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BDNF serum levels are not related to cognitive functioning in older depressed patients and controls

  • Annemiek Dols (a1), Carisha S. Thesing (a1), Filip Bouckaert (a2), Richard C. Oude Voshaar (a3), Hannie C. Comijs (a1) and M. L. Stek (a1)...



Depression and cognitive decline are highly prevalent in older persons and both are associated with low serum brain derived neurotrophic factor (BDNF). Mutual pathways of depression and cognitive decline in older persons may explain the overlap in symptoms and low serum BDNF. We hypothesized that serum BDNF levels are lower in depressed elderly with poor cognitive performance (global or specifically in working memory, speed of information processing, and episodic memory) compared to depressed elderly without cognitive impairment or non-depressed controls.


BDNF Serum levels and cognitive functioning were examined in 378 depressed persons and 132 non-depressed controls from a large prospective study on late-life depression. The association between BDNF levels and each cognitive domain among the depressed patients was tested by four separate linear regression models adjusted for relevant covariates. An analysis of covariance (ANCOVA) was performed to compare BDNF serum levels in three groups (depression with cognitive impairment, depression without cognitive impairment, and non-depressed controls), when adjusted for potential confounders.


No significant linear association was found between BDNF and any of the four cognitive domains tested. There are no differences in BDNF levels between controls and depressed patients with or without cognitive impairment global or in specific domains after controlling for confounders.


BDNF serum levels in this cohort of older depressed patients and controls are not related to cognitive functioning. As BDNF is essential for the survival and functioning of neurons, its levels may remain normal in stages of disease where remission is achievable.


Corresponding author

Correspondence should be addressed to: A. Dols, De Nieuwe Valeriuskliniek GGZ inGeest, Amstelveenseweg 589, 1070 BB Amsterdam, the Netherlands. Phone: +31-20-7885-565; Fax: +31-20-7885-577. Email:


