White matter changes and late-life depressive symptoms

Teodorczuk, Andrew; O’Brien, John T.; Firbank, Michael; Pantoni, Leonardo; Poggesi, Anna; Erkinjuntti, Timo; Wallin, Anders; Wahlund, Lars‐Olof; Gouw, Alida A.; Waldemar, Gunhild; Schmidt, Reinhold; Ferro, José M.; Chabriat, Hugues; Bäzner, Hansjörg; Inzitari, Domenico

doi:10.1192/bjp.bp.107.036756

Cited by 135 publications

(97 citation statements)

References 32 publications

(37 reference statements)

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“…Cross-sectional associations between WMLs and depression have been shown repeatedly, especially for MRI and mainly from clinical studies (Greenwald et al, 1998;Ikram et al, 2010;Kumar et al, 2000;Kumar et al, 2002), although not all studies support this association (Rainer et al, 2006;Skoog et al, 1994). Our finding that WMLs preceded major depression is in agreement with three previous longitudinal studies using MRI (Godin et al, 2008;Steffens et al, 2002;Teodorczuk et al, 2007). However, two longitudinal population-based studies did not support this association (Ikram et al, 2010;Versluis et al, 2006).…”

Section: Discussionsupporting

confidence: 84%

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Temporal Lobe Atrophy and White Matter Lesions are Related to Major Depression over 5 years in the Elderly

Olesen

Gustafson

Simoni

et al. 2010

Neuropsychopharmacol

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The influence of organic brain changes on the development of depression in the elderly is uncertain. Cross-sectional studies, most often from clinical samples, report associations with brain atrophy and cerebrovascular disease, while longitudinal population studies have given mixed results. Our aim was to investigate whether cortical atrophy and white matter lesions (WMLs) on computed tomography (CT) predict occurrence of depression in the elderly. This is a prospective population-based study with 5-year follow-up. The baseline sample included 525 elderly subjects, aged 70-86 years, without dementia or major depression, with a score on the Mini-Mental State Examination above 25, and without dementia at follow-up. Cortical atrophy and WMLs were evaluated at baseline using CT. The main outcome measure was development of major or minor depression at follow-up according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, as evaluated using neuropsychiatric examinations and hospital discharge registers. Logistic regression was used to estimate risk. Over the period of 5 years, 20 individuals developed major and 63 minor depression. Presence of temporal lobe atrophy (odds ratio (OR) ¼ 2.81, 95% confidence interval (CI) 1.04-7.62) and moderate-to-severe WMLs (OR ¼ 3.21, 95% CI 1.00-10.26) independently predicted major, but not minor, depression after controlling for various confounders. Other brain changes did not predict occurrence of depression. Our findings suggest that temporal lobe atrophy and WMLs represent relatively independent and complementary pathways to major depression in the elderly. This may have implications for prevention, as both neurodegeneration and cerebrovascular disease have been related to preventable factors.

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Section: Discussionsupporting

confidence: 84%

“…The results from longitudinal population-based studies are conflicting. Three studies using MRI reported that WMLs increased the risk of subsequent depression (Godin et al, 2008;Steffens et al, 2002;Teodorczuk et al, 2007) while two could not confirm these findings (Ikram et al, 2010;Versluis et al, 2006).…”

Section: Introductionmentioning

confidence: 98%

Temporal Lobe Atrophy and White Matter Lesions are Related to Major Depression over 5 years in the Elderly

Olesen

Gustafson

Simoni

et al. 2010

Neuropsychopharmacol

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“…LADIS consistently demonstrated significant differences between the performance of patients with punctate changes when compared with those with early confluent and confluent changes with the latter always being most impaired. Such relationships were seen for all clinical correlates, including cognition [87], depression [86], gait and balance [4], as well as urinary incontinence [56]. Most importantly, early confluent and to a greater extent confluent white matter abnormalities predicted functional decline in activities of daily living during a relatively short observational period of 3 years [37].…”

Section: Risk Factors and Key Clinical Findingsmentioning

confidence: 92%

Heterogeneity in age-related white matter changes

et al. 2011

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White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of

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“…49,50 Depression frequently occurs in the early stages of AD and may result from both cell loss in key areas of the brain controlling emotions as well as a psychological reaction to cognitive loss. 4 Vascular changes such as white matter hyperintensities are a risk factor for both depression 51,52 and dementia, 53 and are associated with a high prevalence of depression in cross-sectional studies 54 . In our sensitivity analysis that excluded patients with an ICD-9 diagnosis of dementia in the 2 years after baseline, depression remained associated with an increased risk of dementia, suggesting that depression was less likely to be a prodromal symptom or secondary to dementia.…”

Section: Discussionmentioning

confidence: 99%

Comorbid Depression Is Associated with an Increased Risk of Dementia Diagnosis in Patients with Diabetes: A Prospective Cohort Study

et al. 2010

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White matter changes and late-life depressive symptoms

Abstract: White matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life.

Cited by 135 publications

References 32 publications

Temporal Lobe Atrophy and White Matter Lesions are Related to Major Depression over 5 years in the Elderly

Temporal Lobe Atrophy and White Matter Lesions are Related to Major Depression over 5 years in the Elderly

Heterogeneity in age-related white matter changes

Comorbid Depression Is Associated with an Increased Risk of Dementia Diagnosis in Patients with Diabetes: A Prospective Cohort Study

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