Skip to main content

Advertisement

Log in

How Late-Life Depression Affects Cognition: Neural Mechanisms

  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Late-life depression is a major health problem and a significant cause of dysfunction that warrants closer evaluation and study. In contrast to younger depressed patients, most depressed older adults suffer more severe variants of the disorder, including significant cognitive impairments. These cognitive changes add to the severity of symptoms and disability that older depressed patients face and likely reflect compromise of certain neural circuits, linking cognitive impairment to late-life depression. Studies examining clinical correlates, neuropsychological testing, and functional and anatomic imaging have yielded a clearer understanding of the neural mechanisms underlying cognitive deficits in late-life depression. This article discusses cognitive impairment in geriatric depression and how developing a better understanding of its neural correlates may lead to improved understanding and outcome of this specific disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Murray CJL, Lopez AD, Black R, et al.: The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability From Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Cambridge, MA: Harvard School of Public Health on behalf of the World Health Organization and the World Bank, Harvard University Press; 1996.

    Google Scholar 

  2. NIH consensus conference. Diagnosis and treatment of depression in late life. JAMA 1992, 268:1018–1024.

    Article  Google Scholar 

  3. Koenig HG, Veeraindar G, Shelp F, et al.: Major depression in hospitalized medically ill older men: documentation, management and outcome. Int J Geriatr Psychiatry 1992, 7:25–34.

    Article  Google Scholar 

  4. Parmelee PA, Katz IR, Lawton MP, et al.: Depression and mortality among institutionalized aged. J Gerontol 1992, 47:3–10.

    Google Scholar 

  5. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, edn 4 (text revision). Washington, DC: American Psychiatric Association; 2000.

    Book  Google Scholar 

  6. Beckman AT, Copeland JR, Prince MJ: Review of community prevalence of depression in later life. Br J Psychiatry 1999, 174:307–311.

    Article  Google Scholar 

  7. Charney DS, Reynolds CF, Lewis L, et al.: Depression and bipolar support alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life. Arch Gen Psychiatry 2003, 157:664–672.

    Article  Google Scholar 

  8. Frasure-Smith N, Lesperance F, Talajic M: Depression following myocardial infarction. Impact on 6-month survival. JAMA 1993, 270:1819–1825.

    Article  CAS  PubMed  Google Scholar 

  9. Thomas AJ, Gallagher P, Robinson LJ, et al.: A comparison of neurocognitive impairment in younger and older adults with major depression. Psychol Med 2009, 39:725–733.

    Article  CAS  PubMed  Google Scholar 

  10. Butters MA, Whyte EM, Nebes RD, et al.: The nature and determinants of neuropsychological functioning in late-life depression. Arch Gen Psychiatry 2004, 61:587–595.

    Article  PubMed  Google Scholar 

  11. Boone KB, Lesser IM, Miller BL, et al.: Cognitive functioning in older depressed outpatients: relationships of presence and severity of depression to neuropsychological test scores. Neuropsychology 1995, 9:390–398.

    Article  Google Scholar 

  12. Lichtenberg PA, Ross T, Millis SR, Manning CA: The relationship between depression and cognition in older adults: a cross validation study. J Gerontol B Psychol Sci Soc Sci 1995, 50:P25–P32.

    CAS  PubMed  Google Scholar 

  13. Raskin A: Partialing out the effects of depression and age on cognitive functions: experimental data and methodological issues. In Handbook for Clinical Memory Assessment of Older Adults. Edited by Poon LW. Washington, DC: American Psychological Association; 1986:244–256.

    Chapter  Google Scholar 

  14. La Rue A, Spar J, Hill CD: Cognitive impairment in late-life depression: clinical correlates and treatment implications. J Affect Disord 1986, 11:179–184.

    Article  PubMed  Google Scholar 

  15. Palmer BW, Boone KB, Lesser IM, et al.: Neuropsychological deficits among older depressed patients with predominantly psychological or vegetative symptoms. J Affect Disord 1996, 41:17–24.

    Article  CAS  PubMed  Google Scholar 

  16. Bhalla RK, Butters MA, Mulsant BH, et al.: Persistence of neuropsychological deficits in the remitted state of late-life depression. J Geriatr Psychiatry 2006, 14:419–427.

