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Latent Classes of Cognitive Functioning Among Depressed Older Adults Without Dementia

  • Ruth T. Morin (a1), Philip Insel (a2) (a3), Craig Nelson (a4), Meryl Butters (a5), David Bickford (a4), Susan Landau (a6), Andrew Saykin (a7), Michael Weiner (a4), R. Scott Mackin (a1) (a2) (a4) and the ADNI Depression Project (a1) (a2) (a3) (a4) (a5) (a6) (a7)...

Abstract

Objective:

Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership.

Method:

Neuropsychological assessment data from 121 participants in the Alzheimer’s Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed.

Results:

A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership.

Conclusion:

LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.

Copyright

Corresponding author

*Correspondence and reprint requests to: Ruth T. Morin, San Francisco VA Medical Center, 4150 Clement Street, Mental Health Service, San Francisco, CA 94121. E-mail: ruth.morin@va.gov; (415) 221-4810 x23114.

References

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Aisen, P.S., Petersen, R.C., Donohue, M.C., Gamst, A., Raman, R., Thomas, R.G., … Weiner, M.W. (2010). Clinical core of the Alzheimer’s disease neuroimaging initiative: Progress and plans. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 6(3), 239246. doi: 10.1016/j.jalz.2010.03.006
Ballard, C., Bannister, C., Solis, M., Oyebode, F., & Wilcock, G. (1996). The prevalence, associations and symptoms of depression amongst dementia sufferers. Journal of Affective Disorders, 36(3), 135144.
Ballmaier, M., Narr, K.L., Toga, A.W., Elderkin-Thompson, V., Thompson, P.M., Hamilton, L., … Kumar, A. (2008). Hippocampal morphology and distinguishing late-onset from early-onset elderly depression. American Journal of Psychiatry, 165(2), 229237.
Benedict, R.H. (1997). Brief visuospatial memory test–revised: professional manual. PAR.
Benton, A.L. (1983). Judgment of line orientation. Oxford: Oxford University Press.
Blazer, D.G. (2003). Depression in Late Life: Review and Commentary. The Journals of Gerontology: Series A, 58(3), M249M265. doi: 10.1093/gerona/58.3.M249
Brandt, J. (1991). The Hopkins Verbal Learning Test: Development of a new memory test with six equivalent forms. The Clinical Neuropsychologist, 5(2), 125142.
Brodrick, J.E., & Mathys, M.L. (2016). Antidepressant Exposure and Risk of Dementia in Older Adults with Major Depressive Disorder. Journal of the American Geriatrics Society, 64(12), 25172521.
Bruce, M.L. (2001). Depression and Disability in Late Life: Directions for Future Research. The American Journal of geriatric psychiatry, 9(2), 102112. doi: 10.1097/00019442-200105000-00003
Butters, M.A., Whyte, E.M., Nebes, R.D., Begley, A.E., Dew, M.A., Mulsant, B.H., … Pollock, B.G. (2004). The nature and determinants of neuropsychological functioning in late-lifedepression. Archives of General Psychiatry, 61(6), 587595.
Byers, A.L., & Yaffe, K. (2011). Depression and risk of developing dementia. Nature Reviews Neurology, 7(6), 323331.
Carrière, I., Norton, J., Farré, A., Wyart, M., Tzourio, C., Noize, P.,… Ancelin, M.L. (2017). Antidepressant use and cognitive decline in community-dwelling elderly people–The Three-City Cohort. BMC medicine, 15(1), 81.
Caselli, R.J., Beach, T.G., Knopman, D.S., & Graff-Radford, N.R. (2017). Alzheimer Disease: Scientific Breakthroughs and Translational Challenges. Mayo Clinic Proceedings, 92(6), 978994. doi: 10.1016/j.mayocp.2017.02.011
Cohen, J. (1990). Things I have learned (so far). American psychologist, 45(12), 1304.
Colarusso, R.P., & Hammill, D.D. (1972). Motor-free visual perception test: Academic Therapy Pub.
Corsentino, E.A., Sawyer, K., Sachs-Ericsson, N., & Blazer, D.G. (2009). Depressive symptoms moderate the influence of the apolipoproteinE ϵ4 allele on cognitive decline in a sample of community dwelling older adults. The American Journal of geriatric psychiatry, 17(2), 155165.
Direk, N., Schrijvers, E.M., de Bruijn, R.F., Mirza, S., Hofman, A., Ikram, M.A., & Tiemeier, H. (2013). Plasma amyloid β, depression, and dementia in community-dwelling elderly. Journal of psychiatric research, 47(4), 479485.
