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Department of Psychiatry and Depression Clinical Research Centre, Chonnam National University Medical School, Kwangju
King's College London (Institute of Psychiatry), London, UK
Department of Psychiatry and Depression Clinical Research Centre, Chonnam National University Medical School, Kwangju, Korea
Correspondence: Professor Jin-Sang Yoon, Department of Psychiatry, Chonnam National University Medical School, 5 Hak-Dong, Dong-gu, Kwangju 501-757, Republic of Korea. Tel. +82 62 220 6142; fax: +82 62 225 2351; email: jsyoon{at}chonnam.ac.kr
Funding detailed in Acknowledgements.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Aims To investigate prospective associations between risk factors for vascular disease and incidence of late-life depression.
Method Of 661 community participants aged 65 years or over, without depression at baseline, 521 (79%) were re-evaluated 2 years later. At baseline and follow-up, a diagnostic interview for depression was carried out and information on vascular status, disability and cognitive function was gathered.
Results Pre-existing heart disease, incident stroke and lower baseline high-density lipoprotein cholesterol level were significantly associated with incidence of late-life depression, independently of disability and cognitive function.
Conclusions These results provide some support for a vascular aetiology of late-life depression. However, important risk factors for cerebrovascular disease such as hypertension and diabetes were not implicated, and the associations with lipid levels might still be explained by affective states earlier in life.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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METHOD |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Baseline sample and measurements
A cross-sectional survey of a geographically defined population was carried
out in 2001. The sampling procedure and measurements have been described
previously (Kim et al,
2003a,
2004). In brief, 732 community
residents aged 65 years or over, on national residents registration lists
within two areas of Kwangju, South Korea, were interviewed. Interviews
included a fully structured diagnostic interview for depression, examinations
for vascular disease risk and formal assessment of disability and cognitive
function.
Depression
Depression was assessed using the community version of the Geriatric Mental
State (GMS) diagnostic schedule (GMS B3;
Copeland et al, 1986).
This is a fully structured diagnostic instrument, in wide international use,
with an accompanying computerised algorithm. The GMS B3 was translated into
Korean according to a formal standardisation process
(Kim et al,
2003b). As in other studies, a stage-one
(non-hierarchical) confidence level of 3 or above in the Automated Geriatric
Examination for Computer Assisted Taxonomy (AGECAT) algorithm
(Copeland et al, 1986)
was used to define depression of clinical significance.
Vascular disease risk
Self-reported diagnoses of and treatment histories for stroke, heart
disease, hypertension and diabetes were recorded. Stroke was classified only
if there was a clear history of sudden onset of unilateral paralysis and/or
loss of speech and/or blindness lasting for at least 2 days. Heart disease was
classified on the basis of a previous medical diagnosis with a clear time of
onset. Resting blood pressure was taken with an automatic sphygmomanometer on
the left arm in the sitting position. The lower of two consecutive readings
was used. Blood samples were taken in a fasting state and were carried out in
the mornings where possible. The following assays were performed: glucose,
total cholesterol, HDL, low-density lipoprotein (LDL) and triglycerides.
Other potential risk factors for depression
Demographic data on age, gender and education were recorded. Disability was
assessed by the Korean version of the World Health Organization Disability
Assessment Schedule II (WHODAS II; Kim
et al, 2005). Cognitive function was evaluated by the
Korean version of the Mini-Mental State Examination (MMSE;
Park & Kwon, 1990).
Follow-up evaluation
Follow-up evaluation was carried out in 2003. The mean (s.d.) follow-up
period was 2.4 (0.3) years. Diagnosis of depression (GMS-AGECAT) and
information on new-onset vascular disease and risk (stroke, heart disease,
hypertension and diabetes) during the 2-year interval were ascertained. The
vascular examination, WHODAS II schedule and blood assays described above were
also repeated. Responses to certain individual GMS questions at follow-up were
also extracted for exploratory secondary analyses. These consisted of four
psychological depressive symptoms (depressed mood, tearfulness, guilt and
pessimism) and three vegetative symptoms (poor appetite, weight loss and sleep
disturbance).
