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Cited by 95Dementia and Cognitive Impairment ResearchAging, Health, and DisabilityTreatment of Major Depression

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Depressive Symptoms in the Elderly—An Early Symptom of Dementia? A Systematic Review

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Wiels, Wietse, Baeken, Chris, Engelborghs, Sebastiaan·2020·Frontiers in Pharmacology
DOI 10.3389/fphar.2020.00034PMC PMC7020568
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Abstract

BACKGROUND: Depression and dementia are common incapacitating diseases in old age. The exact nature of the relationship between these conditions remains unclear, and multiple explanations have been suggested: depressive symptoms may be a risk factor for, a prodromal symptom of, or a coincidental finding in dementia. They may even be unrelated or only connected through common risk factors. Multiple studies so far have provided conflicting results. OBJECTIVES: To determine whether a systematic literature review can clarify the nature of the relation between depressive symptoms and dementia. METHODS: Using the Patient/Problem/Population, Intervention, Comparator, Outcome or PICO paradigm, a known framework for framing healthcare and evidence questions, we formulated the question "whether depressive symptoms in cognitively intact older adults are associated with a diagnosis of dementia later in life." We performed a systematic literature review of MEDLINE and PsycINFO in November 2018, looking for prospective cohort studies examining the aforementioned question. RESULTS: We critically analyzed and listed 31 relevant papers out of 1,656 and grouped them according to the main hypothesis they support: depressive symptoms as a risk factor, not a risk factor, a prodromal symptom, both, or some specific other hypothesis. All but three studies used clinical diagnostic criteria for dementia alone (i.e., no biomarkers or autopsy confirmation). Several studies contain solid arguments for the hypotheses they support, yet they do not formally contradict other findings or suggested explanations and are heterogeneous. CONCLUSIONS: The exact nature of the relationship between depressive symptoms and dementia in the elderly remains inconclusive, with multiple studies supporting both the risk factor and prodromal hypotheses. Some provide arguments for common risk factors. It seems unlikely that there is no connection at all. We conclude that at least in a significant part of the patients, depressive symptoms and dementia are related. This may be due to common risk factors and/or depressive symptoms being a prodromal symptom of dementia and/or depression being a risk factor for dementia. These causal associations possibly overlap in some patients. Further research is warranted to develop predictive biomarkers and to develop interventions that may attenuate the risk of "conversion" from depressive symptoms to dementia in the elderly.

