This study examined whether there were neuroanatomical differences evident on CT scans of individuals with dementia who differed on depression history. Neuroanatomical variables consisted of visual ratings of frontal lobe deep white matter, subcortical white matter, and subcortical gray matter hypodensities in the CT scans of 182 individuals from the Study of Dementia in Swedish Twins who were diagnosed with dementia and had information on depression history. Compared to individuals with Alzheimer's disease and no depression, individuals with Alzheimer's disease and late-onset depression (first depressive episode at age 60 or over) had a greater number of striatal hypodensities (gray matter hypodensities in the caudate nucleus and lentiform nucleus). There were no significant differences in frontal lobe deep white matter or subcortical white matter. These findings suggest that late-onset depression may be a process that is distinct from the neurodegenerative changes caused by Alzheimer's disease. 1. Introduction While some studies have suggested that a history of depression is a risk factor for dementia later in life (e.g., [1, 2]), a number of authors have concluded that depression is an early symptom of dementia [3–6]. Boland [7] proposed that prodromal depression arises from dementia-related neuropathology. Several studies of nondemented older adults have suggested an association between white matter lesions and depression, specifically late-onset depression [8–14]. In a longitudinal study, white matter changes pre-dated and independently predicted the onset of depressive symptoms in older adult participants [15], providing some evidence that white matter changes are an antecedent to depression. Furthermore, in their review, Schweitzer et al. [16] concluded that the white matter changes that are common in individuals with late-onset depression were associated with cognitive impairment, and thus, were indicative of a prodrome to dementia. A greater amount of total brain white matter lesions has been associated with more severe depression or a greater number of depressive symptoms [9, 17, 18]. Other studies have suggested that white matter lesions in the frontal lobe are specifically associated with a higher rate of depressive symptoms among persons without dementia [8, 19]. A review of white matter lesions and clinical manifestations concluded that while periventricular white matter lesions are often associated with Alzheimer’s disease (AD), lesions in the subcortical white matter are more often associated with late-onset depression [16]. Among 39
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]
R. S. Wilson, G. M. Hoganson, K. B. Rajan, L. L. Barnes, C. F. Mendes De Leon, and D. A. Evans, “Temporal course of depressive symptoms during the development of Alzheimer disease,” Neurology, vol. 75, no. 1, pp. 21–26, 2010.
[3]
J. A. Brommelhoff, M. Gatz, B. Johansson, J. J. McArdle, L. Fratiglioni, and N. L. Pedersen, “Depression as a risk factor or prodromal feature for dementia? findings in a population-based sample of Swedish Twins,” Psychology and Aging, vol. 24, no. 2, pp. 373–384, 2009.
[4]
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.
[5]
J. L. Wetherell, M. Gatz, B. Johansson, and N. L. Pedersen, “History of depression and other psychiatric illness as risk factors for Alzheimer disease in a twin sample,” Alzheimer Disease and Associated Disorders, vol. 13, no. 1, pp. 47–52, 1999.
[6]
K. Yaffe, T. Blackwell, R. Gore, L. Sands, V. Reus, and W. S. Browner, “Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study,” Archives of General Psychiatry, vol. 56, no. 5, pp. 425–430, 1999.
[7]
R. J. Boland, “Depression in Alzheimer's disease and other dementias,” Current Psychiatry Reports, vol. 2, no. 5, pp. 427–433, 2000.
[8]
M. J. Firbank, J. T. O'Brien, S. Pakrasi et al., “White matter hyperintensities and depression—Preliminary results from the LADIS study,” International Journal of Geriatric Psychiatry, vol. 20, no. 7, pp. 674–679, 2005.
[9]
A. F. Jorm, K. J. Anstey, H. Christensen et al., “MRI hyperintensities and depressive symptoms in a community sample of individuals 60-64 years old,” American Journal of Psychiatry, vol. 162, no. 4, pp. 699–704, 2005.
[10]
M. S. Krishnan, J. T. O'Brien, M. J. Firbank et al., “Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study,” International Journal of Geriatric Psychiatry, vol. 21, no. 10, pp. 983–989, 2006.
[11]
I. M. Lesser, K. B. Boone, C. M. Mehringer, M. A. Wohl, B. L. Miller, and N. G. Berman, “Cognition and white matter hyperintensities in older depressed patients,” American Journal of Psychiatry, vol. 153, no. 10, pp. 1280–1287, 1996.