Statistical analysis
For the analysis reported here, participants with depression at baseline
were excluded, and depression at follow-up was treated as the dependent
variable for primary analyses. Baseline characteristics of participants and
non-participants at follow-up were compared. Initial unadjusted analyses were
carried out to investigate vascular factors associated with incident
depression. For categorical independent variables, presence at baseline and
onset during the follow-up period were considered separately. For continuous
independent variables, baseline levels and changes in levels over the
follow-up period were considered separately. Incident depression was compared
across quintiles of baseline/change scores. Where curvilinear relationships
were suggested, associations were tested entering both linear and quadratic
terms for independent variable quintiles. Associations between independent and
dependent variables were further analysed using stepwise logistic regression
models to investigate confounding by demographic characteristics, and
mediation by change in level of disability (WHODAS II) from base-line to
follow-up.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Descriptive data
Of the 521 participants, 63 (12%) incident cases of depression were
identified. Preexisting stroke, heart disease, hypertension and diabetes had
been identified in 21 (4%), 99 (19%), 141 (27%) and 47 (9%) participants,
respectively. New-onset cases of stroke, heart disease, hypertension and
diabetes were found in 20 (4%), 31 (6%), 57 (11%) and 26 (5%) participants,
respectively. Mean (s.d.) baseline vascular examination measurements were as
follows: systolic blood pressure 146 (25) mmHg; diastolic blood pressure 88
(23) mmHg; blood glucose 106 (54) mg/dl; total cholesterol 175 (35) mg/dl; HDL
cholesterol 49 (15) mg/dl; LDL cholesterol 95 (32) mg/dl; triglycerides 156
(89) mg/dl. Mean (s.d.) changes in levels from baseline to follow-up were as
follows: systolic blood pressure +2 (28) mmHg; diastolic blood pressure -3
(24) mmHg; blood glucose +2 (54) mg/dl; total cholesterol +6 (32) mg/dl; HDL
cholesterol -1 (13) mg/dl; LDL cholesterol +14 (36) mg/dl; triglycerides +15
(91) mg/dl; and WHODAS II score +1 (12) units.
Associations between vascular disorders and incident depression
Unadjusted associations between vascular disorders and incident depression
are summarised in Table 2.
Incident depression was significantly associated with heart disease at
baseline and with stroke occurring during the follow-up period. Associations
with baseline or incident hypertension or diabetes were all positive, but were
weak and not statistically significant.
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Associations between incident depression and lipid levels are summarised in Table 3. For baseline total cholesterol, a significant U-shaped association with incident depression was observed, with highest risk in those with lower or higher baseline levels. This pattern was similar but not significant for LDL cholesterol. For HDL cholesterol, a strong and significant linear association was found between decreasing levels and increased incidence of depression. For changes in lipid levels over the follow-up period, U-shaped associations were suggested for total and LDL cholesterol, with highest risk in participants with declining or increasing levels. However, associations fell just short of statistical significance. No associations were found between incident depression and baseline blood pressure or blood glucose, nor with changes in these factors over the follow-up period (data not shown).
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Multivariate analysis
Results of logistic regression analyses are summarised in
Table 4. In general, odds
ratios were not changed substantially following each adjustment. In the fully
adjusted model, independent associations were found with baseline heart
disease and lower level of HDL cholesterol, and the association with incident
stroke bordered on statistical significance. The quadratic term for the
relationship between quintiles of baseline total cholesterol and incident
depression also remained significant after adjustment for all factors listed
in Table 4 (unadjusted odds
ratio=1.32, P=0.009; adjusted odds ratio=1.29, P=0.015).
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Secondary analyses
Of the 521 followed-up participants who were not depressed at the baseline,
7 (1%) were taking antidepressants. No marked or consistent differences were
found in the results when the above analyses were repeated excluding this
group. Results were also not changed if baseline WHODAS II score was entered,
rather than change from baseline to follow-up.
The prevalence at follow-up of four psychological depressive symptoms were: depressed mood 42%, tearfulness 31%, guilt 14%, and pessimism 23%; and of three vegetative symptoms were: poor appetite 33%, weight loss 27% and sleep disturbance 42%. In a secondary analysis, pre-existing heart disease was significantly associated with depressed mood, tearfulness and guilt (P<0.05) and was associated with pessimism at borderline levels of statistical significance (P=0.060). Incident stroke was significantly associated with all four of these symptoms (P<0.05). No significant associations were found between either of these factors and the three vegetative symptoms (P>0.20). Lower baseline HDL cholesterol levels, on the other hand, were significantly associated with all seven symptoms (P<0.05). The quadratic term for total cholesterol was significantly associated with all but five outcomes (P<0.05) and was associated with the remaining two at borderline levels of significance (for guilt P=0.064; for pessimism P=0.071).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Methodological issues
Most previous community studies investigating the association between
vascular risk factors and depression in older people have been cross-sectional
in design (Stewart et al,
2001; Kim et al,
2004). This limits the extent to which causal relationships can be
clarified, particularly for factors such as blood pressure and lipid levels,
which may well be altered in depressed states. Previous prospective studies
have been limited in number and also in the use of brief screening instruments
to define depression (Lyness et
al, 2000), or by the specific nature of the cohorts analysed
(Cervilla et al,
2004). Strengths of our study were that prospective data on both
depression and potential risk factors were obtained from a community
population, and that depression was ascertained using a widely validated
diagnostic instrument. The follow-up rate was reasonable and not apparently
differential with respect to risk factors of interest. A limitation of the
study was that information on some vascular factors such as stroke and heart
disease relied on self-reported diagnoses and corroboration by medical records
was not possible. Neuroimaging was also not feasible in this population.
