10-year trajectories of depressive symptoms and risk of dementia: a population-based study

Late-life depressive symptoms have been extensively studied for their relationship with incident dementia, but have been typically assessed at a single timepoint. Such an approach neglects the course of depression, which, given its remitting and relapsing nature, might provide further insights into...

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Published in:The Lancet. Psychiatry Vol. 3; no. 7; pp. 628 - 635
Main Authors: Mirza, Saira Saeed, Wolters, Frank J, Swanson, Sonja A, Koudstaal, Peter J, Hofman, Albert, Tiemeier, Henning, Ikram, M Arfan
Format: Journal Article
Language:English
Published: England 01.07.2016
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ISSN:2215-0374
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Abstract Late-life depressive symptoms have been extensively studied for their relationship with incident dementia, but have been typically assessed at a single timepoint. Such an approach neglects the course of depression, which, given its remitting and relapsing nature, might provide further insights into the complex association of depression with dementia. We therefore repeatedly measured depressive symptoms in a population of adults over a decade to study the subsequent risk of dementia. Our study was embedded in the Rotterdam Study, a population-based study of adults aged 55 years or older in Rotterdam (Netherlands), ongoing since 1990. The cohort is monitored continuously for major events by data linkage between the study database and general practitioners. We examined a cohort of participants who were free from dementia, but had data for depressive symptoms from at least one examination round in 1993-95, 1997-99, or 2002-04. We assessed depressive symptoms with the validated Dutch version of the Center for Epidemiology Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale-Depression. We used these data to identify 11-year trajectories of depressive symptoms by latent class trajectory modelling. We screened participants for dementia at each examination round and followed up participants for 10 years for incident dementia by latent trajectory from the third examination round to 2014. We calculated hazard ratios (HR) for dementia by assigned trajectory using two Cox proportional hazards models (model 1 adjusted for age and sex only, and model 2 adjusted additionally for APOEɛ4 carrier status, educational level, body-mass index, smoking, alcohol consumption, cognitive score, use of antidepressants, and prevalent disease status at baseline). We repeated the analyses censoring for incident stroke, restricting to Alzheimer's disease as an outcome, and accounting for mortality as a competing risk for dementia. From 1993-2004, we obtained data for depressive symptoms from at least one examination round for 3325 participants (median age: 74·88 years [IQR 70·62-80·06], 1995 [60%] women). We identified five trajectories of depressive symptoms in these 3325 individuals, characterised by maintained low CES-D scores (low; 2441 [73%]); moderately high starting scores but then remitting (decreasing; 369 [11%]); low starting scores, increasing, then remitting (remitting; 170 [5%]); low starting scores that steadily increased (increasing; 255 [8%]); and maintained high scores (high; 90 [3%]). During 26 330 person-years, 434 participants developed incident dementia. Only the trajectory with increasing depressive symptoms was associated with a higher risk of dementia compared with the low depressive symptom trajectory, using model 2 (HR 1·42, 95% CI 1·05-1·94; p=0·024). Additionally, only the increasing trajectory was associated with a higher risk of dementia compared with the low trajectory after censoring for incident stroke (1·58, 1·15-2·16; p=0·0041), restricting to Alzheimer's disease as an outcome (1·44, 1·03-2·02; p=0·034), and accounting for mortality as a competing risk (1·45, 1·06-1·97; p=0·019). Risk of dementia differed with different courses of depression, which could not be captured by a single assessment of depressive symptoms. The higher risk of dementia only in the increasing trajectory suggests depression might be a prodrome of dementia. Erasmus Medical Center; ZonMw; the Netherlands Ministry of Education Culture and Science; and the Netherlands Ministry for Health, Welfare and Sports.
