Baseline characteristic of patients presenting with lacunar stroke and cerebral small vessel disease may predict future development of depression

Pavlovic, Aleksandra; Pekmezović, Tatjana; Trajković, Jasna Zidverc; Medjedovic, Tamara Svabic; Veselinović, N.; Radojičić, Aleksandra; Mijajlović, Milija; Tomić, Gordana; Jovanović, Ž.; Norton, Melanie; Sternic, Nada

doi:10.1002/gps.4289

Cited by 33 publications

(34 citation statements)

References 74 publications

(134 reference statements)

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“…Microbleeds were associated with LLD but not with EOD [146]; these lesions and WMHs were associated with cerebral small vessel disease (CSVD) and reduced cerebral blood flow [148], which predicted depressive disorder in healthy older adults [149]. Depressive symptoms were seen in 10.1–39.8 % of patients with CSVD [2, 150], and patients with silent cerebral infarcts and chronic heart failure had an increased prevalence of MDD compared to those without chronic heart failure [151]; further, minor cerebrovascular incidents predisposed patients to LLD/VaDep [152]. Lacunar infarcts in deep white matter were associated with greater psychomotor retardation, motivation and energy loss, depressed mood, and cognitive decline, presumably due to disruption of frontal–subcortical networks [153, 154], while others suggested that apathy, but not depression in CSVD, is related to damage in circuits associated with emotion regulation [155].…”

Section: Resultsmentioning

confidence: 99%

Vascular depression consensus report – a critical update

Aizenstein

Baskys

Boldrini

et al. 2016

BMC Med

187

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

187

145

View full text Add to dashboard Cite

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“…In both VaD and DM2, the amount of tracer trapped in the brain parenchyma is positively correlated with cognitive deficits in several behavioral tests in rats(30, 34). This would be of interest to WML as these are also associated to cognitive performance(117). Is it possible that glymphatic clearance failure is correlated with WML burden?…”

Section: Altered Glymphatic Function In Svd?mentioning

confidence: 99%

Perivascular spaces, glymphatic dysfunction, and small vessel disease

2017

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Cerebral small vessel diseases (SVD) range broadly in etiology but share a remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces, cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered.

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“…Underlying vascular pathologies are arteriolosclerosis, lipohyalinosis, fibroid necrosis, oedema and damage to the blood-cerebrospinal fluid and blood–brain barriers (BCB/BBB), the latter resulting in chronic leakage of fluid and macromolecules in the white matter and inflammation (reviewed by Kalaria, 2016) [5]. Although SSVD pathogenesis remains poorly understood, it is an age-related condition, associated with a number of risk factors including systemic hypertension [6–9], chronic kidney disease [10, 11], smoking [12], metabolic syndrome [8, 13, 14], osteoporosis [15], chronic obstructive pulmonary disease [16] and sleep-apnoea syndrome [17]. The SSVD clinical manifestations are largely due to complete (lacunes) or incomplete (WML) infarction(s) and microbleeds resulting in cognitive, motor and mood disturbances and eventually functional disability [2], although same lesions might appear in cognitively intact persons during normal ageing.…”

Section: Methodsmentioning

confidence: 99%

Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report

et al. 2017

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BackgroundVascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data.MethodThe group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized.ResultsThis review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer’s disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood–brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau.ConclusionsCombining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.

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Baseline characteristic of patients presenting with lacunar stroke and cerebral small vessel disease may predict future development of depression

Abstract: Baseline functional status and severity of WMH and development of cognitive decline predict the occurence of late-onset depression in patients with SVD.

Cited by 33 publications

References 74 publications

Vascular depression consensus report – a critical update

Vascular depression consensus report – a critical update

Perivascular spaces, glymphatic dysfunction, and small vessel disease

Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report

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