Furthermore, it should be borne in mind that most participants will have had
moderate levels of depression, and the results may not be generalisable to
secondary care clinical samples with more severe syndromes.
Heart disease, stroke and depression
Reported heart disease was significantly associated with incidence of
late-life depression in the present study, consistent with other research
(Hippisley-Cox et al,
1998). Depression following myocardial infarction has been
associated with higher mortality, and it is likely that the true association
between cardiovascular disease and depression is underestimated because of
differential mortality. Associations between previous stroke and depression
are also well recognised in community samples
(Fuh et al, 1997;
Stewart et al, 2001;
Kim et al, 2004). In
our study the association was stronger for stroke occurring during the
follow-up period than for that reported at baseline. This is likely to reflect
a reduction in risk with increased duration since exposure, but might also be
accounted for by differential attrition. As with previous cross-sectional
studies, we found that this association was not entirely explained by level of
disability (Stewart et al,
2001; Kim et al,
2004) which, as for heart disease, may reflect either specific
biological causal pathways or unmeasured psychological factors (such as the
impact of the diagnosis). In this respect, it is noteworthy that the
association (in contrast to that of lipid levels) appeared to be principally
explained by cognitive rather than vegetative symptoms, which supports the
latter causal pathway over the former.
Total cholesterol levels and depression
Previous studies investigating the association between total cholesterol
levels and depression in later life have reported conflicting findings. Some
have found significant associations with low cholesterol levels
(Morgan et al, 1993),
while others have found no associations
(Blazer et al, 2002;
Kim et al, 2004). In
this prospective study we found that risk of depression at follow-up was
associated with both high and low total cholesterol levels at baseline.
Incident depression also appeared to be associated with both rising and
falling total cholesterol levels over the follow-up period, although these
associations fell below conventional levels of statistical significance. These
findings are likely to represent mixed processes. High cholesterol, as a risk
factor for arterial disease, may also be a risk factor for depression. Low
cholesterol, on the other hand, is associated with frailty and poor health
(Corti et al, 1997),
which in turn are important risk factors for depression. Hypocholesterolaemia
might also have direct risk effects, for example through reduced serotonin
levels (Engelberg, 1992).
Unfortunately data were not collected on cholesterol-lowering agents. However,
we believe that the use of these agents is rare in this population and is
unlikely to explain our observed associations.
Vascular risk factors and depression
In a previous cross-sectional analysis of the baseline population for this
study, we had found that low HDL cholesterol levels were associated with
depression (Kim et al,
2004). In this prospective analysis, low HDL cholesterol also
predicted incident depression. Furthermore, there were no apparent changes in
HDL cholesterol levels in participants who became depressed, reducing the
likelihood of reverse causality as an explanation. White matter abnormalities
on neuroimaging are found more frequently than expected in people with
late-life depression (de Groot et
al, 2000), supporting vascular aetiology in at least some
cases. However, population-based studies have frequently failed to find
associations between depression and conventional vascular risk factors such as
hypertension and diabetes (Jones-Webb
et al, 1996; Rajala
et al, 1997; Stewart
et al, 2001). Where associations have been found, it is
unclear whether these are specific to the disorders themselves or explained by
well-recognised associations between depression and worse physical health. The
association with an atherogenic lipid profile is consistent with a vascular
basis for late-life depression, but the weak or absent associations with
reported hypertension or diabetes (or with recorded blood pressure or blood
glucose) are not supportive. A neuropathological study also found that
late-life depression was associated with arterial atheroma rather than
microvascular disease (Thomas et
al, 2001), and it is possible that vascular mechanisms
underlying late-life depression have a different pattern to those implicated
in stroke and vascular dementia. However, it is also possible that
associations are explained by earlier unrecalled affective states which
increase risk for both cardiovascular pathology and late-life depression.
Vascular disease, vascular risk factors and depression are common conditions
in older populations, and are associated with high levels of morbidity. Our
findings provide some epidemiological support for vascular factors in the
aetiology of late-life depression
(Alexopoulos et al,
1997). However, prospective data over a longer follow-up period
(possibly from early adulthood) are likely to be required before firm
conclusions can be drawn concerning the direction of association between these
two processes.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Blazer, D. G., Burchett, B. B. & Fillenbaum, G. G.
(2002) APOE e4 and low cholesterol as risks for depression in
a biracial elderly community sample. American Journal of Geriatric
Psychiatry, 10, 515
-520.