AbstractList Late-life depressive symptoms have been extensively studied for their relationship with incident dementia, but have been typically assessed at a single timepoint. Such an approach neglects the course of depression, which, given its remitting and relapsing nature, might provide further insights into the complex association of depression with dementia. We therefore repeatedly measured depressive symptoms in a population of adults over a decade to study the subsequent risk of dementia. Our study was embedded in the Rotterdam Study, a population-based study of adults aged 55 years or older in Rotterdam (Netherlands), ongoing since 1990. The cohort is monitored continuously for major events by data linkage between the study database and general practitioners. We examined a cohort of participants who were free from dementia, but had data for depressive symptoms from at least one examination round in 1993-95, 1997-99, or 2002-04. We assessed depressive symptoms with the validated Dutch version of the Center for Epidemiology Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale-Depression. We used these data to identify 11-year trajectories of depressive symptoms by latent class trajectory modelling. We screened participants for dementia at each examination round and followed up participants for 10 years for incident dementia by latent trajectory from the third examination round to 2014. We calculated hazard ratios (HR) for dementia by assigned trajectory using two Cox proportional hazards models (model 1 adjusted for age and sex only, and model 2 adjusted additionally for APOEɛ4 carrier status, educational level, body-mass index, smoking, alcohol consumption, cognitive score, use of antidepressants, and prevalent disease status at baseline). We repeated the analyses censoring for incident stroke, restricting to Alzheimer's disease as an outcome, and accounting for mortality as a competing risk for dementia. From 1993-2004, we obtained data for depressive symptoms from at least one examination round for 3325 participants (median age: 74·88 years [IQR 70·62-80·06], 1995 [60%] women). We identified five trajectories of depressive symptoms in these 3325 individuals, characterised by maintained low CES-D scores (low; 2441 [73%]); moderately high starting scores but then remitting (decreasing; 369 [11%]); low starting scores, increasing, then remitting (remitting; 170 [5%]); low starting scores that steadily increased (increasing; 255 [8%]); and maintained high scores (high; 90 [3%]). During 26 330 person-years, 434 participants developed incident dementia. Only the trajectory with increasing depressive symptoms was associated with a higher risk of dementia compared with the low depressive symptom trajectory, using model 2 (HR 1·42, 95% CI 1·05-1·94; p=0·024). Additionally, only the increasing trajectory was associated with a higher risk of dementia compared with the low trajectory after censoring for incident stroke (1·58, 1·15-2·16; p=0·0041), restricting to Alzheimer's disease as an outcome (1·44, 1·03-2·02; p=0·034), and accounting for mortality as a competing risk (1·45, 1·06-1·97; p=0·019). Risk of dementia differed with different courses of depression, which could not be captured by a single assessment of depressive symptoms. The higher risk of dementia only in the increasing trajectory suggests depression might be a prodrome of dementia. Erasmus Medical Center; ZonMw; the Netherlands Ministry of Education Culture and Science; and the Netherlands Ministry for Health, Welfare and Sports.
BACKGROUNDLate-life depressive symptoms have been extensively studied for their relationship with incident dementia, but have been typically assessed at a single timepoint. Such an approach neglects the course of depression, which, given its remitting and relapsing nature, might provide further insights into the complex association of depression with dementia. We therefore repeatedly measured depressive symptoms in a population of adults over a decade to study the subsequent risk of dementia.METHODSOur study was embedded in the Rotterdam Study, a population-based study of adults aged 55 years or older in Rotterdam (Netherlands), ongoing since 1990. The cohort is monitored continuously for major events by data linkage between the study database and general practitioners. We examined a cohort of participants who were free from dementia, but had data for depressive symptoms from at least one examination round in 1993-95, 1997-99, or 2002-04. We assessed depressive symptoms with the validated Dutch version of the Center for Epidemiology Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale-Depression. We used these data to identify 11-year trajectories of depressive symptoms by latent class trajectory modelling. We screened participants for dementia at each examination round and followed up participants for 10 years for incident dementia by latent trajectory from