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Comorbid Depression Is Associated with an Increased Risk of Dementia Diagnosis in Patients with Diabetes: A Prospective Cohort Study

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Abstract

BACKGROUND

Both depression and diabetes have been found to be risk factors for dementia. This study examined whether comorbid depression in patients with diabetes increases the risk for dementia compared to those with diabetes alone.

METHODS

We conducted a prospective cohort study of 3,837 primary care patients with diabetes (mean age 63.2 ± 13.2 years) enrolled in an HMO in Washington State. The Patient Health Questionnaire (PHQ-9) was used to assess depression at baseline, and ICD-9 diagnoses for dementia were used to identify cases of dementia. Cohort members with no previous ICD-9 diagnosis of dementia prior to baseline were followed for a 5-year period. The risk of dementia for patients with both major depression and diabetes at baseline relative to patients with diabetes alone was estimated using cause-specific Cox proportional hazard regression models that adjusted for age, gender, education, race/ethnicity, diabetes duration, treatment with insulin, diabetes complications, nondiabetes-related medical comorbidity, hypertension, BMI, physical inactivity, smoking, HbA1c, and number of primary care visits per month.

RESULTS

Over the 5-year period, 36 of 455 (7.9%) patients with major depression and diabetes (incidence rate of 21.5 per 1,000 person-years) versus 163 of 3,382 (4.8%) patients with diabetes alone (incidence rate of 11.8 per 1,000 person-years) had one or more ICD-9 diagnoses of dementia. Patients with comorbid major depression had an increased risk of dementia (fully adjusted hazard ratio 2.69, 95% CI 1.77, 4.07).

CONCLUSIONS

Patients with major depression and diabetes had an increased risk of development of dementia compared to those with diabetes alone. These data add to recent findings showing that depression was associated with an increased risk of macrovascular and microvascular complications in patients with diabetes.

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References

  1. Cankurtaran M, Yavuz BB, Cankurtaran ES, Halil M, Ulger Z, Ariogul S. Risk factors and type of dementia: vascular or Alzheimer? Arch Gerontol Geriatr. 2008;47:25–34.

    Article  PubMed  Google Scholar 

  2. Jorm AF. Is depression a risk factor for dementia or cognitive decline? A review. Gerontology. 2000;46:219–27.

    Article  CAS  PubMed  Google Scholar 

  3. Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry. 2006;63:530–8.

    Article  PubMed  Google Scholar 

  4. Butters MA, Young JB, Lopez O, et al. Pathways linking late-life depression to persistent cognitive impairment and dementia. Dialogues Clin Neurosci. 2008;10:345–57.

    PubMed  Google Scholar 

  5. Corsentino EA, Sawyer K, Sachs-Ericsson N, Blazer DG. Depressive symptoms moderate the influence of the apolipoproteine epsilon4 allele on cognitive decline in a sample of community dwelling older adults. Am J Geriatr Psychiatry. 2009;17:155–65.

    Article  PubMed  Google Scholar 

  6. Irie F, Masaki KH, Petrovitch H, et al. Apolipoprotein ε4 allele genotype and the effect of depressive symptoms on the risk of dementia in men: the Honolulu-Asia aging study. Arch Gen Psychiatry. 2008;65:906–12.

    Article  PubMed  Google Scholar 

  7. Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry. 2001;49:1023–39.

    Article  CAS  PubMed  Google Scholar 

  8. Taylor CB, Conrad A, Wilhelm FH, et al. Psychophysiological and cortisol responses to psychological stress in depressed and nondepressed older men and women with elevated cardiovascular disease risk. Psychosom Med. 2006;68:538–46.

    Article  CAS  PubMed  Google Scholar 

  9. Musselman DL, Marzec U, Davidoff M, et al. Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatment. Depress Anxiety. 2002;15:91–101.

    Article  CAS  PubMed  Google Scholar 

  10. Leonard BE. Inflammation, depression and dementia: are they connected? Neurochem Res. 2007;32:1749–56.

    Article  CAS  PubMed  Google Scholar 

  11. Wassertheil-Smoller S, Shumaker S, Ockene J, et al. Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI). Arch Intern Med. 2004;164:289–98.

    Article  PubMed  Google Scholar 

  12. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2006;5:64–74.

    Article  PubMed  Google Scholar 

  13. Kloppenborg RP, van den Berg E, Kappelle LJ, Biessels GJ. Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review. Eur J Pharmacol. 2008;585:97–108.

    Article  CAS  PubMed  Google Scholar 

  14. Messier G, Gagnon M. Cognitive decline assocaited with dementia and type 2 diabetes: the interplay on risk factors. Diabetologia. 2009;52:2471–4.

    Article  CAS  PubMed  Google Scholar 

  15. Watson GS, Craft S. The role of insulin resistance in the pathogenesis of Alzheimer's disease: implications for treatment. CNS Drugs. 2003;17:27–45.

    Article  CAS  PubMed  Google Scholar 

  16. Ali S, Stone MA, Peters JL, Davies MJ, Khunti K. The prevalence of co-morbid depression in adults with Type 2 diabetes: a systematic review and meta-analysis. Diabet Med. 2006;23:1165–73.

