a 4-year period. Incident depression was considered to
be present when the GDS-15 increased to 5 points or more during the follow-up
measurements.
The course of depression was studied by following the participants with depression at baseline, defined as a GDS-15 score of 5 points or more, for 4 years. Remission of depression was defined as returning to a GDS-15 score of 0-2 points at any measurement during follow-up.
Risk factors
Demographic variables
Gender, marital status, living arrangements, loss of a spouse, income and
institutionalisation were recorded. The majority of participants had received
only compulsory primary school education; a minority had additional education.
Therefore the level of education was dichotomised at 6 years. As low income is
a putative risk factor (Cole &
Dendukuri, 2003) the income was dichotomised across state pension
only and state pension plus additional income.
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Fig. 1 (a) The cumulative incidence of depression in 334 participants without
depression at baseline, defined as a score on the 15-item Geriatric Depression
Scale (GDS-15) between 0 and 2 points, from age 85 to 89 years. Incident
depression was defined as a GDS-15 score  5 points during any of the
follow-up measurements.(b) The cumulative persistence of depression in 77 participants with depression at baseline, from 85 to 89 years. Remission was defined as a GDS-15 score of 0-2 points at any of the follow-up measurements.
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The Groningen Activity Restriction Scale (GARS; Kempen et al, 1996) was applied to measure disability in daily functioning. Poor daily functioning was defined as a GARS score above 23 points (33rd percentile). Furthermore, the self-rated presence of loneliness was assessed.
Health-related correlates
Information on the use of medication was obtained from the pharmacists'
registers. Data on physical diseases were obtained via a structured
questionnaire and based on general practitioners' diagnoses, blood samples and
the results of the electrocardiogram. These included cardiovascular disease
(stroke, myocardial infarction or ischaemia, arterial surgery, intermittent
claudication), malignancy, Parkinson's disease, diabetes mellitus, chronic
obstructive pulmonary disease, and arthritic disease at baseline or in the
past. Diabetes was considered present in the case of a positive medical
history, or current use of antidiabetic medication, or a non-fasting glucose
concentration of 11.1 mmol/l or higher.
Statistical analysis
First, to make optimal use of the repetitive measurements and to correct
for attrition due to mortality and cognitive decline, the cumulative incidence
and the cumulative remission rate of depression with the corresponding 95% CI
were calculated from life tables. The assumption was made that depression
developed or remitted midway during the follow-up period in which the
participant passed the GDS-15 cut-off point. Second, relative risks (and 95%
CI) of risk factors for the incidence and the remission of depression were
calculated in a Cox proportional hazards model, with the assumption that
depression developed or remitted midway during the follow-up period in which
the participant passed the GDS-15 cut-off point.
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Baseline assessments
During the study period 705 inhabitants of Leiden reached 85 years of age and were eligible to participate. Fourteen died before they could be enrolled and 92 refused to participate. At baseline the response rate was 87%, resulting in a sample of 599 participants. There were no significant differences for various socio-demographic characteristics and the presence of depressive symptoms between the 599 participants and the source population (Bootsma-van der Wiel et al, 2002). Of the 599, 500 had MMSE scores of 19 points or more and were included in the present analysis. Of the 500 participants at baseline, 334 (67%) had no significant symptoms of depression, as evidenced by GDS scores of 0-2 points.
Incidence of depression
During follow-up, the mean total GDS-15 score increased significantly from
0.96 (s.d.=0.80) points at baseline to 2.3 (s.d.=2.7) at age 89 years (paired
t-test, P<0.001).
Table 1 shows the incidence of
depression, defined as a GDS-15 score of 5 points or more, in the 334
participants without depression at baseline. During a follow-up of 827
person-years at risk, depression occurred in 56 participants (incidence rate
68 per 1000 person-years, 95% CI 50-85), amounting to an annual risk of 6.8%.
Figure 1 illustrates the
cumulative incidence of depression from age 85 to age 89 years.
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Table 1 The incidence of
depression1
during a 4-year follow-up of 334 participants without depression at
baseline2 from
age 85 years
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Risk factors for the incidence of depression
Table 2 shows the impact of
various risk factors for the emergence of depression. Neither demographic
characteristics nor any of the health-related characteristics contributed to
the incidence of depression. Institutionalisation and poor daily functioning
were associated with an increased risk of the development of depresssion. The
GDS-15 score at baseline was associated with an almost twofold increased risk
per point increase. After adjustment for the GDS-15 score at baseline, the
increased risks of depression due to institutionalisation (relative risk=2.8,
95% CI 1.3-6.4) and poor daily functioning (relative risk=1.9, 95% CI 1.1-3.4)
were sustained.
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Table 2 The risk of depression during follow-up in 334 participants without
depression at baseline in relation to socio-demographic characteristics, daily
functioning and health characteristics
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Remission of depression
Of the 500 participants at baseline, 77 had GDS scores of 5 points or more,
indicating depression (prevalence 15%, 95% CI 12-18%). During the 4-year
follow-up we observed a remission in 16 participants, with an annual remission
probability of 14% (Fig. 1b).
Remission was sustained in 7 of the 16 participants, whereas in 9 participants
there was a relapse during follow-up. None of the factors described in
Table 2 significantly predicted
remission (data not shown).
