Association of Microvascular Dysfunction With Late-Life Depression

Agtmaal, Marnix J.M. van; Houben, Alfons J.H.M.; Pouwer, Frans; Stehouwer, Coen D. A.; Schram, Miranda T.

doi:10.1001/jamapsychiatry.2017.0984

Cited by 213 publications

(167 citation statements)

References 149 publications

(448 reference statements)

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“…The FRS BMI was selected for this study due to the increased risk of metabolic syndrome in Mexican Americans. Van Agtmaal et al [62] argue that white matter hyperintensities are caused by damage to the endothelium of the blood vessel, which causes endothelial dysfunction. Endothelial dysfunction can be caused by cardiovascular conditions such as hypertension, diabetes, and smoking.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Vascular Depression and Cognition in Mexican Americans

Johnson¹,

Large

Munoz

et al. 2019

Dement Geriatr Cogn Disord

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Background: Mexican Americans are at increased risk of developing mild cognitive impairment (MCI) and Alzheimer’s disease compared to non-Hispanic whites. This study sought to examine the relationship between vascular risk, depression, and cognition in Mexican American elders. Methods: Data from 470 (390 normal controls, 80 MCI patients) Mexican Americans enrolled in the Health and Aging Brain among Latino Elders (HABLE) study were used. The cardiovascular risk was assessed by the Framingham Risk Score. Cognition was assessed with a neuropsychological battery, and depression was assessed based on scores from the Geriatric Depression Scale (GDS). ANOVAs were utilized to determine the differences in neuropsychological scores of normal controls with and without depression and CVD risk (low vs. high). Follow-up logistic regression was conducted to determine MCI risk. Results: The results of this study indicated that comorbid depression and a high CVD risk were associated with poorer cognitive performance in Mexican Americans. Depressed women with high CVD risk were more likely to have executive dysfunction, language deficits, and poorer global cognition than nondepressed women with a high CVD risk. In Mexican American men, those with a high vascular risk and depression were more likely to have executive dysfunction and poorer immediate memory than the nondepressed high-risk group. Higher GDS scores (OR = 1.10; 95% CI 1.02–1.10, p = 0.001) and higher vascular risk scores (OR = 1.05; 95% CI 1.02–1.10, p = 0.001) significantly predicted MCI status in Mexican Americans. Conclusion: The results of this study indicated that comorbid depression and a high CVD risk were associated with poorer cognitive performance and increased risk of MCI in Mexican Americans.

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Section: Discussion/conclusionmentioning

confidence: 99%

Vascular Depression and Cognition in Mexican Americans

Johnson¹,

Large

Munoz

et al. 2019

Dement Geriatr Cogn Disord

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“…But although Queen Victoria was asymptomatic in the period between her two depressions, cerebrovascular damage had been accruing, conceivably over a period of years, beneath the surface of her ostensible remission. These cerebrovascular insults could have involved silent infarcts or reduced perfusion in vital circuitry, or both, but their net effect was likely to have produced inflammatory and other pathological processes that compromised the function of the reward and cognitive control systems of the brain . The cerebrovascular changes were in turn exacerbated by the neurological repercussions of multiple losses, effects that might have included compromises in dendritic complexity, neurogenesis, and functional connectivity.…”

Section: Discussionmentioning

confidence: 99%

“…The Queen's first depression, while different in acuity and presentation from the later one, had prognostic implications. Individuals with a history of depression, that is, persons who have a confirmed vulnerability to depressive manifestations, are prone to develop significant affective symptoms when they have experienced cerebrovascular insults, usually in the later decades of life . Another possibility is that for persons with prior histories of depression there may be a lower threshold severity of vascular events and personal losses required for the recurrence of depressive symptoms in old age.…”