Doraiswamy, P.M., Krishnan, K.R.R., Oxman, T., Jenkyn, L.R., Coffey, D.J., Burt, T., & Clary, C.M. (2003). Does antidepressant therapy improve cognition in elderly depressed patients?. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 58(12), M1137M1144.
Dotson, V.M., Beydoun, M.A., & Zonderman, A.B. (2010). Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment. Neurology, 75(1), 2734.
Frances, A. (1994). Diagnostic and statistical manual of mental disorders: DSM-IV: American Psychiatric Association.
Gabryelewicz, T., Styczynska, M., Luczywek, E., Barczak, A., Pfeffer, A., Androsiuk, W., … Barcikowska, M. (2007). The rate of conversion of mild cognitive impairment to dementia: predictive role of depression. International journal of geriatric psychiatry, 22(6), 563567. doi: 10.1002/gps.1716
Geda, Y.E., Knopman, D.S., Mrazek, D.A., Jicha, G.A., Smith, G.., Negash, S., … Pankratz, V.S. (2006). Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Archives of neurology, 63(3), 435440.
Geerlings, M., den Heijer, T., Koudstaal, P.J., Hofman, A., & Breteler, M. (2008). History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease. Neurology, 70(15), 12581264.
Genin, E., Hannequin, D., Wallon, D., Sleegers, K., Hiltunen, M., Combarros, O., … Berr, C. (2011). APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Molecular psychiatry, 16(9), 903907.
Golden, C., & Freshwater, S. (2002). Stroop Color and Word Test, Revised 2002 Adult Manual for Clinical and Experimental Uses. Wood Dale, IL: Stoelting.
Hamilton, M. (1960). A rating scale for depression. Journal of neurology, neurosurgery, and psychiatry, 23(1), 56.
Harrington, K.D., Gould, E., Lim, Y.Y., Ames, D., Pietrzak, R.H., Rembach, A., … Villemagne, V.L. (2017). Amyloid burden and incident depressive symptoms in cognitively normal older adults. International journal of geriatric psychiatry, 32(4), 455463.
Harrington, K.D., Lim, Y.Y., Gould, E., & Maruff, P. (2015). Amyloid-beta and depression in healthy older adults: a systematic review. Australian & New Zealand Journal of Psychiatry, 49(1), 3646.
Jansen, W.J., Ossenkoppele, R., Knol, D.L., Tijms, B.M., Scheltens, P., Verhey, F.R., … Alcolea, D. (2015). Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA, 313(19), 19241938.
Janssen, J., Pol, H.E.H., de Leeuw, F.-E., Schnack, H.G., Lampe, I.K., Kok, R.M., … Heeren, T.J. (2007). Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression. Journal of Neurology, Neurosurgery & Psychiatry, 78(6), 638640.
Jones, H.E., Joshi, A., Shenkin, S., & Mead, G.E. (2016). The effect of treatment with selective serotonin reuptake inhibitors in comparison to placebo in the progression of dementia: a systematic review and meta-analysis. Age and ageing, 45(4), 448456.
Jung, T., & Wickrama, K. (2008). An introduction to latent class growth analysis and growth mixture modeling. Social and personality psychology compass, 2(1), 302317.
Kaplan, E., Goodglass, H., & Weintraub, S. (1983). The Boston naming test. 2nd. Philadelphia: Lea & Febiger.
Kessler, R.C., Birnbaum, H., Bromet, E., Hwang, I., Sampson, N., & Shahly, V. (2010). Age Differences in Major depression: Results from the National Comorbidity Surveys Replication (NCS-R). Psychological medicine, 40(2), 225. doi: 10.1017/S0033291709990213
Koenig, A.M., Bhalla, R.K., & Butters, M.A. (2014). Cognitive Functioning and Late-Life Depression. Journal of the International Neuropsychological Society, 20(5), 461467. doi: 10.1017/S1355617714000198
Koyama, A., Okereke, O.I., Yang, T., Blacker, D., Selkoe, D.J., & Grodstein, F. (2012). Plasma amyloid-β as a predictor of dementia and cognitive decline: a systematic review and meta-analysis. Archives of neurology, 69(7), 824831.
Landau, S.M., Mintun, M.A., Joshi, A.D., Koeppe, R.A., Petersen, R.C., Aisen, P.S., … Jagust, W.J. (2012). Amyloid Deposition, Hypometabolism, and Longitudinal Cognitive Decline. Annals of neurology, 72(4), 578586. doi: 10.1002/ana.23650
Lee, C., Lin, C.-L., Sung, F.-C., Liang, J.-A., & Kao, C.-H. (2016). Antidepressant treatment and risk of dementia: a population-based, retrospective case-control study. The Journal of clinical psychiatry, 77(1), 117122; quiz 122.
Lockwood, K.A., Alexopoulos, G.S., Kakuma, T., & Van Gorp, W.G. (2000). Subtypes of Cognitive Impairment in Depressed Older Adults. The American Journal of geriatric psychiatry, 8(3), 201208. doi: 10.1097/00019442-200008000-00004