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  1. Alexoupoulos, 1993, The course of geriatric depression with “reversible dementia”: a controlled study, Am. J. Psychiatry, 150, 1693, 10.1176/ajp.150.11.1693 · DOI
  2. Almeida, 2010, Depression antidepressant use and mortality in later life: the health in men study, PloS One, 5, 10.1371/journal.pone.0011266 · DOI
  3. 2013, The Global impact of Dementia 2013-2050 – Policy Brief for Heads of Government.
  4. Barnes, 2011, The projected effect of risk factor reduction on Alzheimer’s disease prevalence, Lancet Neurol., 10, 819, 10.1016/S1474-4422(11)70072-2 · DOI
  5. Bassuk, 1998, Depressive symptomatology and incident cognitive decline in an elderly community sample, Arch. Gen. Psychiatry, 55, 1073, 10.1001/archpsyc.55.12.1073 · DOI
  6. Becker, 2009, Depressed mood is not a risk factor for incident dementia in a community-based cohort, Am. J. Geriatr. Psychiatry, 17, 653, 10.1097/JGP.0b013e3181aad1fe · DOI
  7. Bennet, 2014, Depression and dementia: cause, consequence or coincidence, Maturitas, 79, 184, 10.1016/j.maturitas.2014.05.009 · DOI · Paper page
  8. Blasko, 2010, Plasma amyloid beta-42 independently predicts both late-onset depression and Alzheimer disease, Am. J. Geriatr. Psychiatry, 18, 973, 10.1097/JGP.0b013e3181df48be · DOI
  9. Brauer, 2019, Trazodone use and risk of dementia: A population-based cohort study, PloS Med., 16, 10.1371/journal.pmed.1002728 · DOI
  10. Brayne, 1999, Estimating the true extent of cognitive decline in the old old, J. Am. Geriatrics Soc., 47, 1283, 10.1111/j.1532-5415.1999.tb07426.x · DOI
  11. Brodaty, 2012, Neuropsychiatric symptoms in older people with and without cognitive impairment, J. Alzheimers Dis., 31, 411, 10.3233/JAD-2012-120169 · DOI
  12. Burke, 2016, Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer’s disease: dementia, Int. Psychogeriatr., 28, 1409, 10.1017/S1041610216000405 · DOI
  13. Byers, 2011, Depression and risk of developing dementia, Nat. Rev. Neurol., 7, 323, 10.1038/nrneurol.2011.60 · DOI · Paper page
  14. Carpenter, 2008, Reaction to a dementia diagnosis in individuals with Alzheimer’s Disease and mild cognitive impairment, J. Am. Geriatrics Soc., 56, 405, 10.1111/j.1532-5415.2007.01600.x · DOI
  15. Chen, 1999, The temporal relationship between depressive symptoms and dementia: a community-based prospective study, Arch. Gen. Psychiatry, 56, 261, 10.1001/archpsyc.56.3.261 · DOI · Paper page
  16. Chu, 2018, Electroconvulsive therapy and risk of dementia-a nationwide cohort study in Taiwan, Front. Psychiatry, 9, 10.3389/fpsyt.2018.00397 · DOI
  17. Dal Forno, 2015, Depressive symptoms, sex, and risk for Alzheimer’s disease, Ann. Neurol., 57, 381, 10.1002/ana.20405 · DOI
  18. Devanand, 1996, Depressed mood and the incidence of Alzheimer’s disease in the elderly living in the community, Arch. Gen. Psychiatry, 53, 175, 10.1001/archpsyc.1996.01830020093011 · DOI
  19. Donovan, 2018, Longitudinal association of amyloid beta and anxious-depressive symptoms in cognitively normal older adults, Am. J. Psychiatry, 175, 530, 10.1176/appi.ajp.2017.17040442 · DOI · Paper page
  20. Dufouil, 1996, Longitudinal analysis of the association between depressive symptomatology and cognitive deterioration, Am. J. Epidemiol., 144, 634, 10.1093/oxfordjournals.aje.a008974 · DOI
  21. Elahi, 2017, A clinicopathological approach to the diagnosis of dementia, Nat. Rev. Neurol., 13, 457, 10.1038/nrneurol.2017.96 · DOI
  22. Enache, 2011, Depression in dementia: epidemiology, mechanisms, and treatment, Curr. Opin. Psychiatry, 24, 461, 10.1097/YCO.0b013e32834bb9d4 · DOI
  23. Ezzati, 2019, Depressive symptoms predict incident dementia in a community sample of older adults: results from the einstein aging study, J. Geriatric Psychiatry Neurol., 32, 97, 10.1177/0891988718824036 · DOI
  24. Fuhrer, 2003, Exploring sex differences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID Study, J. Am. Geriatrics Soc., 51, 1055, 10.1046/j.1532-5415.2003.51352.x · DOI
