Multimodal MRI markers support a model of small vessel ischemia for depressive symptoms in very old adults

Tudorascu, Dana L.; Rosano, Caterina; Venkatraman, Vijay K.; MacCloud, Rebecca L.; Harris, Tamara B.; Yaffe, Kristine; Newman, Anne B.; Aizenstein, Howard J.

doi:10.1016/j.pscychresns.2014.08.009

Cited by 16 publications

(40 citation statements)

References 40 publications

(42 reference statements)

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“…In very old adults with depression, loss of grey matter volume was most significant in the bilateral insula and anterior cerebral cortex, supporting a cerebrovascular pattern of LLD [133]. These changes, together with WMHs, are associated with both depression and cognitive decline and may precede the incidence of both disorders in elders by 10 years [134], suggesting an etiological pathway from ischemia to increased depressive burden [133].…”

Section: Resultsmentioning

confidence: 99%

Vascular depression consensus report – a critical update

Aizenstein

Baskys

Boldrini

et al. 2016

BMC Med

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182

145

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BackgroundVascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition – a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term “MRI-defined vascular depression”.DiscussionThis diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal–subcortical–limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed.ConclusionThe multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

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Section: Resultsmentioning

confidence: 99%

Vascular depression consensus report – a critical update

Aizenstein

Baskys

Boldrini

et al. 2016

BMC Med

Self Cite

182

145

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“…However interpreting these findings requires considering other evidence which demonstrates that periventricular, deep brain, and overall WMH are all highly correlated, and that an arbitrary, categorical distinction between periventricular and deep brain WMHs is not empirically supported (75); this study suggests WMHs extended smoothly out from the ventricles as a function of increasing overall burden. Consistent with these observations, a recent population-based study demonstrated that depression was associated with WMH accumulation around the ventricles (76), and another recent study found the ratio of WMH to non-WMH tissue differed between depressed patients and controls only in the upper cingulum (77). …”

Section: The Relevance Of Wmh Extent and Localizationmentioning

confidence: 58%

“…Voxel-based research similarly suggests LLD is associated with lower FA across multiple white matter tracts including those implicated in cognitive and affective processing (76, 79). Network based analysis of DTI data suggests LLD is associated with reduced connectivity of temporal regions (80).…”

Section: Tract Specific and Whole-brain White Matter Microstructural mentioning

confidence: 98%

“…One study found depression was associated with lower levels of grey matter volume across multiple regions, but most significantly in the insula and anterior cingulate cortex (76). Cortical thickness may also differ between LLD patients and controls; for example, lower cortical thickness has been noted among LLD patients in right frontal, parietal, and temporal brain regions (82).…”

Section: Grey Matter Structure and Network Organizationmentioning

confidence: 99%

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Brain Structural Connectivity in Late-Life Major Depressive Disorder

Smagula

Aizenstein

2016

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Disrupted brain connectivity might explain both the pathogenesis and consequences of late-life major depressive disorder (LLD). However, it remains difficult to ascertain whether and how specific circuits are affected. We reviewed literature regarding brain connectivity in LLD, and we specifically focused on the role of structural pathology. LLD is associated with greater levels of cerebrovascular disease, and greater levels of cerebrovascular disease are associated with both depression development and treatment responsiveness. Cerebrovascular disease is most often measured as white matter hyperintensity (WMH) burden, and histopathology studies suggest WMH reflect myelin damage and fluid accumulation (among other underlying pathology). WMHs appear as confluent caps around the ventricles (periventricular), as well as isolated lesions in the deep white matter. The underlying tissue damage and implications for brain connectivity may differ by WMH location or severity. WMHs are associated with lower white matter microstructural integrity (measured with diffusion tensor imaging) and altered brain function (measured with functional MRI). LLD is also associated with lower white matter microstructural integrity and grey matter loss which may also alter the network properties and function of the brain. Damage to brain structure reflected by WMH, reduced white matter microstructural integrity, and atrophy may affect brain function, and are therefore likely pathophysiological mechanisms of LLD. Additional research is needed to fully characterize the developmental course and pathology underlying these imaging markers, and to understand how structural damage explains LLD's various clinical manifestations.

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“…In this study, we used a group of older adults enrolled in a study of late-life depression (LLD). As depression in older adults is associated with the presence of small vessel ischemic disease (Alexopoulos, 2006; Taylor et al, 2013; Tudorascu et al, 2014) this group is likely to have a significant burden of WMH, and thus is well-suited for testing how WMH burden interfere with tissue segmentation and registration. In general, aging populations tend to have higher WMH burden, but patients with LLD often have an even higher WMH burden compared to age-matched healthy controls (Herrmann et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The effects of white matter disease on the accuracy of automated segmentation

Karim

Andreescu

MacCloud

et al. 2016

Psychiatry Research: Neuroimaging

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Automated segmentation of the brain is challenging in the presence of brain pathologies such as white matter hyperintensities (WMH). A late-life depression population was used to demonstrate the effect of WMH on brain segmentation and normalization. We used an automated algorithm to detect WMH, and either filled them with normal-appearing white-matter (NAWM) intensities or performed a multi-spectral segmentation, and finally compared the standard approach to the WMH filling or multi-spectral segmentation approach using intra-class correlation coefficients (ICC). The presence of WMH affected segmentations for both approaches suggesting that studies investigating structural differences in populations with high WMH should account for WMH. We also investigated how functional data contrasts are affected using normalization between the standard compared to fill and multi-spectral approach. We found that the functional data was not affected. While replication with a larger sample is needed, this study shows that WMH can significantly affect the results of segmentation and these areas are not limited to those affected by WMH. It is clear that to study gray matter differences that some correction should be made to account for WMH. Future studies should investigate which methods for accounting for WMH are most effective.

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Multimodal MRI markers support a model of small vessel ischemia for depressive symptoms in very old adults

Cited by 16 publications

References 40 publications

Vascular depression consensus report – a critical update

Vascular depression consensus report – a critical update

Brain Structural Connectivity in Late-Life Major Depressive Disorder

The effects of white matter disease on the accuracy of automated segmentation

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