    Article  Google Scholar 

  17. Alexopoulos GS, Meyers BS, Young RC, et al.: Executive dysfunction and long-term outcomes of geriatric depression. Arch Gen Psychiatry 2000, 57:285–290.

    Article  CAS  PubMed  Google Scholar 

  18. Boone KB, Lesser I, Miller B, et al.: Cognitive function in a mildly to moderately depressed geriatric sample: relationship to chronological age. J Neuropsychiatry Clin Neurosci 1994, 6:267–272.

    CAS  PubMed  Google Scholar 

  19. Lockwood KA, Alexopoulos GS, Kakuma T, et al.: Subtypes of cognitive impairment in depressed older adults. J Geriatr Psychiatry 2000, 8:201–208.

    CAS  Google Scholar 

  20. Rapp MA, Dahlman K, Sano M, et al.: Neuropsychological differences between late-onset and recurrent geriatric major depression. Am J Psychiatry 2005, 162:691–698.

    Article  PubMed  Google Scholar 

  21. Withall A, Harris LM, Cumming SR: The relationship between cognitive function and clinical and functional outcomes in major depressive disorder. Psychol Med 2009, 39:393–402.

    Article  CAS  PubMed  Google Scholar 

  22. Alexopoulos GS, Kiosses DN, Klimsrea S, et al.: Clinical presentation of the “depression-executive dysfunction syndrome” of late life. Am J Geriatr Psychiatry 2002, 10:98–106.

    PubMed  Google Scholar 

  23. Bhalla RK, Butters MA, Becker JT, et al.: Patterns of mild cognitive impairment after treatment of depression in the elderly. Am J Geriatr Psychiatry 2009, 17:308–316.

    Article  PubMed  Google Scholar 

  24. Alexopoulos GS, Meyers BS, Young RC, et al.: The course of geriatric depression with “reversible dementia”: a controlled study. Am J Psychiatry 1993, 150:1693–1699.

    CAS  PubMed  Google Scholar 

  25. Harvey PD, Reichenberg A, Bowie CR: Cognition and aging in psychopathology: focus on schizophrenia and depression. Annu Rev Clin Psychol 2006, 2:389–409.

    Article  PubMed  Google Scholar 

  26. Ownby RL, Crocco E, Acevedo A, et al.: Depression and risk for Alzheimer’s disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry 2006, 63:530–538.

    Article  PubMed  Google Scholar 

  27. Kales HC, Maixner DF, Mellow AM: Cerebrovascular disease and late-life depression. Am J Geriatr Psychiatry 2005, 13:88–98.

    PubMed  Google Scholar 

  28. Greenwald BS, Kramer-Ginsberg E, Krishnan RR, et al.: MRI signal hyperintensities in geriatric depression. Am J Psychiatry 1996, 153:1212–1215.

    CAS  PubMed  Google Scholar 

  29. Steffens DC, Bosworth HB, Provenzale JM, et al.: Subcortical white matter lesions and functional impairment in geriatric depression. Depress Anxiety 2002, 15:23–28.

    Article  PubMed  Google Scholar 

  30. Taylor WD, MacFall JR, Payne ME, et al.: Greater MRI lesion volumes in elderly depressed subjects than in control subjects. Psychiatry Res 2005, 139:1–7.

    Article  PubMed  Google Scholar 

  31. O’Brien JT, Firbank MJ, Krishnan MS, et al.: White matter hyperintensities rather than lacunar infarcts are associated with depressive symptoms in older people: the LADIS study. Am J Geriatr Psychiatry 2006, 14:834–841.

    Article  PubMed  Google Scholar 

  32. Alexopoulos GS, Meyers BS, Young RC, et al.: The “vascular depression” hypothesis. Arch Gen Psychiatry 1997, 54:915–922.

    CAS  PubMed  Google Scholar 

  33. Starkstein SE, Robinson RG, Berthier ML, et al.: Differential mood changes following basal ganglia vs. thalamic lesions. Arch Neurol 1988, 45:725–730.

    CAS  PubMed  Google Scholar 

  34. Lyketsos CG, Treisman GJ, Lipsey JR, et al.: Does stroke cause depression? J Neuropsychiatry Clin Neurosci 1998, 10:103–107.

