Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer’s disease (AD), with control of vascular factors (VFs). Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES) study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (nD), past depression (pD), present depression (prD), and present and past depression (prpD). Logistic regression was used. Results. Data of 1,807 subjects were investigated at baseline (mean age 74.3, 59.3% women), and 1,376 (81.6%) subjects were evaluated after three years. The prevalence of dementia at baseline was 6.7%, and dementia incidence was 6.3%. An effect of depression was observed on dementia prevalence (OR [CI 95%] 1.84 [1.01–3.35] for prD and 2.73 [1.08–6.87] for prpD), and on dementia due to AD (OR 1.98 [0.98–3.99] for prD and OR 3.98 [1.48–10.71] for prpD) (fully adjusted models, nD as reference). Depression did not influence dementia incidence. Conclusions. Present depression and, particularly, present and past depression are associated with dementia at old age. Multiple mechanisms, including toxic effect of depression on hippocampal neurons, plausibly explain these associations. 1. Introduction Depression has been associated with an increased risk of dementia in old age, but the mechanisms underlying this association are not well understood. Several hypothetical, not mutually exclusive, mechanisms can be proposed: (1) depression is a prodrome of dementia, (2) depression reduces the threshold for dementia manifestation, and (3) depression leads to damage to neural systems, particularly the hippocampus, thus contributing to the development of dementia [1]. In addition, depression can be regarded as a potential reaction to early cognitive deficits. In fact, one epidemiological study reported depressive symptoms following the onset of dementia, rather than preceding it [2]. Under any of the above-mentioned mechanisms, depression at any time during life should be associated with an increased risk of dementia in unselected old population. An important role of vascular factors (VFs) in the association between depression and dementia is also possible. Indeed, previous studies demonstrated that cerebrovascular disease (CVD), hypertension, diabetes, and other VFs may cause both cognitive impairment [3, 4] and depression [5]. Depression could also influence
References
[1]
A. F. Jorm, “History of depression as a risk factor for dementia: an updated review,” Australian and New Zealand Journal of Psychiatry, vol. 35, no. 6, pp. 776–781, 2001.
[2]
P. Chen, M. Ganguli, B. H. Mulsant, and S. T. DeKosky, “The temporal relationship between depressive symptoms and dementia: a community-based prospective study,” Archives of General Psychiatry, vol. 56, no. 3, pp. 261–266, 1999.
[3]
L. J. Launer, “Demonstrating the case that AD is a vascular disease: epidemiologic evidence,” Ageing Research Reviews, vol. 1, no. 1, pp. 61–77, 2002.
[4]
S. E. Vermeer, N. D. Prins, T. den Heijer, A. Hofman, P. J. Koudstaal, and M. M. B. Breteler, “Silent brain infarcts and the risk of dementia and cognitive decline,” The New England Journal of Medicine, vol. 348, no. 13, pp. 1215–1222, 2003.
[5]
G. S. Alexopoulos, “The vascular depression hypothesis: 10 years later,” Biological Psychiatry, vol. 60, no. 12, pp. 1304–1305, 2006.
[6]
E. Kitzlerová and M. Anders, “The role of some new factors in the pathophysiology of depression and cardiovascular disease: overview of recent research,” Neuroendocrinology Letters, vol. 28, no. 6, pp. 832–840, 2007.
[7]
D. E. Barnes, G. S. Alexopoulos, O. L. Lopez, J. D. Williamson, and K. Yaffe, “Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the cardiovascular health study,” Archives of General Psychiatry, vol. 63, no. 3, pp. 273–279, 2006.
[8]
F. Bermejo, R. Gabriel, S. Vega, J. M. Morales, W. A. Rocca, and D. W. Anderson, “Problems and issues with door-to-door, two-phase surveys: an illustration from central spain,” Neuroepidemiology, vol. 20, no. 4, pp. 225–231, 2001.
[9]
J. M. Morales, F. P. Bermejo, J. Benito-León et al., “Methods and demographic findings of the baseline survey of the NEDICES cohort: a door-to-door survey of neurological disorders in three communities from Central Spain,” Public Health, vol. 118, no. 6, pp. 426–433, 2004.