  25. Gatz, 2005, Do depressive symptoms predict Alzheimer’s disease and dementia, J. Gerontol A Biol. Sci. Med. Sci., 60, 744, 10.1093/gerona/60.6.744 · DOI
  26. Geda, 2014, Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a population-based study, Am. J. Psychiatry, 171, 572, 10.1176/appi.ajp.2014.13060821 · DOI
  27. Geerlings, 2000, Depression and risk of cognitive decline and Alzheimer’s disease: results of two prospective community-based studies in the netherlands, Br. J. Psychiatry, 176, 568, 10.1192/bjp.176.6.568 · DOI
  28. Geerlings, 2008, History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease, Neurology, 70, 1258, 10.1212/01.wnl.0000308937.30473.d1 · DOI · Paper page
  29. Hall, 2014, Late-life depression in the primary care setting: challenges, collaborative care, and prevention, Maturitas, 79, 147, 10.1016/j.maturitas.2014.05.026 · DOI
  30. Harrington, 2017, Amyloid burden and incident depressive symptoms in cognitively normal older adults, Int. J. Geriatr. Psychiatry, 32, 455, 10.1002/gps.4489 · DOI
  31. Irie, 2008, Apolipoprotein E epsilon4 allele genotype and the effect of depressive symptoms on the risk of dementia in men: the Honolulu-Asia aging study, Arch. Gen. Psychiatry, 65, 906, 10.1001/archpsyc.65.8.906 · DOI
  32. Jacob, 2017, Risk of dementia in German patients treated with antidepressants in general or psychiatric practices, Int. J. Clin. Pharmacol. Ther., 55, 322, 10.5414/CP202754 · DOI · Paper page
  33. Jansen, 2015, Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis, JAMA, 313, 1924, 10.1001/jama.2015.4668 · DOI · Paper page
  34. Köhler, 2011, Depressive symptoms and risk for dementia: a 9-year follow-up of the maastricht aging study, Am. J. Geriatr. Psychiatry, 19, 902, 10.1097/JGP.0b013e31821f1b6a · DOI · Paper page
  35. Kaup, 2016, Trajectories of depressive symptoms in older adults and risk of dementia, JAMA Psychiatry, 73, 525, 10.1001/jamapsychiatry.2016.0004 · DOI · Paper page
  36. Kim, 2010, Apolipoprotein e4 genotype and depressive symptoms as risk factors for dementia in an older korean population, Psychiatry Invest., 7, 135, 10.4306/pi.2010.7.2.135 · DOI
  37. Lam, 2014, Cognitive dysfunction in major depressive disorder: effects on psychosocial functioning and implications for treatment, Can. J. Psychiatry, 59, 649, 10.1177/070674371405901206 · DOI
  38. Lenoir, 2011, Depression history, depressive symptoms, and incident dementia: the 3C Study, J. Alzheimers Dis., 26, 27, 10.3233/JAD-2011-101614 · DOI
  39. Li, 2011, Temporal relationship between depression and dementia: findings from a large community-based 15-year follow-up study, Arch. Gen. Psychiatry, 68, 970, 10.1001/archgenpsychiatry.2011.86 · DOI
  40. Lindsay, 2002, Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian study of health and aging, Am. J. Epidemiol., 156, 445, 10.1093/aje/kwf074 · DOI · Paper page
  41. Livingston, 2017, Dementia prevention, intervention, and care, Lancet, 390, 2673, 10.1016/S0140-6736(17)31363-6 · DOI · Paper page
  42. Luppa, 2013, Depression and incident dementia. An 8-year population-based prospective study, PloS One, 8, 10.1371/journal.pone.0059246 · DOI
  43. Mahgoub, 2016, Amyloid hypothesis: is there a role for antiamyloid treatment in late-life depression, Am. J. Geriatr. Psychiatry, 24, 239, 10.1016/j.jagp.2015.12.003 · DOI · Paper page
  44. Mirza, 2016, 10-year trajectories of depressive symptoms and risk of dementia: a population-based study, Lancet Psychiatry, 3, 628, 10.1016/S2215-0366(16)00097-3 · DOI · Paper page
  45. Moher, 2009, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement, BMJ, 339, 10.1136/bmj.b2535 · DOI · Paper page
  46. Mossaheb, 2012, Are specific symptoms of depression predictive of Alzheimer’s dementia, J. Clin. Psychiatry, 73, 1009, 10.4088/JCP.11m06962 · DOI
  47. Ownby, 2006, Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis, Arch. Gen. Psychiatry, 63, 530, 10.1001/archpsyc.63.5.530 · DOI · Paper page
  48. Pálsson, 1999, Depression, cerebral atrophy, cognitive performance and incidence of dementia: population study of 85-year-olds, Br. J. Psychiatry, 174, 249, 10.1192/bjp.174.3.249 · DOI