the third examination round to 2014. We calculated hazard ratios (HR) for dementia by assigned trajectory using two Cox proportional hazards models (model 1 adjusted for age and sex only, and model 2 adjusted additionally for APOEɛ4 carrier status, educational level, body-mass index, smoking, alcohol consumption, cognitive score, use of antidepressants, and prevalent disease status at baseline). We repeated the analyses censoring for incident stroke, restricting to Alzheimer's disease as an outcome, and accounting for mortality as a competing risk for dementia.FINDINGSFrom 1993-2004, we obtained data for depressive symptoms from at least one examination round for 3325 participants (median age: 74·88 years [IQR 70·62-80·06], 1995 [60%] women). We identified five trajectories of depressive symptoms in these 3325 individuals, characterised by maintained low CES-D scores (low; 2441 [73%]); moderately high starting scores but then remitting (decreasing; 369 [11%]); low starting scores, increasing, then remitting (remitting; 170 [5%]); low starting scores that steadily increased (increasing; 255 [8%]); and maintained high scores (high; 90 [3%]). During 26 330 person-years, 434 participants developed incident dementia. Only the trajectory with increasing depressive symptoms was associated with a higher risk of dementia compared with the low depressive symptom trajectory, using model 2 (HR 1·42, 95% CI 1·05-1·94; p=0·024). Additionally, only the increasing trajectory was associated with a higher risk of dementia compared with the low trajectory after censoring for incident stroke (1·58, 1·15-2·16; p=0·0041), restricting to Alzheimer's disease as an outcome (1·44, 1·03-2·02; p=0·034), and accounting for mortality as a competing risk (1·45, 1·06-1·97; p=0·019).INTERPRETATIONRisk of dementia differed with different courses of depression, which could not be captured by a single assessment of depressive symptoms. The higher risk of dementia only in the increasing trajectory suggests depression might be a prodrome of dementia.FUNDINGErasmus Medical Center; ZonMw; the Netherlands Ministry of Education Culture and Science; and the Netherlands Ministry for Health, Welfare and Sports.
Author Tiemeier, Henning
Mirza, Saira Saeed
Wolters, Frank J
Koudstaal, Peter J
Hofman, Albert
Ikram, M Arfan
Swanson, Sonja A
Author_xml – sequence: 1
  givenname: Saira Saeed
  surname: Mirza
  fullname: Mirza, Saira Saeed
  organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands
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  givenname: Frank J
  surname: Wolters
  fullname: Wolters, Frank J
  organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
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  givenname: Sonja A
  surname: Swanson
  fullname: Swanson, Sonja A
  organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands
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  surname: Koudstaal
  fullname: Koudstaal, Peter J
  organization: Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
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  givenname: Albert
  surname: Hofman
  fullname: Hofman, Albert
  organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands
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  fullname: Tiemeier, Henning
  organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Child and Adult Psychiatry, Erasmus Medical Center, Rotterdam, Netherlands; Department of Psychiatry, Erasmus Medical Center, Rotterdam, Netherlands
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  givenname: M Arfan
  surname: Ikram
  fullname: Ikram, M Arfan
  email: m.a.ikram@erasmusmc.nl
  organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, Netherlands. Electronic address: m.a.ikram@erasmusmc.nl
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27138970$$D View this record in MEDLINE/PubMed
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PublicationTitle The Lancet. Psychiatry
PublicationTitleAlternate Lancet Psychiatry
PublicationYear 2016
References 27138969 - Lancet Psychiatry. 2016 Jul;3(7):593-5
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Snippet Late-life depressive symptoms have been extensively studied for their relationship with incident dementia, but have been typically assessed at a single...
BACKGROUNDLate-life depressive symptoms have been extensively studied for their relationship with incident dementia, but have been typically assessed at a...
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SubjectTerms Aged
Aged, 80 and over
Cohort Studies
Dementia - epidemiology
Dementia - psychology
Depression - diagnosis
Depression - epidemiology
Depression - psychology
Female
Humans
Male
Netherlands - epidemiology
Psychiatric Status Rating Scales
Risk Factors
Title 10-year trajectories of depressive symptoms and risk of dementia: a population-based study
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