Cerebral Small Vessel Disease and Association With Higher Incidence of Depressive Symptoms in a General Elderly Population: The AGES-Reykjavik Study

Sloten, Thomas T. van; Sigurðsson, Sigurður; Buchem, Mark A. van; Phillips, Caroline L.; Jónsson, Pálmi V.; Ding, Jie; Schram, Miranda T.; Harris, Tamara B.; Gudnason, Vilmundur; Launer, Lenore J.

doi:10.1176/appi.ajp.2014.14050578

Cited by 119 publications

(131 citation statements)

References 40 publications

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“…Previous studies reported a mean white matter lesion volume of 5 to 11 mL in participants with a mean age of 72 to 75 years. [25][26][27] The prevalence of cerebral microbleeds and lacunar infarcts in our study population (25.0% and 27.6%, respectively) was slightly higher than that in other studies, reporting a prevalence of cerebral microbleeds of 17.2% 27 or 23.5% and a prevalence of lacunar infarcts of 18.2%. 26,28 Although cerebrovascular reactivity may be reduced in persons with small vessel disease, 23,24 BP was not related to CBF in subgroups of persons with overt signs of small vessel diseaserelated pathologies.…”

Section: Discussioncontrasting

confidence: 78%

Blood Pressure Is Not Associated With Cerebral Blood Flow in Older Persons

et al. 2015

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Abstract-Many studies showing a relation between low blood pressure (BP) and adverse health outcomes in older persons suggest that low BP gives rise to reduced cerebral blood flow (CBF). However, limited evidence is available about this association. Baseline data of 203 participants in the Discontinuation of Antihypertensive Treatment in the Elderly (DANTE) trial were used (mean age, 81 years, using antihypertensive medication and with mild cognitive deficits). BP, BP changes on standing, and CBF derived from pseudo-continuous arterial spin-labeling magnetic resonance imaging were assessed in all participants. In 102 participants who were randomly assigned to 4-month continuation (n=47) or discontinuation of antihypertensive treatment (n=55), BP and CBF change were evaluated at 4-month follow-up. Systolic and diastolic BP were not associated with CBF (B=−0.21, P=0.50 and B=−1.07, P=0.07), neither were mean arterial pressure, pulse pressure, and BP changes on standing. In subgroups of participants with small vessel-related cerebral pathologies, including high white matter hyperintensity volume, microbleeds, and lacunar infarcts, or in participants with lower cognition or diabetes mellitus, no association was found between any BP parameters and CBF. Furthermore, compared to the continuation group, CBF change at 4 months was not different in the discontinuation group (B=−0.12, P=0.23). Contrary to the notion that lower BP in old age is associated with decreased CBF, our data do not show this association in older persons using antihypertensive medication and with mild cognitive deficits. Also, this association was not present in subgroups of more vulnerable persons, reflected by small vessel-related cerebral pathologies, lower cognition, or diabetes mellitus.

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Section: Discussioncontrasting

confidence: 78%

Blood Pressure Is Not Associated With Cerebral Blood Flow in Older Persons

et al. 2015

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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

220

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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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“…Therefore, in particular in the pallidum and putamen, dilated Virchow-Robin spaces may be a marker for vascular damage directly caused by high pressure variability and flow pulsatility, as was demonstrated in the AGES-Reykjavik Study. 74 Although the mechanisms by which dilated Virchow–Robin spaces are formed are not completely elucidated, they particularly occur in the pallidum and putamen, in its worst form known as “état criblé” describing diffusely widened perivascular spaces. Widened perivascular spaces are also a common finding in deep white matter in older and/or hypertensive persons.…”

Section: Mri Of Brain Small Vessel Disease and Aortic Functionmentioning

confidence: 99%

Magnetic Resonance Imaging of Cardiovascular Function and the Brain

et al. 2017

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The proximal aorta acts as a coupling device between heart and brain perfusion, modulating the amount of pressure and flow pulsatility transmitted into the cerebral microcirculation. Stiffening of the proximal aorta is strongly associated with age and hypertension. The detrimental effects of aortic stiffening may result in brain damage as well as heart failure. The resulting cerebral small vessel disease and heart failure may contribute to early cognitive decline and (vascular) dementia. This pathophysiological sequence of events underscores the role of cardiovascular disease as a contributory mechanism in causing cognitive decline and dementia and potentially may provide a starting point for prevention and/or treatment. Magnetic resonance imaging (MRI) is well suited to assess the function of the proximal aorta and the left ventricle (e.g. aortic arch pulse wave velocity and distensibility) as well as the various early and late manifestations of cerebral small vessel disease (e.g. microbleeds and white matter hyperintensities in strategically important regions of the brain). Specialized MRI techniques are explored for diagnosing preclinical changes in white matter integrity or brain microvascular pulsatility. This review discusses the potential role of MRI for evaluating the pathophysiology of proximal aortic function with aging and the interaction between aortic function and brain perfusion, as a contributing mechanism to cerebral small vessel disease, resulting in early cognitive decline and vascular dementia.

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Cerebral Small Vessel Disease and Association With Higher Incidence of Depressive Symptoms in a General Elderly Population: The AGES-Reykjavik Study

Cited by 119 publications

References 40 publications

Blood Pressure Is Not Associated With Cerebral Blood Flow in Older Persons

Blood Pressure Is Not Associated With Cerebral Blood Flow in Older Persons

Vascular depression consensus report – a critical update

Magnetic Resonance Imaging of Cardiovascular Function and the Brain

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