Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: the LADIS study

Aims:Depressive symptoms (DS) in the elderly have been implicated in cognitive decline, and are more frequent in patients with white matter changes (WMC). Our aim was to ascertain if DS influence cognition in an elderly population with WMC.Methods:The LADIS (Leukoaraiosis and Disability) is a prospective European study that evaluates the impact of WMC on the transition of independent elderly subjects into disability. Subjects were enrolled due to minor complaints without impact in daily-living activities, and presence of WMC. Subjects were evaluated at baseline and yearly during 3 years with a comprehensive clinical and functional protocol. DS were recorded with the Geriatric Depression Scale (GDS). Major depression was classified according to the DSM-IV criteria. Dementia and cognitive decline not dementia were diagnosed according to usual clinical criteria. MRI was performed at entry and at the end of the study. WMC severity was rated according to the Fazeka's scale.Results:639 subjects were included (74.1 ± 5 years old, 55% women, 9.6±3.8 years of schooling). 89% (568), 78.4% (501), and 75% (480) of the patients from the initial sample were followed-up in clinical visit at year 1, 2 and 3. At the end of the study 90 patients were demented and 147 patients had cognitive impairment not dementia. Using survival Cox regression we found that depressive symptoms were independent predictors of cognitive impairment independently of age, education, gender, WMC severity and temporal atrophy.Conclusion:Depressive symptoms are independent predictor of cognitive decline in an independent elderly population with WMC.

Download Full-text

Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study

Psychological Medicine ◽

10.1017/s0033291709990857 ◽

2009 ◽

Vol 40 (4) ◽

pp. 603-610 ◽

Cited By ~ 79

Author(s):

A. Teodorczuk ◽

M. J. Firbank ◽

L. Pantoni ◽

A. Poggesi ◽

T. Erkinjuntti ◽

...

Keyword(s):

Depressive Symptoms ◽

White Matter ◽

Regression Models ◽

Community Sample ◽

Late Life ◽

Cerebral White Matter ◽

White Matter Changes ◽

Baseline Severity ◽

Causal Pathway ◽

Depressive Episodes

BackgroundGrowing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults.MethodIn the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors.ResultsBaseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08).ConclusionsOur results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.

Download Full-text

Effect of the Interaction Between Hypertension and Cerebral White Matter Changes on the Progression of Alzheimer Disease

Current Alzheimer Research ◽

10.2174/1567205015666181002141013 ◽

2018 ◽

Vol 15 (14) ◽

pp. 1354-1360 ◽

Cited By ~ 4

Author(s):

Ping-Song Chou ◽

Yi-Hui Kao ◽

Meng-Ni Wu ◽

Mei-Chuan Chou ◽

Chun-Hung Chen ◽

...

Keyword(s):

White Matter ◽

Alzheimer Disease ◽

Rating Scale ◽

Vital Role ◽

Independent Effect ◽

Cerebral White Matter ◽

Clinical Dementia Rating ◽

White Matter Changes ◽

Age Related ◽

The Mean

Background: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. Objective: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. Method: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). Results: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. Conclusion: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

Download Full-text

Cerebral white matter changes in deficit and non-deficit subtypes of schizophrenia

Journal of Neural Transmission ◽

10.1007/s00702-020-02207-w ◽

2020 ◽

Vol 127 (7) ◽

pp. 1073-1079

Author(s):

An Sen Tan ◽

Qian Hui Chew ◽

Kang Sim

Keyword(s):

White Matter ◽

Cerebral White Matter ◽

White Matter Changes

Download Full-text

Serial Clinical and MRI Study of Diffuse Cerebral White Matter Changes in Multiple Sclerosis

Imaging of Brain Metabolism Spine and Cord Interventional Neuroradiology Free Communications ◽

10.1007/978-3-642-74337-5_119 ◽

1989 ◽

pp. 419-423 ◽

Cited By ~ 1

Author(s):

M. Brainin ◽

Th. Reisner ◽

E. Maida ◽

A. Neuhold ◽

L. Wicke ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Cerebral White Matter ◽

White Matter Changes ◽

Mri Study

Download Full-text

098 A case of delayed post-hypoxic leukoencephalopathy complicating drug overdose

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-anzan.86 ◽

2019 ◽

Vol 90 (e7) ◽

pp. A32.1-A32

Author(s):

Min Fong ◽

Nicholas Rigby ◽

Paul Pun ◽

Roger Mitchell ◽

Daniel Schweitzer ◽

...

Keyword(s):

White Matter ◽

Single Case ◽

Neuropsychiatric Symptoms ◽

Bipolar Affective Disorder ◽

Cerebral White Matter ◽

High Signal ◽

White Matter Changes ◽

Hypoxic Event ◽

Diffusion Weighted Images ◽

Single Case Report

IntroductionDelayed post-hypoxic leukoencephalopathy (DPHL) is a syndrome characterised by neurological deterioration following a period of recovery after an initial hypoxic event with striking white-matter change on magnetic resonance imaging. We present a case characterised by insidious onset and a fluctuating course of cognitive and neuropsychiatric symptoms.MethodsSingle case report.ResultsA 61 year old lady, with a background history of previously well managed bipolar affective disorder, was found unresponsive following an intentional overdose of temazepam and tramadol. She was hypotensive, hypoxic and required ventilatory and inotropic support. Following extubation, the patient had residual left-sided weakness and MRI confirmed a right frontal watershed infarction. A three week period of clinical improvement was followed by marked deterioration firstly with fluctuating mood and other neuropsychiatric symptoms which progressed to severe impairment of cognition and alertness. There was generalised slowing on the EEG and the CSF was unremarkable. Repeat neuroimaging undertaken on day 41 of the admission, revealed new symmetric and confluent cerebral white matter changes with high signal on the Diffusion Weighted Images (DWI) and Fluid Attenuated Inversion Recovery (FLAIR) images. The patient was managed with supportive care and sustained a clinically significant recovery (MOCA 26/30), despite ongoing cognitive impairments including working memory and deficits in social cognition including mood instability and disinhibition. Repeat neuroimaging 3 months after initial presentation revealed partial resolution of the white matter changes.ConclusionA diagnosis of DPHL should be considered in patients with variable mood and cognition following initial improvement after a hypoxic event.

Download Full-text