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Cognitive Function in Late Life Depression: Relationships to Depression Severity, Cerebrovascular Risk Factors and Processing Speed

      Background

      A number of studies have examined clinical factors linked to worse neuropsychological performance in late life depression (LLD). To understand the influence of LLD on cognition, it is important to determine if deficits in a number of cognitive domains are relatively independent, or mediated by depression- related deficits in a basic domain such as processing speed.

      Methods

      Patients who met DSM-IV criteria for major depression (n = 155) were administered a comprehensive neuropsychological battery of tasks grouped into episodic memory, language, working memory, executive function, and processing speed domains. Multiple regression analyses were conducted to determine contributions of predictor variables to cognitive domains.

      Results

      Age, depression severity, education, race and vascular risk factors all made significant and independent contributions to one or more domains of cognitive function, with all five making independent contributions to processing speed. Age of onset made no independent contribution, after accounting for age and vascular risk factors. Of the five cognitive domains investigated, changes in processing speed were found to most fully mediate the influence of predictor variables on all other cognitive domains.

      Conclusions

      While slowed processing speed appears to be the most core cognitive deficit in LLD, it was closely followed by executive function as a core cognitive deficit. Future research is needed to help clarify mechanisms leading to LLD- related changes in processing speed, including the potential role of white matter abnormalities.

