Impact of white matter hyperintensity location on depressive symptoms in memory-clinic patients: a lesion–symptom mapping study

Leeuwis, Anna E.; Weaver, Nick A.; Biesbroek, J. Matthijs; Exalto, Lieza G.; Kuijf, Hugo J.; Hooghiemstra, Astrid M.; Prins, Niels D.; Scheltens, Philip; Barkhof, Frederik; Flier, Wiesje M. van der; Biessels, Geert Jan

doi:10.1503/jpn.180136

Cited by 10 publications

(7 citation statements)

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“…35 Furthermore, lesions in specific white matter tracts, such as the forceps minor and the cortical spinal tract, have also been associated with depressive symptoms. 36 Future studies on the association between lesion location and neuropsychological and neuropsychiatric symptoms in patients with VCD should replicate our findings.…”

Section: Discussionsupporting

confidence: 61%

Comorbid amyloid‐β pathology affects clinical and imaging features in VCD

Leijenaar

Groot

Sudre

et al. 2020

Alzheimer's & Dementia

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Introduction:To date, the clinical relevance of comorbid amyloid-(A ) pathology in patients with vascular cognitive disorders (VCD) is largely unknown. Methods:We included 218 VCD patients with available cerebrospinal fluid A 42 levels.Patients were divided into A + mild-VCD (n = 84), A − mild-VCD (n = 68), A + major-VCD (n = 31), and A − major-VCD (n = 35). We measured depression with the Geriatric Depression Scale, cognition with a neuropsychological test battery and derived white matter hyperintensities (WMH) and gray matter atrophy from MRI. Results:A − patients showed more depressive symptoms than A +. In the major-VCD group, A − patients performed worse on attention (P = .02) and executive functioning (P = .008) than A +. We found no cognitive differences in patients with mild VCD. In the mild-VCD group, A − patients had more WMH than A + patients, whereas conversely, in the major-VCD group, A + patients had more WMH. Atrophy patterns did not differ between A + and A − VCD group.Discussion: Comorbid A pathology affects the manifestation of VCD, but effects differ by severity of VCD.

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Section: Discussionsupporting

confidence: 61%

Comorbid amyloid‐β pathology affects clinical and imaging features in VCD

Leijenaar

Groot

Sudre

et al. 2020

Alzheimer's & Dementia

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“…following the “vascular depression” hypothesis) (40,41). White matter hyperintensities located in (pre)frontal and temporal regions have been associated with depressive symptoms (42–45), which aligns with locations identified in our disconnectome-based analyses. This suggests that vascular damage to the fronto-limbic circuits represents a common mechanism of depressive symptoms in cerebral small vessel disease and acute ischemic stroke (5).…”

Section: Discussionsupporting

confidence: 85%

Strategic infarct locations for post-stroke depressive symptoms: a lesion- and disconnection-symptom mapping study

Weaver

Lim

Schilderinck

et al. 2021

Preprint

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BackgroundDepression is the most common neuropsychiatric complication after stroke. Infarct location is associated with post-stroke depressive symptoms (PSDS), but it remains debated which brain structures are critically involved. We performed a large-scale lesion-symptom mapping study to identify infarct locations, and white matter disconnections, associated with PSDS.MethodsWe included 553 patients (age 69±11 years, 42% female) with acute ischemic stroke. PSDS were measured using the 30-item Geriatric Depression Scale (GDS-30). Multivariable support vector regression (SVR)-based analyses were performed both at the level of individual voxels (SVR-VLSM) and predefined regions of interest (SVR-ROI) to relate infarct location to PSDS. We externally validated our findings in an independent stroke cohort (N=459). Finally, disconnectome-based analyses were performed using SVR-VLSM, in which white matter fibers disconnected by the infarct were analyzed instead of the infarct itself. Results: Infarcts in the right amygdala, right hippocampus and right pallidum were consistently associated with PSDS (permutation-based p<0.05) in SVR-VLSM and SVR-ROI. External validation (N=459) confirmed the association between infarcts in the right amygdala and pallidum, but not the right hippocampus, and PSDS. Disconnectome-based analyses revealed that disconnections in the right parahippocampal white matter, right thalamus and pallidum, and right anterior thalamic radiation were significantly associated (permutation-based p<0.05) with PSDS.ConclusionsInfarcts in the right amygdala and pallidum, and disconnections of right limbic and frontal cortico-basal ganglia-thalamic circuits, are associated with PSDS. Our findings provide a comprehensive and integrative picture of strategic infarct locations for PSDS, and shed new light on pathophysiological mechanisms of depression after stroke.

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“…They may include structural damage to neural networks (30,85) or a shared inflammatory pathogenesis (86). Much research in this focuses on "pure" vascular/subcortical dementia, focusing, for example, on white matter lesions (87)(88)(89). Much fewer studies have explicitly evaluated neuropsychiatric profiles of MXD vs.…”

Section: Other Neuropsychiatric Symptoms As Related To Severity Of Cognitive Declinementioning

confidence: 99%

Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia Due to AD: Relation With Disease Stage and Cognitive Deficits

et al. 2021

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Background: The interaction between neuropsychiatric symptoms, mild cognitive impairment (MCI), and dementia is complex and remains to be elucidated. An additive or multiplicative effect of neuropsychiatric symptoms such as apathy or depression on cognitive decline has been suggested. Unraveling these interactions may allow the development of better prevention and treatment strategies. In the absence of available treatments for neurodegeneration, a timely and adequate identification of neuropsychiatric symptom changes in cognitive decline is highly relevant and can help identify treatment targets.Methods: An existing memory clinic-based research database of 476 individuals with MCI and 978 individuals with dementia due to Alzheimer's disease (AD) was reanalyzed. Neuropsychiatric symptoms were assessed in a prospective fashion using a battery of neuropsychiatric assessment scales: Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale (30 items). We subtyped subjects suffering from dementia as mild, moderate, or severe according to their Mini-Mental State Examination (MMSE) score and compared neuropsychiatric scores across these groups. A group of 126 subjects suffering from AD with a significant cerebrovascular component was examined separately as well. We compared the prevalence, nature, and severity of neuropsychiatric symptoms between subgroups of patients with MCI and dementia due to AD in a cross-sectional analysis.Results: Affective and sleep-related symptoms are common in MCI and remain constant in prevalence and severity across dementia groups. Depressive symptoms as assessed by the CSDD further increase in severe dementia. Most other neuropsychiatric symptoms (such as agitation and activity disturbances) progress in parallel with severity of cognitive decline. There are no significant differences in neuropsychiatric symptoms when comparing “pure” AD to AD with a significant vascular component.Conclusion: Neuropsychiatric symptoms such as frontal lobe symptoms, psychosis, agitation, aggression, and activity disturbances increase as dementia progresses. Affective symptoms such as anxiety and depressive symptoms, however, are more frequent in MCI than mild dementia but otherwise remain stable throughout the cognitive spectrum, except for an increase in CSDD score in severe dementia. There is no difference in neuropsychiatric symptoms when comparing mixed dementia (defined here as AD + significant cerebrovascular disease) to pure AD.

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Impact of white matter hyperintensity location on depressive symptoms in memory-clinic patients: a lesion–symptom mapping study

Cited by 10 publications

References 40 publications

Comorbid amyloid‐β pathology affects clinical and imaging features in VCD

Comorbid amyloid‐β pathology affects clinical and imaging features in VCD

Strategic infarct locations for post-stroke depressive symptoms: a lesion- and disconnection-symptom mapping study

Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia Due to AD: Relation With Disease Stage and Cognitive Deficits

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