[12]
J. O'Brien, P. Desmond, D. Ames, I. Schweitzer, S. Harrigan, and B. Tress, “A magnetic resonance imaging study of white matter lesions in depression and Alzheimer's disease,” British Journal of Psychiatry, vol. 168, pp. 477–485, 1996.
[13]
A. J. Thomas, J. T. O'Brien, S. Davis et al., “Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study,” Archives of General Psychiatry, vol. 59, no. 9, pp. 785–792, 2002.
[14]
A. J. Thomas and J. T. O'Brien, “Depression and cognition in older adults,” Current Opinion in Psychiatry, vol. 21, no. 1, pp. 8–13, 2008.
[15]
A. Teodorczuk, J. T. O'Brien, M. J. Firbank et al., “White matter changes and late-life depressive symptoms: longitudinal study,” British Journal of Psychiatry, vol. 191, no. 3, pp. 212–217, 2007.
[16]
I. Schweitzer, V. Tuckwell, J. O'Brien, and D. Ames, “Is late onset depression a prodrome to dementia?” International Journal of Geriatric Psychiatry, vol. 17, no. 11, pp. 997–1005, 2002.
[17]
A. Heiden, J. Kettenbach, P. Fischer et al., “White matter hyperintensities and chronicity of depression,” Journal of Psychiatric Research, vol. 39, no. 3, pp. 285–293, 2005.
[18]
H. Lavretsky, L. Zheng, M. W. Weiner et al., “The MRI brain correlates of depressed mood, anhedonia, apathy, and anergia in older adults with and without cognitive impairment or dementia,” International Journal of Geriatric Psychiatry, vol. 23, no. 10, pp. 1040–1050, 2008.
[19]
L. M. Clark, W. M. McDonald, K. A. Welsh-Bohmer et al., “Magnetic resonance imaging correlates of depression in early- and late- onset Alzheimer's disease,” Biological Psychiatry, vol. 44, no. 7, pp. 592–599, 1998.
[20]
I. Hickie, E. Scott, P. Mitchell, K. Wilhelm, M. P. Austin, and B. Bennett, “Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression,” Biological Psychiatry, vol. 42, no. 3, pp. 151–160, 1995.
[21]
I. Hickie, E. Scott, K. Wilhelm, and H. Brodaty, “Subcortical hyperintensities on magnetic resonance imaging in patients with severe depression—A longitudinal evaluation,” Biological Psychiatry, vol. 42, no. 5, pp. 367–374, 1996.
[22]
W. D. Taylor and R. R. Krishnan, “Structural brain investigations in affective disorders,” in Brain Imaging in Affective Disorders, J. C. Soares, Ed., Marcel Dekker, New York, NY, USA, 2003.
[23]
C. E. Coffey, G. S. Figiel, W. T. Djang, and R. D. Weiner, “Subcortical hyperintensity on magnetic resonance imaging: a comparison of normal and depressed elderly subjects,” American Journal of Psychiatry, vol. 147, no. 2, pp. 187–189, 1990.
[24]
B. S. Greenwald, E. Kramer-Ginsberg, K. R. Rama, M. Ashtari, C. Auerbach, and M. Patel, “Neuroanatomic localization of magnetic resonance imaging signal hyperintensities in geriatric depression,” Stroke, vol. 29, no. 3, pp. 613–617, 1998.
[25]
G. S. Alexopoulos, “Frontostriatal and limbic dysfunction in late-life depression,” American Journal of Geriatric Psychiatry, vol. 10, no. 6, pp. 687–695, 2002.
[26]
P. J. Shah, M. F. Glabus, G. M. Goodwin, and K. P. Ebmeier, “Chronic, treatment-resistant depression and right fronto-striatal atrophy,” British Journal of Psychiatry, vol. 180, pp. 434–440, 2002.
[27]
H. C. Chui, “Subcortical ischemic vascular dementia,” Neurologic Clinics, vol. 25, no. 3, pp. 717–740, 2007.
[28]
A. L. Jefferson, D. F. Tate, A. Poppas et al., “Lower cardiac output is associated with greater white matter hyperintensities in older adults with cardiovascular disease,” Journal of the American Geriatrics Society, vol. 55, no. 7, pp. 1044–1048, 2007.