      Key Words

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      References

        • Alexopoulos G.S.
        • Kiosses D.N.
        • Choi S.J.
        • Murphy C.F.
        • Lim K.O.
        Frontal white matter microstructure and treatment response of late-life depression.
        Am J Psychiatry. 2002; 159: 1929-1932
        • Alexopoulos G.S.
        • Meyers B.S.
        • Young R.C.
        • Campbell S.
        • Silbersweig D.
        • Charlson M.
        ‘Vascular depression’ hypothesis.
        Arch Gen Psychiatry. 1997; 54: 915-922
        • Alexopoulos G.S.
        • Meyers B.S.
        • Young R.C.
        • Kalayam B.
        • Kakuma T.
        • Gabrielle M.
        • et al.
        Executive dysfunction and long-term outcomes of geriatric depression.
        Arch Gen Psychiatry. 2000; 57: 285-290
        • Beats B.C.
        • Sahakian B.J.
        • Levy R.
        Cognitive performance in tests sensitive to frontal lobe dysfunction in the elderly depressed.
        Psychol Med. 1996; 26: 591-603
        • Boone K.B.
        • Lesser I.M.
        • Miller B.L.
        • Wohl M.
        • Berman N.
        • Lee A.
        • Palmer B.
        Cognitive functioning in a mildly to moderately depressed geriatric sample.
        J Neuropsychiatry Clin Neurosci. 1994; 6: 267-272
        • Boone K.B.
        • Lesser I.M.
        • Miller B.L.
        • Wohl M.
        • Berman N.
        • Lee A.
        • et al.
        Cognitive functioning in older depressed outpatients.
        Neuropsychology. 1995; 9: 390-398
        • Brodaty H.
        • Luscombe G.
        • Parker G.
        • Wilhelm K.
        • Hickie I.
        • Austin M.P.
        • Mitchell P.
        Early and late onset depression in old age.
        J Affect Disord. 2001; 66: 225-236
        • Butters M.A.
        • Whyte E.M.
        • Nebes R.D.
        • Begley A.E.
        • Dew M.A.
        • Mulsant B.H.
        • et al.
        The nature and determinants of neuropsychological functioning in late-life depression.
        Arch Gen Psychiatry. 2004; 61: 587-595
        • Caine E.D.
        • Lyness J.M.
        • King D.A.
        Reconsidering depression in the elderly.
        Am J Geriatr Psychiatry. 1993; 1: 4-20
        • Charney D.S.
        • Reynolds C.F.
        • Lewis L.
        • Lebowitz B.D.
        • Sunderland T.
        • Alexopoulos G.S.
        • 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; 60: 664-672
        • Coffey C.E.
        • Figiel G.S.
        • Djang W.T.
        • Weiner R.D.
        Subcortical hyperintensity on magnetic imaging.
        Am J Psychiatry. 1990; 147: 187-189
        • Degl’Innocenti A.
        • Agren H.
        • Backman L.
        Executive deficits in major depression.
        Acta Psychiatr Scand. 1998; 97: 182-188
        • Doraiswamy P.M.
        • Krishnan K.R.
        • Oxman T.
        • Jenkyn L.R.
        • Coffey D.
        • Burt T.
        • Clary C.M.
        Does antidepressant therapy improve cognition in elderly depressed patients?.
        J Geront. 2003; 58A: 1137-1144
        • Figiel G.S.
        • Krishnan K.R.
        • Doraiswamy P.M.
        • Rao V.P.
        • Nemeroff C.B.
        • Boyko O.B.
        Subcortical hyperintensities on brain Magnetic Resonance Imaging.
        Neurobiol Aging. 1991; 26: 245-247
        • Folstein M.F.
        • Robins L.N.
        • Helzer J.E.
        The Mini-Mental State Examination.
        Arch Gen Psychiatry. 1983; 40: 812
        • Fujikawa T.
        • Yamawaki S.
        • Touhouda Y.
        Incidence of silent cerebral infarction in patients with major depression.
        Stroke. 1993; 24: 1631-1634
        • Greenwald B.S.
        • Kramer-Ginsberg E.
        Age at onset in geriatric depression.
        J Affect Disord. 1988; 15: 61-68
        • Gupta S.R.
        • Naheedy M.H.
        • Young J.C.
        • Ghobrial M.
        • Rubino F.A.
        • Hindo W.
        Periventricular white matter changes and dementia. Clinical neuropsychological, radiological and pathological correlation.
        Arch Neurol. 1988; 45: 637-641
        • Hart R.P.
        • Kwentus J.A.
        • Taylor J.R.
        • Harkins S.W.
        Rate of forgetting in dementia and depression.
        J Consult Clin Psychol. 1987; 55: 101-105
        • Henry J.
        • Crawford J.R.
        A meta-analytic review of verbal fluency deficits in depression.
        J Clin Exp Neuropsychol. 2005; 27: 78-101
        • Kane M.J.
        • Engle R.W.
        The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence.
        Psychonomic Bull Rev. 2002; 9: 637-671
        • King D.A.
        • Caine E.D.
        • Conwell Y.
        • Cox C.
        The neuropsychology of depression in the elderly.
        J Neuropsychiatry Clin Neurosci. 1991; 3: 163-168
        • King D.A.
        • Caine E.D.
        • Cox C.
        Influence of depression and age on selected cognitive functions.
        Clin Neuropsychol. 1993; 7: 443-453
        • King D.A.
        • Cox C.
        • Lyness J.M.
        • Caine E.D.
        Neuropsychological effects of depression and age in an elderly sample.
        Neuropsychology. 1995; 9: 399-408
        • Kramer-Ginsberg E.
        • Greenwald B.S.
        • Krishnan K.R.
        • Christiansen B.
        • Hu B.
