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Depressive symptoms and risk of dementia: The Framingham Heart Study

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Saczynski, J.S., Beiser, A., Seshadri, S., Auerbach, S., Wolf, P.A., Au, R.·2010·Neurology
DOI 10.1212/wnl.0b013e3181e62138PMC PMC2906404
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Abstract

OBJECTIVES: Depression may be associated with an increased risk for dementia, although results from population-based samples have been inconsistent. We examined the association between depressive symptoms and incident dementia over a 17-year follow-up period. METHODS: In 949 Framingham original cohort participants (63.6% women, mean age = 79), depressive symptoms were assessed at baseline (1990-1994) using the 60-point Center for Epidemiologic Studies Depression Scale (CES-D). A cutpoint of > or = 16 was used to define depression, which was present in 13.2% of the sample. Cox proportional hazards models adjusting for age, sex, education, homocysteine, and APOE epsilon4 examined the association between baseline depressive symptoms and the risk of dementia and Alzheimer disease (AD). RESULTS: During the 17-year follow-up period, 164 participants developed dementia; 136 of these cases were AD. A total of 21.6% of participants who were depressed at baseline developed dementia compared with 16.6% of those who were not depressed. Depressed participants (CES-D >/=16) had more than a 50% increased risk for dementia (hazard ratio [HR] 1.72, 95% confidence interval [CI] 1.04-2.84, p = 0.035) and AD (HR 1.76, 95% CI 1.03-3.01, p = 0.039). Results were similar when we included subjects taking antidepressant medications as depressed. For each 10-point increase on the CES-D, there was significant increase in the risk of dementia (HR 1.46, 95% CI 1.18-1.79, p < 0.001) and AD (HR 1.39, 95% CI 1.11-1.75, p = 0.005). Results were similar when we excluded persons with possible mild cognitive impairment. CONCLUSIONS: Depression is associated with an increased risk of dementia and AD in older men and women over 17 years of follow-up.

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  • Depression is a predisposing factor for the development of incident dementia.

    “Recently, several important prospective studies have demonstrated that depression is a predisposing factor for the development of incident dementia (43–45).”

    From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [45]

    The Discussion reports that depression was associated with a significantly increased risk of incident dementia over 17 years and describes it as a risk factor. But it also says it is unclear whether depression increases dementia risk or depressive symptoms are an early sign of dementia pathology. The claim's assertion that depression is a predisposing factor is stronger than the paper establishes. (LLM, conf=0.85)