[29]
G. S. Alexopoulos, B. S. Meyers, R. C. Young, S. Campbell, D. Silbersweig, and M. Charlson, “'Vascular depression' hypothesis,” Archives of General Psychiatry, vol. 54, no. 10, pp. 915–922, 1997.
[30]
M. Gatz, L. Fratiglioni, B. Johansson et al., “Complete ascertainment of dementia in the Swedish Twin registry: the HARMONY study,” Neurobiology of Aging, vol. 26, no. 4, pp. 439–447, 2005.
[31]
P. Lichtenstein, U. De Faire, B. Floderus, M. Svartengren, P. Svedberg, and N. L. Pedersen, “The Swedish Twin registry: a unique resource for clinical, epidemiological and genetic studies,” Journal of Internal Medicine, vol. 252, no. 3, pp. 184–205, 2002.
[32]
M. Gatz, C. A. Reynolds, R. John, B. Johansson, J. A. Mortimer, and N. L. Pedersen, “Telephone screening to identify potential dementia cases in a population-based sample of older adults,” International Psychogeriatrics, vol. 14, no. 3, pp. 273–289, 2002.
[33]
M. Gatz, C. Reynolds, J. Nikolic, B. Lowe, M. Karel, and N. Pedersen, “An empirical test of telephone screening to identify potential dementia cases,” International Psychogeriatrics, vol. 14, no. 3, pp. 429–438, 1995.
[34]
G. Blessed, B. E. Tomlinson, and M. Roth, “The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects,” British Journal of Psychiatry, vol. 114, no. 512, pp. 797–811, 1968.
[35]
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric, Washington, DC, USA, 4th edition, 1994.
[36]
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.
[37]
G. C. Roman, 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. 256–260, 1993.
[38]
A. Fiske, M. Gatz, B. Aadn？y, and N. L. Pedersen, “Assessing age of dementia onset: validity of informant reports,” Alzheimer Disease and Associated Disorders, vol. 19, no. 3, pp. 128–134, 2002.
[39]
L. O. Wahlund, F. Barkhof, F. Fazekas et al., “A new rating scale for age-related white matter changes applicable to MRI and CT,” Stroke, vol. 32, no. 6, pp. 1318–1322, 2001.
[40]
J. M. Stevens, C. J. Barber, R. Kerslake, M. Broz, and S. Barter, “Extended use of cranial CT in the evaluation of patients with stroke and transient ischaemic attacks,” Neuroradiology, vol. 33, no. 3, pp. 200–206, 1991.
[41]
K. Lind, M. Jonsson, I. Karlsson, M. Sjogren, A. Wallin, and A. Edman, “Depressive symptoms and white matter changes in patients with dementia,” International Journal of Geriatric Psychiatry, vol. 21, no. 2, pp. 119–125, 2006.
[42]
M. J. Kim, J. P. Hamilton, and I. H. Gotlib, “Reduced caudate gray matter volume in women with major depressive disorder,” Psychiatry Research, vol. 164, no. 2, pp. 114–122, 2008.
[43]
T. Erkinjuntti, L. Ketonen, and R. Sulkava, “Do white matter changes on MRI and CT differentiate vascular dementia from Alzheimer's disease?” Journal of Neurology Neurosurgery and Psychiatry, vol. 50, no. 1, pp. 37–42, 1987.
[44]
K. S. Kendler, M. Gatz, C. O. Gardner, and N. L. Pedersen, “A Swedish national twin study of lifetime major depression,” American Journal of Psychiatry, vol. 163, no. 1, pp. 109–114, 2006.
[45]
L. L. Herrmann, M. Le Masurier, and K. P. Ebmeier, “White matter hyperintensities in late life depression: a systematic review,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 79, no. 6, pp. 619–624, 2008.
[46]
K. R. R. Krishnan, J. C. Hays, L. A. Tupler, L. K. George, and D. G. Blazer, “Clinical and phenomenological comparisons of late-onset and early-onset depression,” American Journal of Psychiatry, vol. 132, no. 5, pp. 785–788, 1995.
[47]
D. P. Devanand, E. Adorno, J. Cheng et al., “Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients,” Journal of Affective Disorders, vol. 78, no. 3, pp. 259–267, 2004.