    Article  CAS  PubMed  Google Scholar 

  17. Lin EH, Katon W, Von Korff M, et al. Relationship of depression and diabetes self-care, medication adherence, and preventive care. Diabetes Care. 2004;27:2154–60.

    Article  PubMed  Google Scholar 

  18. Katon WJ, Lin EH, Russo J, et al. Cardiac risk factors in patients with diabetes mellitus and major depression. J Gen Intern Med. 2004;19:1192–9.

    Article  PubMed  Google Scholar 

  19. Black SA, Markides KS, Ray LA. Depression predicts increased incidence of adverse health outcomes in older Mexican Americans with type 2 diabetes. Diabetes Care. 2003;26:2822–8.

    Article  PubMed  Google Scholar 

  20. Lin EH, Rutter CM, Katon W, et al. Depression and advanced complications of diabetes: a prospective cohort study. Diabetes Care. Nov 23, 2009 [Epub].

  21. McCulloch DK, Price MJ, Hindmarsh M, Wagner EH. A population-based approach to diabetes management in a primary care setting: early results and lessons learned. Eff Clin Pract. 1998;1:12–22.

    CAS  PubMed  Google Scholar 

  22. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606–13.

    Article  CAS  PubMed  Google Scholar 

  23. Wittkampf KA, Naeije L, Schene AH, Huyser J, van Weert HC. Diagnostic accuracy of the mood module of the patient health questionnaire: a systematic review. Gen Hosp Psychiatry. 2007;29:388–95.

    Article  PubMed  Google Scholar 

  24. Toobert DJ, Hampson SE, Glasgow RE. The summary of diabetes self-care activities measure: results from seven studies and a revised scale. Diabetes Care. 2000;23:943–50.

    Article  CAS  PubMed  Google Scholar 

  25. Hu FB, Stampfer MJ, Solomon C, et al. Physical activity and risk for cardiovascular events in diabetic women. Ann Intern Med. 2001;134:96–105.

    CAS  PubMed  Google Scholar 

  26. Young BA, Lin E, Von Korff M, et al. Diabetes complications severity index and risk of mortality, hospitalization, and healthcare utilization. Am J Manag Care. 2008;14:15–23.

    PubMed  Google Scholar 

  27. Fishman PA, Goodman MJ, Hornbrook MC, Meenan RT, Bachman DJ, O'Keeffe Rosetti MC. Risk adjustment using automated ambulatory pharmacy data: the RxRisk model. Med Care. 2003;41:84–99.

    Article  PubMed  Google Scholar 

  28. Simon G, Katon W, Lin E, et al. Diabetes complications and depression as predictors of health care costs. Gen Hosp Psychiatry. 2005;27:344–51.

    Article  PubMed  Google Scholar 

  29. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009;301:1565–72.

    Article  CAS  PubMed  Google Scholar 

  30. Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP Jr, Yaffe K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ. 2005;330:1360.

    Article  PubMed  Google Scholar 

  31. Taylor DH Jr, Fillenbaum GG, Ezell ME. The accuracy of medicare claims data in identifying Alzheimer's disease. J Clin Epidemiol. 2002;55:929–37.

    Article  PubMed  Google Scholar 

  32. Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med. 2007;26:2389–430.

    Article  CAS  PubMed  Google Scholar 

  33. Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE. Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care. 2000;23:934–42.

    Article  CAS  PubMed  Google Scholar 

  34. Katon W, von Korff M, Ciechanowski P, et al. Behavioral and clinical factors associated with depression among individuals with diabetes. Diabetes Care. 2004;27:914–20.

    Article  PubMed  Google Scholar 

  35. Peavy GM, Lange KL, Salmon DP, et al. The effects of prolonged stress and APOE genotype on memory and cortisol in older adults. Biol Psychiatry. 2007;62:472–8.

    Article  CAS  PubMed  Google Scholar 

  36. Lee BK, Glass TA, McAtee MJ, et al. Associations of salivary cortisol with cognitive function in the Baltimore memory study. Arch Gen Psychiatry. 2007;64:810–8.

    Article  CAS  PubMed  Google Scholar 

  37. Elder GA, De Gasperi R, Gama Sosa MA. Research update: neurogenesis in adult brain and neuropsychiatric disorders. Mt Sinai J Med. 2006;73:931–40.

    PubMed  Google Scholar 

  38. Videbech P, Ravnkilde B. Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry. 2004;161:1957–66.

    Article  PubMed  Google Scholar 

  39. Sheline YI, Sanghavi M, Mintun MA, Gado MH. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci. 1999;19:5034–43.

    CAS  PubMed  Google Scholar 

  40. Bell-McGinty S, Butters MA, Meltzer CC, Greer PJ, Reynolds CF 3rd, Becker JT. Brain morphometric abnormalities in geriatric depression: long-term neurobiological effects of illness duration. Am J Psychiatry. 2002;159:1424–7.

