The impact of subcortical white matter disease on mood in euthymic older adults: a diffusion tensor imaging study.

OBJECTIVES Clinical depression in the elderly is associated with cerebral small vessel disease. It is less certain whether the endorsement of depressive symptoms in the absence of clinical depression, relatively common in euthymic older adults, is also associated with white matter damage. The majority of studies exploring this issue have produced mixed results, perhaps due, in part, to differences in defining the threshold for depression, notating vascular risk factors, and/or the neuroimaging tools used to quantify white matter damage. We aimed to address these issues with non-demented euthymic older adults. DESIGN AND PARTICIPANTS We performed diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) in a population based cohort of 79 individuals (mean age = 68 years). MEASUREMENTS In addition to neuroimaging, the authors report assessments of overall cognition, executive functioning, and depression. RESULTS Scores on the Geriatric Depression Scale 15-item (GDS-15) correlated with DTI measures of mean diffusivity (r [77] = 0.23, p = 0.039) and fractional anisotropy (r [77] = -0.22, p = 0.045) but only approached significance for T2-weighted MRI measures of white matter hyperintensities (WMH; r [77] = 0.21, p = 0.053). After adjusting for factors known to influence the development of WMH and depression, including age and vascular risks, DTI-derived indices of white matter integrity remained significantly associated with GDS-15 scores. Furthermore, only DTI-derived measures of white matter integrity contributed to the variance in GDS-15 scores in logistical regression modeling. CONCLUSIONS These findings demonstrate an association between white matter damage and the endorsement of depressive symptoms in euthymic older adults and suggest that DTI may be more sensitive to this damage than T2-WMH in an aging cohort with multiple vascular risk factors.

[1]  G. Alexopoulos Role of executive function in late-life depression. , 2003, The Journal of clinical psychiatry.

[2]  C. Reynolds,et al.  Relationship of deep white matter hyperintensities and apolipoprotein E genotype to depressive symptoms in older adults without clinical depression. , 2001, The American journal of psychiatry.

[3]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[4]  Katja Petrovic,et al.  White matter hyperintensities rather than lacunar infarcts are associated with depressive symptoms in older people: the LADIS study. , 2006, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[5]  J. O'Brien,et al.  A volumetric study of MRI signal hyperintensities in late-life depression. , 2004, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[6]  A. Hofman,et al.  Incidence and recurrence of late-life depression. , 2008, Archives of general psychiatry.

[7]  Anthony R. McIntosh,et al.  Limbic–frontal circuitry in major depression: a path modeling metanalysis , 2004, NeuroImage.

[8]  W. Markesbery,et al.  AD lesions and infarcts in demented and non‐demented Japanese‐American men , 2005, Annals of neurology.

[9]  Faith M. Gunning-Dixon,et al.  Aging of cerebral white matter: a review of MRI findings , 2009, International journal of geriatric psychiatry.

[10]  Martin Bland,et al.  An Introduction to Medical Statistics , 1987 .

[11]  G. Alexopoulos,et al.  Executive dysfunction in geriatric depression. , 2002, The American journal of psychiatry.

[12]  Casey Crump,et al.  Cerebrovascular Disease and Evolution of Depressive Symptoms in the Cardiovascular Health Study , 2002, Stroke.

[13]  C. A. Clark,et al.  A structural equation modeling investigation of age-related variance in executive function and DTI measured white matter damage , 2008, Neurobiology of Aging.

[14]  R O'Carroll,et al.  Estimating premorbid intellectual level in dementia using the National Adult Reading Test: a Canadian study. , 1991, The British journal of clinical psychology.

[15]  R. Bryant,et al.  Psychosocial Approaches of Acute Stress Reactions , 2005, CNS Spectrums.

[16]  G. Alexopoulos,et al.  'Vascular depression' hypothesis. , 1997, Archives of general psychiatry.

[17]  M. Catani,et al.  The impact of region-specific leukoaraiosis on working memory deficits in dementia , 2008, Neuropsychologia.