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APA (2000). Diagnostic and Statistical Manual of Mental Disorders, Washington, DC: American Psychiatric Press.
Bhalla, R. K. et al. (2006). Persistence of neuropsychologic deficits in the remitted state of late-life depression. American Journal of Geriatric Psychiatry, 14, 419427.
Bus, B. A. et al. (2011). Serum brain-derived neurotrophic factor: determinants and relationship with depressive symptoms in a community population of middle-aged and elderly people. The World Journal of Biological Psychiatry, 13, 3947.
Butters, M. A. et al. (2000). Changes in cognitive functioning following treatment of late-life depression. American Journal of Psychiatry, 157, 19491954.
Craig, C. L. et al. (2003). International physical activity questionnaire: 12-country reliability and validity. Medicine and Science in Sports and Exercise, 35, 13811395.
Comijs, H. C. et al. (2011). The Netherlands study of depression in older persons (NESDO); a prospective cohort study. BMC Research Notes, 4, 524.
Diniz, B. S. et al. (2013). Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study. Journal of Psychiatric Research, 49, 96101.
Driscoll, I. (2012). Plasma BDNF is associated with age-related white matter atrophy but not with cognitive function in older, non-demented adults. PLoS One, 7, e35217.
Erickson, K. I. et al. (2010). Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume. Journal of Neuroscience, 30, 53685375.
Folstein, M. F., Folstein, S. E. and Mchugh, P. R. (1975). Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.
Jolliffe, I. T. (1972). Discarding variables in a principal component analysis, I: artificial data. Journal of the Royal Statistical Society, Series C (Applied Statistics), 21, 160173.
Kapczinski, F. et al. (2010). Peripheral biomarkers and illness activity in bipolar disorder. Journal of Psychiatric Research, 45, 156161.
Klein, M., Ponds, R. W., Houx, P. J. and Jolles, J. (1997). Effect of test duration on age-related differences in stroop interference. Journal of Clinical and Experimental Neuropsychology, 19, 7782.
Korten, N. C. et al. (2014). Heterogeneity of late-life depression: relationship with cognitive functioning. International Psychogeriatrics, 26, 953963.
Kriegsman, D. M., Penninx, B. W., Van Eijk, J. T., Boeke, A. J. and Deeg, D. J. (1996). Self-reports and general practitioner information on the presence of chronic diseases in community dwelling elderly. A study on the accuracy of patients’ self-reports and on determinants of inaccuracy. Journal of Clinical Epidemiology, 49, 14071417.
Laske, C. et al. (2010). Higher BDNF serum levels predict slower cognitive decline in Alzheimer's disease patients. The International Journal of Neuropsychopharmacology, 14, 399404.
Laske, C. et al. (2006). Stage-dependent BDNF serum concentrations in Alzheimer's disease. Journal of Neural Transmission, 113, 12171224.
Molendijk, M. L. et al. (2010). Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment. Molecular Psychiatry, 16, 10881095.
Molendijk, M. L., Spinhoven, P., Polak, M., Bus, B. A., Penninx, B. W. and Elzinga, B. M. (2014). Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N = 9484). Molecular Psychiatry, 19, 791800.
Nettiksimmons, J., Simonsick, E. M., Harris, T., Satterfield, S., Rosano, C. and Yaffe, K. (2014). The associations between serum brain-derived neurotrophic factor, potential confounders, and cognitive decline: a longitudinal study. PLoS One, 9, e91339.
Oral, E., Canpolat, S., Yildirim, S., Gulec, M., Aliyev, E. and Aydin, N. (2012). Cognitive functions and serum levels of brain-derived neurotrophic factor in patients with major depressive disorder. Brain Research Bulletin, 88, 454459.
Peng, S., Wuu, J., Mufson, E. J. and Fahnestock, M. (2005). Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. Journal of Neurochemistry, 93, 14121421.
Rey, A. (1964). L’examen Clinique en Psychologie. France, Paris: Presses Universitaire de France.
Rush, A. J., Gullion, C. M., Basco, M. R., Jarrett, R. B. and Trivedi, M. H. (1996). The inventory of depressive symptomatology (IDS): psychometric properties. Psychological Medicine, 26, 477486.
Saunders, J. B., Aasland, O. G., Babor, T. F., de la Fuente, J. R. and Grant, M. (1993). Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption–II. Addiction, 88, 791804.
Sen, S., Duman, R. and Sanacora, G. (2008). Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biological Psychiatry, 64, 527532.
Shimada, H. et al. (2014). A large, cross-sectional observational study of serum BDNF, cognitive function, and mild cognitive impairment in the elderly. Frontiers in Aging Neuroscience, 6, 69.
Stroop, J. (1935). Studies of interference in serial verbal reactions. Journal of Experimental Psychology, 18, 643662.
Van der Meij, A., Comijs, H. C., Dols, A., Janzing, J. G. and Oude Voshaar, R. C. (2014). BDNF in late-life depression: Effect of SSRI usage and interaction with childhood abuse. Psychoneuroendocrinology, 43, 8189.
Wechsler, D. (1958). The Measurement and Appraisal of Adult Intelligence. Baltimore, Williams & Wilkins.
Weinstein, G. et al. (2014). Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study. JAMA Neurology, 71, 5561.
Wittchen, H. U., Robins, L. N., Cottler, L. B., Sartorius, N., Burke, J. D. and Regier, D. (1991). Cross-cultural feasibility, reliability and sources of variance of the Composite International Diagnostic Interview (CIDI). The multicentre WHO/ADAMHA field trials. British Journal of Psychiatry, 159, 645653, 658.
Ziegenhorn, A. A. et al. (2007). Serum neurotrophins–a study on the time course and influencing factors in a large old age sample. Neurobiology of Aging, 28, 14361445.


BDNF serum levels are not related to cognitive functioning in older depressed patients and controls

  • Annemiek Dols (a1), Carisha S. Thesing (a1), Filip Bouckaert (a2), Richard C. Oude Voshaar (a3), Hannie C. Comijs (a1) and M. L. Stek (a1)...


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