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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In the present study, we have annually assessed the presence of depression in a large representative sample of community-dwelling oldest old persons. We show that the oldest old are at high risk of developing depression and that, when present, depression is highly persistent. Predictors of depression in the oldest old were institutionalisation and poor daily functioning, but no predictors were identified for remission.
Other studies
In one of the few longitudinal studies of depression in the old-old (79-85
years), Palsson et al
(2001) reported an incidence
of depression according to DSM-III-R criteria
(American Psychiatric Association,
1987) of 44 per 1000 person-years, associated with female gender.
The lower incidence compared with our estimate of 70 per 1000 person-years is
possibly due to the younger age of their participants. An age-associated
increase in the incidence of depression is further strengthened by the
findings of Meller et al
(1996), who described a very
high incidence of 140 per 1000 person-years in a population of octo- and
nonagenarians (85-103 years). Changes in living situation and dementia were
the main risk factors in their study, but these did not reach statistical
significance. As changes in living situation in this age-group usually mean
moving to institutionalised living, this seems to be in line with the finding
of institutionalisation as a predictor of depression. The lower incidence of
depression reported by Haynie et al
(2001) from the OCTO-Twin study
may be explained by their selection of very healthy persons at entry.
Course of depression in the oldest old
In contrast to previous studies on the incidence of depression, no data
were available on its course in the oldest old. A strong tendency for chronic
depression has been reported in the younger elderly
(Beekman et al, 2002).
Persistence of depression in the younger elderly could be extrapolated to the
oldest old.
Possible limitations
An important limitation of our study is that depression was not formally
diagnosed. The GDS-15 was originally developed as a screening instrument for
depressive illness in older adults, not as a diagnostic procedure. However,
given the nature and size of this study, further diagnostic procedures were
not feasible. This lack of a second-stage standardised assessment of
depression may have resulted in higher incidence and lower remission figures
in our study. However, the GDS-15 was found to have a good specificity (0.85)
in a representative sample of community-dwelling oldest old for the presence
of major depression (de Craen et
al, 2003). Moreover, it is becoming increasingly clear that
significant depressive symptoms in older adults have as distinct deleterious
effects as formally diagnosed depressive disorders
(Gallo et al, 1997).
It could also be questioned whether the GDS-15 is able to detect changes in
depressive symptoms over time. Within the Leiden 85-plus Study, we
demonstrated that the loss of a partner, which is a major negative life event
and an important risk factor for the emergence of depression in older adults,
was associated with a significant increase of more than two points on the
GDS-15 (Vinkers et al,
2004a). Thus, the chosen GDS-15 criteria for the
incidence and remission of depression should enable us to measure a relatively
robust change in depressive symptoms over time.
Although the initial response rate in this study was very high, substantial attrition owing to mortality and cognitive decline is an intrinsic part of all prospective studies of depression in the oldest old. In an earlier analysis, we found an almost twofold increased mortality risk for oldest old participants of the Leiden 85-plus Study with depression; this was sustained when corrected for demographic and health-related factors (Stek et al, 2005). In the present study, refusal to participate was not related to depression at baseline (Bootsma-van der Wiel et al, 2002), but participants with incident depression might have refused more often at follow-up. Confounding by effects of specific treatment is probably very limited because, as reported before, the use of antidepressants was almost non-existent at baseline (Stek et al, 2004). We did not identify determinants that predicted remission, but as depression is associated with refusal and mortality, the numbers in our study might have been too small to detect these effects.
Role of cognitive functioning and early dementia
Depression and early dementia are closely linked. Earlier we showed that
cognitive impairment at baseline predicted an accelerated increase of
depressive symptoms in the oldest old, whereas depression at baseline was not
related to increased cognitive decline
(Vinkers et al,
2004b). Thus, cognitive impairment preceded depression
but depression did not herald cognitive decline. Cognitive impairment or
early-stage dementia might well play an important role in the high incidence
of depression and its persistence in the oldest old, but the underlying
mechanisms are still unresolved. Since participants who developed serious
cognitive impairment (MMSE <19 points) were excluded from our study,
incidence rates for depression may even have been underestimated.
Treatment of depression in the oldest old
Notwithstanding a lack of knowledge about the origins of depression in the
oldest old, from a clinical perspective it is very important that depression
occurs often in this age-group and has a poor prognosis. Poor daily
functioning and institutionalisation are strong predictors of incident
depression in the oldest old. In an earlier study of the oldest old
(Stek et al, 2004),
the recognition of depression by the general practitioner was poor and
antidepressive treatment virtually non-existent. Taken together with the
results of the present study, it is clear that more active case-finding is
warranted, as treatment of depression in the oldest old is as potentially
rewarding as in younger people.
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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CLINICAL IMPLICATIONS
- Depression occurs frequently and is highly persistent in the oldest
old.
- Poor daily functioning and institutionalisation at baseline predicted
depression.
- More active case-finding and treatment of depression in the oldest old
would be potentially rewarding.
LIMITATIONS
- Depression was not formally diagnosed.
- Participants with severe cognitive impairment (Mini-Mental State
Examination score of less than19) were excluded from the analyses.
- Substantial attrition due to mortality and cognitive decline is an
intrinsic part of all prospective studies of depression in the oldest old.
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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