White matter hyperintensities in late life depression: A systematic review

Section of Old Age Psychiatry, Department of Psychiatry, Oxford University, Oxford, UK.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 07/2008; 79(6):619-24. DOI: 10.1136/jnnp.2007.124651
Source: PubMed


White matter hyperintensities in MRI scans are age related but appear to be more prevalent in depressed patients. They may be more pronounced in late onset depression. This finding, if confirmed, would potentially illuminate the heterogeneity of depression in elderly subjects.
We conducted a systematic literature search of studies investigating white matter changes in late life depression, identifying 98 studies. The 30 remaining eligible studies were scrutinised for the presence and severity measures of periventricular and deep white matter changes in late life, late onset and, if available, early onset depression as well as in controls. Comparisons between groups were entered into random effects meta-analyses using odds ratios and Cohen's d, as appropriate. Correlations with potential confounders, such as age difference between groups, were explored.
Late life depression and, to a greater extent, late onset depression in late life were characterised by more frequent and intense white matter abnormalities. In particular, the odds of having white matter changes were over 4 for late compared with early onset depression. Similarly, on severity scales, late onset depression had scores of 0.7-0.8 standard deviations above early onset patients.
Significant differences between early and late onset depression suggest different aetiological mechanisms, in accordance with a theory of "cerebrovascular" depression of late onset. Greater duration of depressive symptoms, signs and treatment does not appear to have a measurable impact on white matter signal in MRI scans.

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    • "To date, the exact mechanism by which subcortical ischemia increases the risk of depression is uncertain. Presumptively, subcortical ischemic lesions may increase the risk of depression do so by damaging to striato-pallido-thalamo-cortical pathways with alterations of the serotonergic and adrenergic circuit (Herrmann et al., 2008). Especially, deep white matter hyperintensities are reported to be associated with developing depression. "
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    ABSTRACT: There are no cross-sectional or longitudinal epidemiological studies present on MRI-defined vascular depression in community populations. The purpose of this study was to estimate the prevalence rates of both vascular and non-vascular late life depression (LLD) at baseline, to examine the natural course of LLD, and to investigate the influence of White matter hyperintensities (WMHs) on depression after three years. The baseline study employed a two-stage design, Phase I population survey (n=783) and Phase II diagnostic evaluation (n=122). In the 3-year follow-up study, baseline participants completing the second phase were reassessed with the same methodology. WMHs severity was rated visually by the modified Fazekas scale and WMHs volume was calculated using an automated method. The prevalence rates of vascular major depressive disorder (MDD) and vascular non-major depressive disorder (nMDD) were 2.39% (56.2% of MDD) and 4.24% (34.0% of nMDD). Subjects with a score of 2 or more on the modified Fazekas scale in either deep white matter hyperintensities or subcortical gray matter ratings had an 8.1 times greater risk of developing a depressive disorder in the 3-year follow-up study. Greater Log WMHs volume (odds ratio=5.78, 95% CI, 1.04-31.72) at baseline was an independent predictor for depressive disorder in the 3-year assessment. Response rate and follow-up rate were relatively low. Vascular depression is common and makes up about a half of MDD in elders. Greater WMHs severity is a crucial factor predicting future depression risk, which supports the previous vascular depression hypothesis. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 07/2015; 180. DOI:10.1016/j.jad.2015.04.008 · 3.38 Impact Factor
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    • "For example, in the only study designed to examine the association between physical activity and WMH, no association was found with total or periventricular WMH; however, an association was found between physical activity and deep WMH. Only two studies used advanced imaging techniques such as diffusion tensor imaging (DTI) (Gow et al., 2012; Tseng et al., 2013), which is superior at assessing white matter integrity and detecting locations where WMH may directly predispose to the development of neuropsychiatric disorders, including depression (Herrmann et al., 2008), cognitive decline, dementia, and stroke (Debette et al., 2010). DTI is used to map and characterize the three-dimensional diffusion of water as a function of spatial location and is therefore a sensitive marker of neuropathology (Alexander, Lee, Lazar, and Field, 2007). "
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    ABSTRACT: Objective: White matter hyperintensities (WMH) are markers of brain white matter injury seen on magnetic resonance imaging. WMH increase with age and are associated with neuropsychiatric disorders. WMH progression can be slowed by controlling vascular risk factors in individuals with advanced disease. Since physical activity can decrease vascular risk factors, physical activity may slow the progression of WMH in individuals without advanced disease, thereby preventing neuropsychiatric disorders. The purpose of this systematic review was to examine the association between physical activity and WMH in individuals without advanced disease. Methods: Articles published in English through March 18, 2014 were searched using PubMed, Web of Science, Cochrane Library and EBSCOhost. Results: Six studies found that more physical activity was associated with less WMH, while 6 found no association. Physical activity is associated with less WMH in individuals without advanced disease when studies are longitudinal or take into consideration physical activity across the lifespan, have a younger sample of older adults, measure different types of physical activity beyond leisure or objectively measure fitness via V02max, measure WMH manually or semi-automatically, and control for risk factors associated with WMH. Conclusion: More physical activity was associated with less white matter hyperintensities in individuals without advanced disease.
    04/2015; 2:319-325. DOI:10.1016/j.pmedr.2015.04.013
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    • "REVIEW ARTICLE has found more intensive and severe white matter hyperintensities in LLD compared with age-matched healthy controls (HCs; e.g., Tupler et al., 2002; Taylor et al., 2003; Sheline et al., 2008; also see Herrmann et al., 2008, for meta-analysis review). White matter hyperintensities can be detected on T2-weighted or fluid-attenuated inversion recovery images. "
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    ABSTRACT: Objectives Late-life depression (LLD) is the association with more cerebrovascular susceptibilities and white matter damage that can be assessed with diffusion tensor imaging (DTI). To better understand the white matter pathological alterations in LLD, we conducted a systematic review and meta-analysis.Methods We searched MEDLINE, EMBASE, PsycINFO, PubMed, and Google Scholar databases for DTI studies comparing patients with LLD and healthy controls. For each study, details regarding participants, imaging methods, and results were extracted. Fractional anisotropy, an index of white matter integrity, was the dependent variable for group comparison. Effect sizes indicating the degree of group difference were estimated by random-effects meta-analysis.ResultsA total of 15 eligible studies were included in the qualitative systematic review, nine of which were suitable for quantitative meta-analyses for the dorsolateral prefrontal cortex (DLPFC), corpus callosum, cingulum, and uncinate fasciculus (UF). Compared with the healthy control group, the LLD group showed lower fractional anisotropy in the DLPFC and UF with a large and a medium effect size, respectively, although heterogeneity and publication bias were found in the DLPFC.Conclusion Diffusion tensor imaging studies of LLD consistently showed reduced anisotropy in the DLPFC and UF of patients with LLD. These damaged regions are located with the frontostriatal and limbic networks. Thus, our findings showed that the disruption of frontal and frontal-to-limbic white matter tracts contributes to the pathogenesis of LLD. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 12/2014; 29(12). DOI:10.1002/gps.4129 · 2.87 Impact Factor
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