    CAS  PubMed  Google Scholar 

  35. •• Aizenstein HJ, Butters MA, Wu M, et al.: Altered functioning of the executive control circuit in late-life depression: episodic and persistent phenomena. Am J Geriatr Psychiatry 2009, 17:30–42. This recently published research article links functional neuroimaging to cognitive functioning in depressed older adults.

    Article  PubMed  Google Scholar 

  36. Rajkowaska G, Miguel-Hidalgo LL, Wei J: Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999, 45:1085–1098.

    Article  Google Scholar 

  37. Ongur D, Drevets WC, Price JL: Glial reduction in the prefrontal cortex in mood disorders. Proc Nat Acad Sci U S A 1998, 95:13290–13295.

    Article  CAS  Google Scholar 

  38. Elderkin-Thompson V, Mintz J, Haroon E, et al.: Executive dysfunction and memory in older patients with major and minor depression. Arch Clin Neuropsychol 2007, 22:261–270.

    Article  PubMed  Google Scholar 

  39. Elderkin-Thompson V, Kumar A, Mintz J, et al.: Executive dysfunction and visuospatial ability among depressed elders in a community setting. Arch Clin Neuropsychol 2004, 19:597–611.

    Article  PubMed  Google Scholar 

  40. Delis DC, Kramer JH, Kaplan E, et al.: California Verbal Learning Test: Adult Version. San Antonio, TX: The Psychological Corporation; 1987.

    Google Scholar 

  41. Alexopoulos GS, Kiosses DN, Choi SJ, et al.: Frontal white matter microstructure and treatment response of late-life depression: a preliminary study. Am J Psychiatry 2002, 159:1929–1932.

    Article  PubMed  Google Scholar 

  42. Hickie I, Scott E, Wilhelm K, et al.: Subcortical hyperintensities on magnetic resonance imaging in patients with severe depression-a longitudinal evaluation. Biol Psychiatry 1997, 42:367–374.

    Article  CAS  PubMed  Google Scholar 

  43. Krishna KR, Hays JC, Blazer DG: MRI defined vascular depression. Am J Psychiatry 1997, 154:497–501.

    Google Scholar 

  44. Lesser IM, Mena I, Boone KB, et al.: Reduction of cerebral blood flow in older depressed patients. Arch Gen Psychiatry 1994, 51:677–686.

    CAS  PubMed  Google Scholar 

  45. Drevets WC, Price JL Simpson JR Jr, et al.: Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997, 386:824–827.

    Article  CAS  PubMed  Google Scholar 

  46. De Asis JM, Stern E, Alexopoulos GS, et al.: Hippocampal and anterior cingulate activation in patients with geriatric depression. Am J Psychiatry 2001, 158:1321–1323.

    Article  PubMed  Google Scholar 

  47. •• Sheline YI, Price JL, Vaishnavi SN, et al.: Regional white matter hyperintensity burden in automated segmentation distinguishes late-life depressed subjects from comparison subjects matched for vascular risk factors. Am J Psychiatry 2008, 165:524–532. This recently published study demonstrates a correlation between neuropsychological performance and structural MRI in depressed older adults.

    Article  PubMed  Google Scholar 

  48. Story TJ, Potter GG, Attix DK, et al.: Neurocognitive correlates of response to treatment in late-life depression. Am J Geriatr Psychiatry 2008, 16:752–759.

    Article  PubMed  Google Scholar 

  49. Kalayam B, Alexopoulos GS: Prefrontal dysfunction and treatment response in geriatric depression. Arch Gen Psychiatry 1999, 56:713–718.

    Article  CAS  PubMed  Google Scholar 

  50. Mattis S, Alexopoulos GS, Meyers BS: Neuropsychology of late-onset depression. J Clin Exp Neuropsychol 1993,14:80.

    Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elizabeth A. Crocco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crocco, E.A., Castro, K. & Loewenstein, D.A. How Late-Life Depression Affects Cognition: Neural Mechanisms. Curr Psychiatry Rep 12, 34–38 (2010). https://doi.org/10.1007/s11920-009-0081-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11920-009-0081-2

Keywords

Navigation