[10]
M. F. Folstein, S. E. Folstein, and P. R. McHugh, “Mini-mental state. A practical method for grading the cognitive state of patients for the clinician,” Journal of Psychiatric Research, vol. 12, no. 3, pp. 189–198, 1975.
[11]
R. I. Pfeffer, T. T. Kurosaki, C. H. Harrah Jr., J. M. Chance, and S. Filos, “Measurement of functional activities in older adults in the community,” Journals of Gerontology, vol. 37, no. 3, pp. 323–329, 1982.
[12]
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association, Washington, DC, USA, 4th edition, 1994.
[13]
G. McKhann, D. Drachman, M. Folstein, R. Katzman, D. Price, and E. M. Stadlan, “Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease,” Neurology, vol. 34, no. 7, pp. 939–944, 1984.
[14]
G. C. Román, T. K. Tatemichi, T. Erkinjuntti et al., “Vascular dementia: diagnostic criteria for research studies: report of the NINDS-AIREN international workshop,” Neurology, vol. 43, no. 2, pp. 250–260, 1993.
[15]
G. Li, L. Y. Wang, J. B. Shofer et al., “Temporal relationship between depression and dementia: findings from a large community-based 15-year follow-up study,” Archives of General Psychiatry, vol. 68, no. 9, pp. 970–977, 2011.
[16]
R. M. Sapolsky, “Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders,” Archives of General Psychiatry, vol. 57, no. 10, pp. 925–935, 2000.
[17]
V. M. Dotson, M. A. Beydoun, and A. B. Zonderman, “Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment,” Neurology, vol. 75, no. 1, pp. 27–34, 2010.
[18]
L. M. Tai, K. L. Youmans, L. Jungbauer, C. Yu, and M. J. LaDu, “Introducing human APOE into Aβ transgenic mouse models,” International Journal of Alzheimer's Disease, vol. 2011, Article ID 810981, 9 pages, 2011.
[19]
F. Irie, K. H. Masaki, H. Petrovitch et al., “Apolipoprotein E ε4 allele genotype and the effect of depressive symptoms on the risk of dementia in men: the Honolulu-Asia aging study,” Archives of General Psychiatry, vol. 65, no. 8, pp. 906–912, 2008.
[20]
A. D. Korczyn, “Why have we failed to cure Alzheimer's disease?” Journal of Alzheimer's Disease, vol. 29, no. 2, pp. 275–282, 2012.
[21]
D. A. Snowdon, S. J. Kemper, J. A. Mortimer, L. H. Greiner, D. R. Wekstein, and W. R. Markesbery, “Linguistic ability in early life and cognitive function and Alzheimer's disease in late life: findings from the Nun study,” Journal of the American Medical Association, vol. 275, no. 7, pp. 528–532, 1996.
[22]
L. J. Whalley, J. M. Starr, R. Athawes, D. Hunter, A. Pattie, and I. J. Deary, “Childhood mental ability and dementia,” Neurology, vol. 55, no. 10, pp. 1455–1459, 2000.
[23]
D. P. Devanand, M. Sano, M. X. Tang et al., “Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community,” Archives of General Psychiatry, vol. 53, no. 2, pp. 175–182, 1996.
[24]
R. Peters, E. Pinto, N. Beckett et al., “Association of depression with subsequent mortality, cardiovascular morbidity and incident dementia in people aged 80 and over and suffering from hypertension. Data from the hypertension in the very elderly trial (HYVET),” Age and Ageing, vol. 39, no. 4, Article ID afq042, pp. 439–445, 2010.
[25]
J. S. Saczynski, A. Beiser, S. Seshadri, S. Auerbach, P. A. Wolf, and R. Au, “Depressive symptoms and risk of dementia: the framingham heart study,” Neurology, vol. 75, no. 1, pp. 35–41, 2010.
[26]
J. T. Becker, Y. Chang, O. L. Lopez et al., “Depressed mood is not a risk factor for incident dementia in a community-based cohort,” The American Journal of Geriatric Psychiatry, vol. 17, no. 8, pp. 653–663, 2009.
[27]
B. V. Chilovi, M. Conti, M. Zanetti, I. Mazzù, L. Rozzini, and A. Padovani, “Differential impact of apathy and depression in the development of dementia in mild cognitive impairment patients,” Dementia and Geriatric Cognitive Disorders, vol. 27, no. 4, pp. 390–398, 2009.