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  1. DISCLOSURE Dr. Saczynski reports no disclosures. Dr. Beiser receives royalties from the publication of Introductory Applied Statistics (Brooks Cole, 2005) and receives research support from the NIH (NINDS 2 R01NS017950-28 [biostatisti- cian], NIA 5 R01 AG08122 [biostatistician], NIA 2 R01 AG16495 [biostat- istician], NINDS 1 R01 AG033040-01 [], and NHLBI R01 HL093029-01A1 [biostatistician]). Dr. Seshadri serves as an Associate Editor of the Journal of Alzheimer's Disease and receives research support from the NIH (NIA R01 AG08122 [investigator], NINDS R01 NS017950-28 [inves- tigator], NIA R01 AG16495 [investigator], NIA 1 R01 AG033040-01 [in- vestigator], NIA P30AG013846 [investigator], NINDS R01 NS062877-01
  2. and NHLBI R01HL093029 [PI of subcontract]). Dr. Auerbach has served on a scientific advisory board for and has received speaker honoraria from Forest Laboratories, Inc. and has served on speakers' bureaus for Forest Labo- ratories, Inc. and Takeda Pharmaceutical Company Limited. Dr. Wolf re- ceives royalties from the publication of the 5th edition of Stroke: Pathophysiology, Diagnosis, and Management (Elsevier, 2008) and receives re- search support from the NIH (NHLBI N01-HC-25195 [PI], NINDS 2 R01 NS 17950
  3. Jorm AF. History of depression as a risk factor for demen- tia: an updated review. Aust NZ J Psychiatry 2001;35: 776 -781.
  4. Jorm AF, van Duijn CM, Chandra V, et al. Psychiatric history and related exposures as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies: EURODEM Risk Factors Research Group. Int J Epide- miol 1991;20:S43-S47.
  5. Speck CE, Kukull WA, Brenner DE, et al. History of de- pression as a risk factor for Alzheimer's disease. Epidemiol- ogy 1995;6:366 -369.
  6. Green RC, Cupples LA, Kurz A, et al. Depression as a risk factor for Alzheimer disease: the MIRAGE study. Arch Neurol 2003;60:753-759.
  7. Wilson RS, Barnes LL, Mendes de Leon CF, et al. Depres- sive symptoms, cognitive decline, and risk of AD in older persons. Neurology 2002;59:364 -370.
  8. Devanand DP, Sano M, Tang M-X, et al. Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community. Arch Gen Psychiatry 1996;53:175-182.
  9. Berger AK, Fratiglioni L, Forsell Y, Winblad B, Backman L. The occurrence of depressive symptoms in the preclini- cal phase of AD: a population-based study. Neurology 1999;53:1998 -2002.
  10. Chen P, Ganguli M, Mulsant BH, DeKosky ST. The tem- poral relationship between depressive symptoms and de- mentia: a community-based prospective study. Arch Gen Psychiatry 1999;56:261-266.
  11. Becker JT, Chang YF, Lopez OL, et al. Depressed mood is not a risk factor for incident dementia in a community- based cohort. Am J Geriatr Psychiatry 2009;17:653-663.
  12. Henderson AS, Korten AE, Jacomb PA, et al. The course of depression in the elderly: a longitudinal community- based study in Australia. Psychol Med 1997;27:119 -129.
  13. Geerlings MI, Bouter LM, Schoevers R, et al. Depression and risk of cognitive decline and Alzheimer's disease: re- sults of two prospective community-based studies in the Netherlands. Br J Psychiatry 2000;176:568 -575.
  14. Fuhrer R, Dufouil C, Dartigues J. Exploring sex differ- ences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID Study. J Am Geriatr Soc 2003;51:1055-1063.
  15. Forno G, Palermo M, Donohue J, Karagiozis H, Zonder- man A, Kawas C. Depressive symptoms, sex, and risk for Alzheimer's disease. Ann Neurol 2005;57:381-387.
  16. Farmer ME, White LR, Kittner SJ, et al. Neuropsycholog- ical test performance in Framingham: a descriptive study. Psychol Rep 1987;60:1023-1040.
  17. Radloff L. The CES-D Scale: a self-report depression scale for research in the general population. Appl Psychol Meth- ods 1977;1:385-401.
  18. Seshadri S, Beiser A, Kelly-Hayes M, et al. The lifetime risk of stroke: estimates from the Framingham Study. Stroke 2006;37:345-350.
  19. Berg L. Clinical Dementia Rating (CDR). Psychopharma- col Bull 1988;24:637-639.
  20. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34: 939 -944.
  21. Araki A, Sako Y. Determination of free and total homocys- teine in human plasma by high-performance liquid chro- matography with fluorescence detection. J Chromatogr 1987;422:43-52.
  22. Selhub J, Jacques PF, Wilson PWF, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocystinemia in an elderly population. JAMA 1993; 270:2693-2698.
  23. Ordovas JM, Litwack-Klein L, Wilson PW, Schaefer MM, Schaefer EJ. Apolipoprotein E isoform phenotyping meth- odology and population frequency with identification of apoE1 and apoE5 isoforms. J Lipid Res 1987;28:371-380.
  24. Welty FK, Lahoz C, Tucker KL, Ordovas JM, Wilson PWF, Schaefer EJ. Frequency of ApoB and ApoE gene mutations as causes of hypobetalipoproteinemia in the Fra- mingham offspring population. Arterioscler Thromb Vasc Biol 1998;18:1745-1751.
  25. Irie F, Masaki KH, Petrovitch H, et al. Apolipoprotein E ⑀4 allele genotype and the effect of depressive symptoms on the risk of dementia in men: the Honolulu-Asia Aging Study. Arch Gen Psychiatry 2008;65:906 -912.
  26. Dal Forno G, Palermo MT, Donohue JE, Karagiozis H, Zonderman AB, Kawas CH. Depressive symptoms, sex, and risk for Alzheimer's disease. Ann Neurol 2005;57:381-387.
  27. Leonard BE. Inflammation, depression and dementia: are they connected? Neurochem Res 2007;32:1749 -1756.
  28. Miller GE, Stetler CA, Carney RM, Freedland KE, Banks WA. Clinical depression and inflammatory risk markers for coronary heart disease. Am J Cardiol 2002;90:1279 -1283.
  29. Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 2009;5:311-322.
  30. Tsai S-J. Brain-derived neurotrophic factor: a bridge be- tween major depression and Alzheimer's disease? Med Hy- poth 2003;61:110 -113.
  31. Alexopoulos GS, Meyers BS, Young RC, Campbell S, Sil- bersweig D, Charlson M. 'Vascular depression' hypothesis. Arch Gen Psychiatry 1997;54:915-922.
  32. Steffens DC, Helms MJ, Krishnan KR, Burke GL. Cere- brovascular disease and depression symptoms in the Car- diovascular Health Study. Stroke 1999;30:2159 -2166.
  33. Tiemeier H, Breteler MM, van Popele NM, Hofman A, Witteman JC. Late-life depression is associated with arte- rial stiffness: a population-based study. J Am Geriatr Soc 2003;51:1105-1110.
  34. Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MMB. Vitamin B12, folate, and homocys- teine in depression: the Rotterdam Study. Am J Psychiatry 2002;159:2099 -2101.
  35. Penninx BWJH, Guralnik JM, Ferrucci L, Fried LP, Allen RH, Stabler SP. Vitamin B12 deficiency and depression in physically disabled older women: epidemiologic evidence from the Women's Health and Aging Study. Am J Psychi- atry 2000;157:715-721.
  36. van Gool CH, Kempen GI, Penninx BW, Deeg DJ, Beek- man AT, van Eijk JT. Relationship between changes in depressive symptoms and unhealthy lifestyles in late mid- dle aged and older persons: results from the Longitudinal Aging Study Amsterdam. Age Ageing 2003;32:81-87.
  37. Lampinen P, Heikkinen R-L, Ruoppila I. Changes in in- tensity of physical exercise as predictors of depressive symptoms among older adults: an eight-year follow-up. Prev Med 2000;30:371-380.
  38. Saczynski JS, Pfeifer LA, Masaki K, et al. The effect of social engagement on incident dementia: the Honolulu- Asia Aging Study. Am J Epidemiol 2006;163:433-440.