  49. Palmer, 2007, Predictors of progression from mild cognitive impairment to Alzheimer disease, Neurology, 68, 1596, 10.1212/01.wnl.0000260968.92345.3f · DOI
  50. Patten, 2003, Recall bias and major depression lifetime prevalence soc psychiatry, Psychiatr. Epidemiol., 38, 290, 10.1007/s00127-003-0649-9 · DOI
  51. Peavy, 2007, The effects of prolonged stress and APOE genotype on memory and cortisol in older adults, Biol. Psychiatry, 62, 472, 10.1016/j.biopsych.2007.03.013 · DOI
  52. Petersen, 2018, How early can we diagnose Alzheimer disease (and is it sufficient)? the 2017 wartenberg lecture, Neurology, 91, 395, 10.1212/WNL.0000000000006088 · DOI
  53. Ritchie, 2016, The clinical picture of Alzheimer’s disease in the decade before diagnosis: clinical and biomarker trajectories, J. Clin. Psychiatry, 77, e305, 10.4088/JCP.15m09989 · DOI
  54. Saczynski, 2010, Depressive symptoms and risk of dementia: the Framingham Heart Study, Neurology, 75, 35, 10.1212/WNL.0b013e3181e62138 · DOI · Paper page
  55. Savva, 2009, Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population, Br. J. Psychiatry, 194, 212, 10.1192/bjp.bp.108.049619 · DOI
  56. Simões do Couto, 2016, Depression with melancholic features is associated with higher long-term risk for dementia, J. Affect. Disord., 202, 220, 10.1016/j.jad.2016.05.026 · DOI
  57. Spira, 2012, Depressive symptoms in oldest-old women: risk of mild cognitive impairment and dementia, Am. J. Geriatr. Psychiatry, 20, 1006, 10.1097/JGP.0b013e318235b611 · DOI
  58. Thomas, 2002, Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study, Arch. Gen. Psychiatry, 59, 785, 10.1001/archpsyc.59.9.785 · DOI
  59. van Maurik, 2019, Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project, Alzheimers Res. Ther., 11, 33, 10.1186/s13195-019-0487-y · DOI · Paper page
  60. van Uden, 2016, Late-onset depressive symptoms increase the risk of dementia in small vessel disease, Neurology, 87, 1102, 10.1212/WNL.0000000000003089 · DOI
  61. Verdelho, 2013, Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: the LADIS study, J. Neurol. Neurosurg. Psychiatry, 84, 1250, 10.1136/jnnp-2012-304191 · DOI
  62. Vinkers, 2004, Temporal relation between depression and cognitive impairment in old age: prospective population based study, BMJ, 329, 881, 10.1136/bmj.38216.604664.DE · DOI
  63. Wilson, 2003, Depressive symptoms, clinical AD, and cortical plaques and tangles in older person, Neurology, 61, 1102, 10.1212/01.WNL.0000092914.04345.97 · DOI
  64. Wilson, 2004, Depressive symptoms and cognitive decline in a community population of older persons, J. Neurol. Neurosurg. Psychiatry, 75, 126
  65. Wilson, 2014, Clinical-pathologic study of depressive symptoms and cognitive decline in old age, Neurology, 83, 702, 10.1212/WNL.0000000000000715 · DOI · Paper page
  66. Wilson, 2016, Late-life depression is not associated with dementia-related pathology, Neuropsychology, 30, 135, 10.1037/neu0000223 · DOI · Paper page
  67. Yaffe, 1999, Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study, Arch. Gen. Psychiatry, 56, 425, 10.1001/archpsyc.56.5.425 · DOI · Paper page

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Metadata

Authors
Wiels, W., Baeken, C., & Engelborghs, S.
Affiliations
Vrije Universiteit Brussel (BE)
Corresponding author
Engelborghs, Sebastiaan
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2020-02-07
Volume
11
Pages
34-34
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2020.00034
PMC
PMC7020568
OpenAlex
W3004727685
Cited by
95
References
12
Citations by year
2026: 12 · 2025: 17 · 2024: 16 · 2023: 10 · 2022: 17 · 2021: 13 · 2020: 10
FWCI
1.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Fonds Wetenschappelijk Onderzoek
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Aging, Health, and Disability
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
depressive symptoms, dementia, older adults, prodromal dementia, dementia risk factors, shared risk factors, predictive biomarkers

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