    Article  PubMed  Google Scholar 

  41. Skoog I, Lernfelt B, Landahl S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996;347:1141–5.

    Article  CAS  PubMed  Google Scholar 

  42. Breteler MM, Claus JJ, van Duijn CM, Launer LJ, Hofman A. Epidemiology of Alzheimer's disease. Epidemiol Rev. 1992;14:59–82.

    CAS  PubMed  Google Scholar 

  43. Van der Kooy K, van Hout H, Marwijk H, Marten H, Stehouwer C, Beekman A. Depression and the risk for cardiovascular diseases: systematic review and meta analysis. Int J Geriatr Psychiatry. 2007;22:613–26.

    Article  PubMed  Google Scholar 

  44. Salaycik KJ, Kelly-Hayes M, Beiser A, et al. Depressive symptoms and risk of stroke: the Framingham Study. Stroke. 2007;38:16–21.

    Article  PubMed  Google Scholar 

  45. Lin E, Rutter C, Katon W, et al. Depression and adverse outcomes of diabetes. Diabetes Care. In Press.

  46. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA. 1997;277:813–7.

    Article  CAS  PubMed  Google Scholar 

  47. Lim A, Tsuang D, Kukull W, et al. Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series. J Am Geriatr Soc. 1999;47:564–9.

    CAS  PubMed  Google Scholar 

  48. Heyman A, Fillenbaum GG, Welsh-Bohmer KA, et al. Cerebral infarcts in patients with autopsy-proven Alzheimer's disease: CERAD, part XVIII. Consortium to establish a registry for Alzheimer's disease. Neurology. 1998;51:159–62.

    CAS  PubMed  Google Scholar 

  49. Korcizyn A, Haperin I. Depression and dementia. J Neurol Sci. April 3, 2009 (epub).

  50. Zubenko GS, Zubenko WN, McPherson S, et al. A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease. Am J Psychiatry. 2003;160:857–66.

    Article  PubMed  Google Scholar 

  51. Steffens DC, Krishnan KR, Crump C, Burke GL. Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study. Stroke. 2002;33:1636–44.

    Article  PubMed  Google Scholar 

  52. Teodorczuk A, O'Brien JT, Firbank MJ, et al. White matter changes and late-life depressive symptoms: longitudinal study. Br J Psychiatry. 2007;191:212–7.

    Article  CAS  PubMed  Google Scholar 

  53. Pantoni L, Leys D, Fazekas F, et al. Role of white matter lesions in cognitive impairment of vascular origin. Alzheimer Dis Assoc Disord. 1999;13(Suppl 3):S49–54.

    Article  PubMed  Google Scholar 

  54. Krishnan MS, O'Brien JT, Firbank MJ, et al. Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study. Int J Geriatr Psychiatry. 2006;21:983–9.

    Article  PubMed  Google Scholar 

  55. Katon WJ, Von Korff M, Lin EH, et al. The Pathways Study: a randomized trial of collaborative care in patients with diabetes and depression. Arch Gen Psychiatry. 2004;61:1042–9.

    Article  PubMed  Google Scholar 

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Acknowledgements

This study was supported by NIMH R01 MH073686 (Von Korff) and NIMH K24 MH069741 (Katon). The authors would like to acknowledge Jürgen Unützer, MD, MPH, for providing critiques for this manuscript.

Conflicts of Interest

Dr. Katon had received honorariums for lectures from Wyeth, Eli Lilly, Forest, and Pfizer pharmaceutical companies and serves on the Advisory Board for Eli Lilly and Wyeth. Dr. Von Korff has submitted a grant to Johnson & Johnson, but its award status is still pending. Dr. Paul Ciechanowski is CEO and founder of Same Page, Inc., a consulting company providing services for improving patient-provider relationships. Dr. Lin has received honorariums from Health Star Communications and Prescott Medical.

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Authors and Affiliations

  1. Department of Psychiatry & Behavioral Sciences, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356560, Seattle, WA, 98195-6560, USA

    Wayne J. Katon MD & Paul Ciechanowski MD, MPH

  2. Group Health Research Institute, Seattle, WA, USA

    Elizabeth H. B. Lin MD, MPH, Evette Ludman PhD, Carolyn Rutter PhD, Malia Oliver BA & Michael Von Korff ScD

  3. Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA

    Lisa H. Williams MD, MS & Paul K. Crane MD, MPH

  4. Epidemiologic Research and Information Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA

    Lisa H. Williams MD, MS

  5. Department of Epidemiology, University of Washington School of Medicine, Seattle, WA, USA

    Susan R. Heckbert MD, PhD

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  1. Wayne J. Katon MD
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  2. Elizabeth H. B. Lin MD, MPH
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  10. Michael Von Korff ScD
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Correspondence to Wayne J. Katon MD.

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Katon, W.J., Lin, E.H.B., Williams, L.H. et al. Comorbid Depression Is Associated with an Increased Risk of Dementia Diagnosis in Patients with Diabetes: A Prospective Cohort Study. J GEN INTERN MED 25, 423–429 (2010). https://doi.org/10.1007/s11606-009-1248-6

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  • DOI: https://doi.org/10.1007/s11606-009-1248-6

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