Cited by

Sorted by citations

Authors
Saczynski, J. S., Beiser, A., Seshadri, S., Auerbach, S., Wolf, P. A., & Au, R.
Affiliations
Boston University (US)
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-07-06
Volume
75
Issue
1
Pages
35-41
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0b013e3181e62138
PMC
PMC2906404
OpenAlex
W2072983755
Cited by
488
References
3
Citations by year
2026: 21 · 2025: 30 · 2024: 28 · 2023: 22 · 2022: 26 · 2021: 39 · 2020: 32 · 2019: 21 · 2018: 30 · 2017: 32 · 2016: 26 · 2015: 34 · 2014: 31 · 2013: 37 · 2012: 34
FWCI
25.58
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship@UMassChan (submittedVersion)
Funders
  • National Institutes of Health (n01hc25195-41-0-1)
  • National Institute on Aging (K01AG033643, AG-16495, R01-AG-16495, R01AG029451, R01AG031287, 1-R01-AG16495, R01 AG08122, 2 R01 AG16495, AG08122, R01AG033040, R01AG016495, 5-R01-AG-08122, P30AG013846, R01AG033193, R01AG008122)
  • National Heart, Lung, and Blood Institute (R01HL083197, N01‐HC25195, 1-R01-HL083197, R01HL093029)
  • National Institute of Neurological Disorders and Stroke (R01NS062877, NS17950, 2 R01 NS 17950, R01NS017950)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
Keywords
depressive symptoms, dementia risk, Alzheimer's disease, older adults, CES-D depression scale, antidepressant use, mild cognitive impairment, APOE ε4, homocysteine
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Coronary Disease, Dementia, Depression, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Risk Factors, Cohort Studies

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