        • Ashtari M.
        • et al.
        Neuropsychological functioning and MRI signal hyperintensities in geriatric depression.
        Am J Psychiatry. 1999; 156: 438-444
        • Krishnan K.R.
        • Goli V.
        • Ellinwood E.H.
        • France R.D.
        • Blazer D.G.
        • Nemeroff C.B.
        Leukoencephalopathy in patients diagnosed as major depressive.
        Biol Psychiatry. 1988; 23: 519-522
        • La Rue A.
        • Goodman S.
        • Spar J.E.
        Risk factors for memory impairment in geriatric depression.
        Neuropsychiatry Neuropsychol Behav Neurol. 1992; 5: 178-184
        • Lebowitz B.D.
        • Pearson J.L.
        • Schneider L.S.
        • Reynolds C.F.
        • Alexopoulos G.S.
        • Bruce M.L.
        • et al.
        Diagnosis and treatment of depression in late life. Consensus statement update.
        JAMA. 1997; 278: 1186-1190
        • Lichtenberg P.A.
        • Ross T.
        • Millis S.R.
        • Manning C.A.
        The relationship between depression and cognition in older adults.
        J Gerontol B Psych Sci Soc Sci. 1995; 50: P25-P32
        • Lockwood K.A.
        • Alexopoulos G.S.
        • van Gorp W.G.
        Executive dysfunction in geriatric depression.
        Am J Psychiatry. 2002; 159: 1119-1126
        • Lyness J.M.
        • Caine E.D.
        • Cox C.
        • King D.A.
        • Conwell Y.
        • Olivares T.
        Cerebrovascular risk factors and later-life major depression. Testing a small-vessel brain disease model.
        Am J Geriatr Psychiatry. 1998; 6: 5-13
        • Lyness S.A.
        • Eaton Em
        • Schneider L.S.
        Cognitive performance in older and middle-aged depressed outpatients and controls.
        J Gerontol B Psych Sci Soc Sci. 1994; 49: P129-P136
        • Mehta K.M.
        • Simonsick E.M.
        • Rooks R.
        • Newman A.B.
        • Pope S.K.
        • Rubin S.M.
        • et al.
        Black and white differences in cognitive function test scores.
        J Am Geriatr Sco. 2004; 52: 2120-2127
        • Meng X.
        • Rosenthal R.
        • Rubin D.B.
        Comparing correlated correlation coefficients.
        Psychological Bulletin. 1992; 111: 172-175
        • Miller M.D.
        • Paradis C.F.
        • Houck P.R.
        • Mazumdar S.
        • Stack J.A.
        • Rifai A.H.
        • et al.
        Rating chronic medical illness burden in geropsychiatric practice and research.
        Psychiatry Res. 1992; 41: 237-248
        • Nebes R.D.
        • Butters M.A.
        • Mulsant B.H.
        • Pollock B.G.
        • Zmuda M.
        • Houck P.R.
        • Reynolds C.F.
        Decreased working memory and processing speed mediate cognitive impairment in geriatric depression.
        Psychol Med. 2000; 30: 679-691
        • Rapp M.A.
        • Dahlman K.
        • Sano M.
        • Grossman H.T.
        • Haroutunian V.
        • Gorman J.M.
        Neuropsychological differences between late-onset and recurrent geriatric major depression.
        Am J Psychiatry. 2005; 162: 691-698
        • Raskin A.
        Partialing out the effects of depression and age on cognitive functions.
        in: Poon L.W. Handbook for Clinical Memory Assessment of Older Adults. American Psychological Association, Washington, DC1986: 244-256
        • Salloway S.
        • Malloy P.
        • Kohn R.
        • Gillard E.
        • Duffy J.
        • Rogg J.
        • et al.
        MRI and neuropsychological deficits in early- and late-life-onset geriatric depression.
        Neurology. 1996; 46: 1567-1574
        • Salthouse T.A.
        Aging and measures of processing speed.
        Biol Psychology. 2000; 54: 35-40
        • Steingart A.
        • Hermann N.
        Major depressive disorder in the elderly.
        Int J Geriatr Psychiatry. 1991; 6: 593-598
        • Taylor W.D.
        • MacFall J.R.
        • Payne M.E.
        • McQuoid D.R.
        • Provenzale J.M.
        • Steffens D.C.
        • Krishnan K.R.
        Late-life depression and microstructural abnormalities in dorsolateral prefrontal cortex white matter.
        Am J Psychiatry. 2004; 161: 1293-1296
        • van Ojen R.
        • Hooijer C.
        • Bezemer D.
        • Jonker C.
        • Lindelboom J.
        • van Tilburg W.
        Late-life depressive disorder in the community, I.
        Br J Psychiatry. 1995; 156: 311-315
        • van Reekum R.
        • Simard M.
        • Clarke D.
        • Binns M.A.
        • Conn D.
        Late-life depression as a possible predictor of dementia.
        Am J Geriatr Psychiatry. 1999; 7: 151-159
        • Waldstein S.R.
        • Katzel L.I.
        Gender differences in the relation of hypertension to cognitive function in older adults.
        Neurol Res. 2004; 26: 502-506
        • Wolf P.A.
        • D’Agostino R.B.
        • Belanger A.J.
        • Kannel W.B.
        Probability of stroke.
        Stroke. 1991; 22: 312-318
        • Ylikoski R.
        • Ylikoski A.
        • Raininko R.
        • Keskivaara P.
        • Sulkava R.
        • Tilvis R.
        • Erkinjuntti T.
        Cardiovascular diseases, health status, brain imaging findings and neuropsychological functioning in neurologically healthy elderly individuals.
        Arch Gerontol Geriatr. 2000; 30: 115-130