Section: Discussionmentioning

confidence: 99%

Vascular depression and the death of Queen Victoria

Abrams

Alexopoulos

2018

Int J Geriat Psychiatry

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Objectives The aim of this article was to examine relationships between the neurological events that were the immediate cause of the death of Queen Victoria and the late‐life depression that preceded it. Methods/Design The authors closely reviewed the surviving medical notes of Queen Victoria's personal physician, Sir James Reid,Bt. recorded during the Queen's last 10 days of life. These notes were summarized in a chronological narrative and their implications considered in light of current concepts of vascular depression. Results The depression that Queen Victoria experienced over the 5 months prior to her death and during her final 10 days from 13 January 1901 until 22 January likely had a vascular etiology. Conclusions Although conclusions from this study are necessarily speculative given the lack of neuroimaging and other diagnostic tools available in 1901, it emerged that Queen Victoria had experienced early‐onset depression followed in later life by an acute depressive episode associated with vascular risk factors and personal losses, a sequence also encountered by today's geriatricians. In addition, etiological connections between the Queen's early‐onset and late‐life depressions appeared probable. Underlined for contemporary practitioners are the suffering experienced by patients with vascular depression at the end of their lives, as well as the struggles of physicians like Sir James Reid to provide clinical wisdom and emotional support.

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“…As the disease presents in older subjects with MDD, the decrease in the length of SERT-ir axons in comparison to younger subjects with MDD may reflect pathology in the ascending serotonin axonal input to the prefrontal cortex. These axons ascending from serotonin cell bodies in the brainstem may be damaged in older depressed subjects as they pass through the internal capsule and corona radiata where enhanced deep white matter hyperintensities are localized in older subjects with depression and less so in age-matched control subjects (Krishnan et al, 1988; Rabins et al, 1991; O’Brien et al, 1996; Thomas et al, 2002; Tupler et al, 2002; Hornung, 2003; van Agtmaal et al, 2017). …”

Section: Discussionmentioning

confidence: 99%

“…The 5HTTLPR genotype was also assessed as there is evidence that the 5HTTLPR polymorphism affects SERT expression (Lesch et al, 1996). Older subjects with MDD have more frontal deep white matter hyperintensities than age- matched controls (Krishnan et al, 1988; Rabins et al, 1991; O’Brien et al, 1996; Thomas et al, 2002; Tupler et al, 2002; van Agtmaal et al, 2017). Increases with age in deep white matter hyperintensities in depression may induce pathology in ascending serotonergic axons from the midbrain raphe system projecting to the OFC.…”

Section: Introductionmentioning

confidence: 97%

Length of axons expressing the serotonin transporter in orbitofrontal cortex is lower with age in depression

et al. 2017

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Studies of major depressive disorder (MDD) in postmortem brain tissue report enhanced binding to inhibitory serotonin-1A autoreceptors in midbrain dorsal raphe and reductions in length of axons expressing the serotonin transporter (SERT) in dorsolateral prefrontal cortex. The length density of axons expressing SERT in the orbitofrontal cortex (OFC) was determined in 18 subjects with MDD and 17 age-matched control subjects. A monoclonal antibody was used to immunohistochemically label the SERT in fixed sections of OFC. The 3-dimensional length density of SERT-immunoreactive (ir) axons in layer VI of OFC was estimated. The age of subjects with MDD was negatively correlated with SERT axon length (r=−0.77, p<0.0005). The significant effect of age persisted when removing four depressed subjects with an antidepressant medication present at the time of death, or when removing nine depressed subjects that had a recent prescription for an antidepressant medication. Neither gender, tissue pH, postmortem interval, 5-HTTLPR genotype, time in fixative, nor death by suicide had a significant effect on axon length. The age-related decrease in SERT-ir axon length in MDD may reflect pathology of ascending axons passing through deep white matter hyperintensities. Greater length of axons expressing SERT in younger subjects with MDD may result in a significant deficit in serotonin availability in OFC.

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Association of Microvascular Dysfunction With Late-Life Depression

Cited by 213 publications

References 149 publications

Vascular Depression and Cognition in Mexican Americans

Vascular Depression and Cognition in Mexican Americans

Vascular depression and the death of Queen Victoria

Length of axons expressing the serotonin transporter in orbitofrontal cortex is lower with age in depression

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