[18]  Assessing for depression and mood disturbance in later life. , 2004, British journal of community nursing.

[19]  M. Izal,et al.  The Geriatric Depression Scale: A Review of Its Development and Utility , 1996, International Psychogeriatrics.

[20]  R. Alexandrowicz,et al.  The criterion validity of the Geriatric Depression Scale: a systematic review , 2006, Acta psychiatrica Scandinavica.

[21]  Arthur MacNeill Horton,et al.  Wechsler Memory Scale III , 1999 .

[22]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[23]  R. Dean,et al.  TEST REVIEW: Dean C. Delis, Edith Kaplan & Joel H. Kramer, Delis Kaplan Executive Function System (D-KEFS), The Psychological Corporation, San Antonio, TX, 2001. $415.00 (complete kit) , 2006 .

[24]  Chris A Clark,et al.  White matter pathway asymmetry underlies functional lateralization. , 2006, Cerebral cortex.

[25]  D. A. Grant,et al.  A behavioral analysis of degree of reinforcement and ease of shifting to new responses in a Weigl-type card-sorting problem. , 1948, Journal of experimental psychology.

[26]  A. Hofman,et al.  Cerebral white matter lesions and depressive symptoms in elderly adults. , 2000, Archives of general psychiatry.

[27]  Babak A. Ardekani,et al.  Macromolecular white matter abnormalities in geriatric depression: a magnetization transfer imaging study. , 2008 .

[28]  A. Hofman,et al.  Cerebral white matter lesions, vascular risk factors, and cognitive function in a population‐based study , 1994, Neurology.

[29]  A Hofman,et al.  Cerebral white matter lesions and atherosclerosis in the Rotterdam Study , 1993, The Lancet.

[30]  J. O'Brien,et al.  White matter hyperintensities and depression—preliminary results from the LADIS study , 2005, International journal of geriatric psychiatry.

[31]  Scott T. Grafton,et al.  Automated image registration: I. General methods and intrasubject, intramodality validation. , 1998, Journal of computer assisted tomography.

[32]  K. Tragl,et al.  Data from the VITA Study do not support the concept of vascular depression. , 2006, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[33]  J. H. Steiger Tests for comparing elements of a correlation matrix. , 1980 .

[34]  R B D'Agostino,et al.  Probability of stroke: a risk profile from the Framingham Study. , 1991, Stroke.

[35]  J. Mazziotta,et al.  Automated image registration , 1993 .

[36]  H S Markus,et al.  Brief cognitive assessment for patients with cerebral small vessel disease , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[37]  M. van Buchem,et al.  Progression of cerebral white matter lesions is not associated with development of depressive symptoms in elderly subjects at risk of cardiovascular disease. The PROSPER Study , 2006, International journal of geriatric psychiatry.

[38]  H. Christensen,et al.  MRI hyperintensities and depressive symptoms in a community sample of individuals 60-64 years old. , 2005, The American journal of psychiatry.

[39]  N. Raz,et al.  Aging white matter and cognition: Differential effects of regional variations in diffusion properties on memory, executive functions, and speed , 2009, Neuropsychologia.

[40]  Y. Sheline Neuroimaging studies of mood disorder effects on the brain , 2003, Biological Psychiatry.

[41]  G. Alexopoulos,et al.  Clinical presentation of the "depression-executive dysfunction syndrome" of late life. , 2002, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[42]  J. Stroop Studies of interference in serial verbal reactions. , 1992 .

[43]  F. Fazekas,et al.  Pathologic correlates of incidental MRI white matter signal hyperintensities , 1993, Neurology.

[44]  K. Krishnan,et al.  Cerebrovascular disease and depression symptoms in the cardiovascular health study. , 1999, Stroke.

[45]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[46]  J. Yesavage,et al.  Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version. , 1986 .

[47]  H. Markus,et al.  The cognitive profiles of CADASIL and sporadic small vessel disease , 2006, Neurology.