Apathy is associated with large-scale white matter network disruption in small vessel disease

Tay, Jonathan; Tuladhar, Anil M.; Hollocks, Matthew J.; Brookes, Rebecca L.; Tozer, Daniel J.; Barrick, Thomas R.; Leeuw, Frank‐Erik de; Markus, Hugh S.

doi:10.1212/wnl.0000000000007095

Cited by 58 publications

(79 citation statements)

References 53 publications

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“…5 Although there is some symptomatic overlap between the two, 6 research using diffusion imaging reported that apathy, but not depression, was associated with white matter network damage in SVD. 3 Many of the white matter pathways underlying apathy overlap with those related to cognitive impairment, and accordingly apathy, rather than depression, has been associated with cognitive deficits in SVD. 7 These results suggest that apathy and cognitive impairment are symptomatic of prodromal dementia in SVD.…”

Section: Introductionmentioning

confidence: 99%

Apathy, but not depression, predicts all-cause dementia in cerebral small vessel disease

Tay

Morris

Tuladhar

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectiveTo determine whether apathy or depression predicts all-cause dementia in small vessel disease (SVD) patients.MethodsAnalyses used two prospective cohort studies of SVD: St. George’s Cognition and Neuroimaging in Stroke (SCANS; n=121) and Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC; n=352). Multivariate Cox regressions were used to predict dementia using baseline apathy and depression scores in both datasets. Change in apathy and depression was used to predict dementia in a subset of 104 participants with longitudinal data from SCANS. All models were controlled for age, education and cognitive function.ResultsBaseline apathy scores predicted dementia in SCANS (HR 1.49, 95% CI 1.05 to 2.11, p=0.024) and RUN DMC (HR 1.05, 95% CI 1.01 to 1.09, p=0.007). Increasing apathy was associated with dementia in SCANS (HR 1.53, 95% CI 1.08 to 2.17, p=0.017). In contrast, baseline depression and change in depression did not predict dementia in either dataset. Including apathy in predictive models of dementia improved model fit.ConclusionsApathy, but not depression, may be a prodromal symptom of dementia in SVD, and may be useful in identifying at-risk individuals.

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Section: Introductionmentioning

confidence: 99%

Apathy, but not depression, predicts all-cause dementia in cerebral small vessel disease

Tay

Morris

Tuladhar

et al. 2020

J Neurol Neurosurg Psychiatry

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“…Early evidence for the vascular apathy hypothesis was reported in studies in clinical samples with established cerebrovascular disease (eg, vascular dementia and stroke), where apathy appeared related to the general effect (or severity) of cerebrovascular damage, given that associations with specific cerebral circuitries and regions were inconsistent . Particularly, the stroke subtype of SVD (lacunar infarcts and white matter hyperintensities [WMH]) was found to be related to apathy in several other studies, independent of depression …”

Section: Introductionmentioning

confidence: 99%

Empirical support for the vascular apathy hypothesis: A structured review

Wouts

Kessel

Beekman

et al. 2019

Int J Geriat Psychiatry

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ObjectivesA systematic review of the relationship between subclinical small vessel disease (SSVD) in the general population and apathy to examine the hypothesis that apathy has a vascular basis.MethodsWe searched for studies on associations between apathy and SSVD, operationalized as white matter hyperintensities (WMH) or white matter diffusivity changes, lacunar infarcts, cerebral microbleeds, decreasing cortical thickness, and perivascular spaces, while also peripheral proxies for SSVD were considered, operationalized as ankle brachial pressure index (ABI), intima media thickness, arterial stiffness, cardio‐femoral pulse wave velocity, hypertension, or cardiovascular disease. Only eligible retrospective and prospective observational studies conducted in the general population were included.ResultsThe 14 studies eligible for review examined the associations between apathy and hypertension (3), ABI (1), arterial stiffness (1), cardiovascular disease (2), WMH (3), white matter diffusivity (2), cerebral microbleeds (1), or cortical thickness (3). Arterial stiffness and white matter diffusivity were not related to apathy, while the associations with cortical thickness were contradictory. Cross‐sectional studies in the general population did find evidence of apathy being associated with WMH, CM, cardiovascular disease, hypertension, and ABI, and cardiovascular disease was prospectively associated with apathy. The methodologies of the studies reviewed were too heterogeneous to perform meta‐analyses.ConclusionsAlthough more prospective evidence is needed and vascular depression needs to be controlled for, cardiovascular disease, hypertension, and ABI as proxies for SSVD, and WMH and cerebral microbleeds as direct measures of SSVD have been found to be associated with apathy in the general population, supporting the hypothesis of vascular apathy.

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“…More than a half of patients included in this study (51.25%) reported symptoms of apathy, while depression, typically recognized as a CSVD manifestation, was leading with 33.75%. Current research on affective status in patients with CSVD also came to similar conclusions, revealing that in some cohorts of patients apathy was the leading symptom in early-stage disease [5,7]. Both apathy and depression were associated with cognitive decline and decrease in quality of life of patients with CSVD, especially in those with dysexecutive syndrome which is one of the major manifestations of the disease [4,5].…”

Section: Discussionmentioning

confidence: 69%

“…Results of self-report screening inventories for apathy and depression have shown excellent correlation with vascular lesions predominantly in white matter, quantified by ARWMC and Fazekas scales. The research of Hollock et al reported that a more intense association exists between white matter lesions and apathy due to disruption of cortico-subcortical pathways [5,7]. Symptoms of apathy are linked to lesions of limbic associative pathways such as anterior cingulate cortex, fornix and fasciculus uncinatus [5,15].…”

Section: Discussionmentioning

confidence: 99%

“…It is possible to overestimate the presence of depression in patients with CSVD, and at same time underestimate the number of cases with apathy. This difference could be clinically significant, because common depression treatment strategies may not target symptoms of apathy [7]. The aim of this study was to analyze affective status in a cohort of inpatients treated for symptomatic CSVD using standard screening tests.…”

Section: Introductionmentioning

confidence: 99%

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Affective status in cerebral small vessel disease

et al. 2019

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Introduction. Cerebral small vessel disease is a neurological condition characterized by motor, cognitive and affective disorders, often found on brain magnetic resonance imaging scans in patients with vascular risk factors. Affective disorders may have a major impact on patients' quality of life, although they are often ignored as an entity in cerebrovascular pathology. Material and Methods. This prospective study included 80 patients with the diagnosis of cerebral small vessel disease admitted at the Clinic of Neurology, Clinical Center of Serbia in the period from January 1, 2017 to January 1, 2019. Baseline demographic data and brain magnetic resonance findings were obtained along with the results of cognitive function and affective status tests. Data were analyzed using standard statistical tests. Results. Standard screening tests revealed that 51.25% and 33.75% of our patients with cerebral small vessel disease suffer from apathy and depression, respectively. A significant correlation was found between the severity of white matter changes on magnetic resonance scans and apathy (p = 0.0092). Additionally, white matter changes were also significantly associated with depression (p = 0.021). Conclusion. Affective disorders are not uncommon in cerebral small vessel disease and apathy was the leading phenomenon among our patients. Since a strong correlation was detected between affective disorders and severity of vascular changes on magnetic resonance scans, we may conclude that both apathy and depression are key features of an underlying brain injury, rather than just comorbidity.

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Apathy is associated with large-scale white matter network disruption in small vessel disease

Cited by 58 publications

References 53 publications

Apathy, but not depression, predicts all-cause dementia in cerebral small vessel disease

Apathy, but not depression, predicts all-cause dementia in cerebral small vessel disease

Empirical support for the vascular apathy hypothesis: A structured review

Affective status in cerebral small vessel disease

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