Mackin, R.S., Nelson, J.C., Delucchi, K.L., Raue, P.J., Satre, D.D., Kiosses, D.N., … Arean, P.A. (2014). Association of age at depression onset with cognitive functioning in individuals with late-life depression and executive dysfunction. The American Journal of geriatric psychiatry, 22(12), 16331641.
Meng, X., & D’Arcy, C. (2012). Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses. PLOS ONE, 7(6), e38268.
Murray, C.J., Lopez, A.D., & Organization, W.H. (1996). The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020: summary.
Muthén, L.K., & Muthén, B.O. (2007). Mplus. Statistical analysis with latent variables. Version, 3.
Nie, N., Hull, C., & Bent, D. (2011). IBM statistical package for the social sciences (SPSS Version 20). Computer Software. Chicago, IL: SPSS.
Nylund, K.L., Asparouhov, T., & Muthén, B.O. (2007). Deciding on the number of classes in latent class analysis and growth mixture modeling: A Monte Carlo simulation study. Structural equation modeling, 14(4), 535569.
Regier, D.A., Boyd, J.H., Burke, J.D., Rae, D.S., Myers, J.K., Kramer, M., … Locke, B.Z. (1988). One-month prevalence of mental disorders in the United States: Based on five epidemiologic catchment area sites. Archives of General Psychiatry, 45(11), 977986.
Reitan, R., & Wolfson, D. (1993). The Halstead-Reitan Neuropsychological Battery. Theory and clinical interpretation Neuropsychology Press, Tuscan, AZ.
Rey, A. (1964). L’examen clinique en psychologie [The clinical psychological examination]. Paris: Presses Universitaires de France.
Riddle, M., Potter, G.G., McQuoid, D.R., Steffens, D.C., Beyer, J.L., & Taylor, W.D. (2017). Longitudinal cognitive outcomes of clinical phenotypes of late-life depression. The American Journal of geriatric psychiatry, 25(10), 11231134.
Rusmaully, J., Dugravot, A., Moatti, J.-P., Marmot, M.G., Elbaz, A., Kivimaki, M., … Singh-Manoux, A. (2017). Contribution of cognitive performance and cognitive decline to associations between socioeconomic factors and dementia: A cohort study. PLoS medicine, 14(6), e1002334.
Savitz, J., Solms, M., & Ramesar, R. (2006). Apolipoprotein E variants and cognition in healthy individuals: A critical opinion. Brain Research Reviews, 51(1), 125135. doi: 10.1016/j.brainresrev.2005.10.006
Sheline, Y.I., Gado, M.H., & Kraemer, H.C. (2003). Untreated depression and hippocampal volume loss. American Journal of Psychiatry, 160(8), 15161518.
Sneed, J.R., Rindskopf, D., Steffens, D.C., Krishnan, K.R.R., & Roose, S.P. (2008). The vascular depression subtype: evidence of internal validity. Biological psychiatry, 64(6), 491497.
Steffens, . (2017). Late-life depression and the prodromes of dementia. JAMA Psychiatry, 74(7), 673674.
Steffens, , McQuoid, D.R., Payne, M.E., & Potter, G.G.(2011). Change in hippocampal volume on magnetic resonance imaging and cognitive decline among older depressed and nondepressed subjects in the neurocognitive outcomes of depression in the elderly study. The American Journal of geriatric psychiatry, 19(1), 412.
Sun, X., Steffens, D.C., Au, R., Folstein, M., Summergrad, P., Yee, J., … Qiu, W.Q. (2008). Amyloid-associated depression: a prodromal depression of Alzheimer disease?. Archives of General Psychiatry, 65(5), 542550.
Uher, R., Perlis, R.H., Placentino, A., Dernovšek, M.Z., Henigsberg, N., Mors, O., … Farmer, A. (2012). Self‐report and clinician‐rated measures of depression severity: can one replace the other?. Depression and Anxiety, 29(12), 10431049.
Wechsler, D. (1987). Wechsler memory scale-revised (WMS-R): Psychological Corporation.
Wechsler, D. (1997). Adult intelligence scale. New York, 21.
Wu, K.-Y., Hsiao, T., Chen, C.-S., Chen, C.-H., Hsieh, C.-J., Wai, Y.-Y., … Liu, C.-Y. (2014). Increased brain amyloid deposition in patients with a lifetime history of major depression: evidenced on 18F-florbetapir (AV-45/Amyvid) positron emission tomography. European journal of nuclear medicine and molecular imaging, 41(4), 714722.
Yen, Y.-C., Rebok, G.W., Gallo, J.J., Yang, M.-J., Lung, F.-W., & Shih, C.-H. (2007). ApoE4 allele is associated with late-life depression: a population-based study. The American Journal of geriatric psychiatry, 15(10), 858868.

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