Cervilla, J., Prince, M. & Rabe-Hesketh, S. (2004) Vascular disease risk factors as determinants of incident depressive symptoms: a prospective community-based study. Psychological Medicine, 34, 635 -641.[CrossRef][Medline]
Copeland, J. R. M., Dewey, M. E. & Griffiths-Jones, H. M. (1986) A computerized psychiatric diagnostic system and case nomenclature for elderly subjects: GMS and AGECAT. Psychological Medicine, 16, 89 -99.[Medline]
Corti, M.-C., Guralnik, J. M., Salive, M. E., et al
(1997) Clarifying the direct relation between total
cholesterol levels and death from coronary heart disease in older persons.
Annals of Internal Medicine,
126, 753
-760.
de Groot, J. C., de Leeuw, F. E., Oudkerk, M., et al
(2000) Cerebral white matter lesions and depressive symptoms
in elderly adults. Archives of General Psychiatry,
57, 1071
-1076.
Engelberg, H. (1992) Low serum cholesterol and suicide. Lancet, 339, 727 -729.[CrossRef][Medline]
Fuh, J. L., Liu, H. C.,Wang, S. J., et al
(1997) Poststroke depression among the Chinese elderly in a
rural community. Stroke,
28, 1126
-1129.
Hippisley-Cox, J., Fielding, K., Pringle, M.
(1998) Depression as a risk factor for ischaemic heart
disease in men: population based case-control study.
BMJ, 316, 1714
-1719.
Jones-Webb, R., Jacobs Jr., D. R., Flack, J. M., et al (1996) Relationships between depressive symptoms, anxiety, alcohol consumption, and blood pressure: results from the CARDIA Study. Alcoholism: Clinical and Experimental Research, 20, 420 -427.[CrossRef][Medline]
Kim, J.-M., Stewart, R., Shin, I.-S., et al
(2003a) Limb length and dementia in an older Korean
population. Journal of Neurology, Neurosurgery and
Psychiatry, 74, 427
-432.
Kim, J.-M., Stewart, R., Prince, M., et al (2003b) Diagnosing dementia in a developing nation: an evaluation of the GMS-AGECATalgorithm in an older Korean population. International Journal of Geriatric Psychiatry, 18, 331 -336.[CrossRef][Medline]
Kim, J.-M., Stewart, R., Shin, I.-S., et al
(2004) Vascular disease/risk and late-life depression in a
Korean community population. British Journal of
Psychiatry, 185, 102
-107.
Kim, J.-M., Stewart, R., Glozier, N., et al (2005) Physical health, depression and cognitive function as correlates of disability in an older Korean population. International Journal of Geriatric Psychiatry, 20, 160 -167.[CrossRef][Medline]
Larson, S. L., Owens, P. L., Ford, D., et al
(2001) Depressive disorder, dysthymia, and risk of stroke.
Thirteen-year follow-up from the Baltimore Epidemiologic Catchment Area Study.
Stroke, 32, 1979
-1983.
Lyness, J. M., King, D. A., Conwell,Y., et al
(2000) Cerebrovascular risk factors and 1-year depression
outcome in older primary care patients. American Journal of
Psychiatry, 157, 1499
-1501.
Morgan, R. E., Palinkas, L. A., Barrett-Connor, E. L., et al (1993) Plasma cholesterol and depressive symptoms in older men. Lancet, 341, 75 -79.[CrossRef][Medline]
Park, J. H. & Kwon,Y. C. (1990) Modification of the mini-mental state examination for use in the elderly in a non-western society: Part I. Development of Korean version of Mini-Mental State Examination. International Journal of Geriatric Psychiatry, 5, 381 -387.[CrossRef]
Prince, M., Acosta, D., Chiu, H., et al (2003) Dementia diagnosis in developing countries: a cross-cultural validation study. Lancet, 361, 909 -917.[CrossRef][Medline]
Rajala, U., Keinanen-Kiukaanniemi, S. & Kevela, S. L. (1997) Non-insulin-dependent diabetes mellitus and depression in a middle-aged Finnish population. Social Psychiatry and Psychiatric Epidemiology, 32, 363 -367.[CrossRef][Medline]
Stewart, R., Prince, R., Prince, M., Mann, M., Mann, A., et
al (2001) Stroke, vascular risk factors and depression.
Cross-sectional study in a UK Caribbean-born population. British
Journal of Psychiatry, 178, 23
-28.
Thomas, A. J., Ferrier, I. N., Kalaria Kalaria,, R. N., et
al (2001) A neuropathological study of vascular factors
in late-life depression. Journal of Neurology, Neurosurgery and
Psychiatry, 70, 83
-87.
Received for publication July 7, 2005. Revision received November 21, 2005. Accepted for publication December 19, 2005.
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