| 1. |
- Firbank, M. J., et al.
(författare)
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Relationship between progression of brain white matter changes and late-life depression: 3-year results from the LADIS study
- 2012
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 201:1, s. 40-45
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Tidskriftsartikel (refereegranskat)abstract
- Background Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear. Aims To investigate the relationship between baseline and incident depression and progression of white matter changes. Method In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale. Results Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline. Conclusions Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.
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| 2. |
- Schmidt, R., et al.
(författare)
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White Matter Lesion Progression in LADIS Frequency, Clinical Effects, and Sample Size Calculations
- 2012
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 43:10, s. 2643-2647
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. Methods-Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale. Results-WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm. Conclusions-WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure. (Stroke. 2012; 43:2643-2647.)
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| 3. |
- van der Flier, W. M., et al.
(författare)
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Vascular cognitive impairment
- 2018
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Ingår i: Nature Reviews Disease Primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The term vascular cognitive impairment (VCI) was introduced around the start of the new millennium and refers to the contribution of vascular pathology to any severity of cognitive impairment, ranging from subjective cognitive decline and mild cognitive impairment to dementia. Although vascular pathology is common in elderly individuals with cognitive decline, pure vascular dementia (that is, dementia caused solely by vascular pathology) is uncommon. Indeed, most patients with vascular dementia also have other types of pathology, the most common of which is Alzheimer disease (specifically, the diffuse accumulation of amyloid-beta plaques and neurofibrillary tangles composed of tau). At present, the main treatment for VCI is prevention by treating vascular diseases and other risk factors for VCI, such as hypertension and diabetes mellitus. Despite the current paucity of disease-modifying pharmacological treatments, we foresee that eventually, we might be able to target specific brain diseases to prevent cognitive decline and dementia.
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| 4. |
- Benisty, S, et al.
(författare)
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Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study.
- 2009
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:5, s. 478-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. METHODS: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. RESULTS: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (beta = -0.61; p = 0.043), and worse compound scores for speed and motor control (beta = -0.25; p = 0.006), executive functions (beta = -0.19; p = 0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/pallidum and the memory compound Z score (beta = -0.13; p = 0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. CONCLUSION: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH.
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| 5. |
- Jokinen, H., et al.
(författare)
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Brain atrophy accelerates cognitive decline in cerebral small vessel disease The LADIS study
- 2012
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Ingår i: Neurology. - 0028-3878. ; 78:22, s. 1785-1792
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the independent contributions and combined interactions of medial temporal lobe atrophy (MTA), cortical and subcortical atrophy, and white matter lesion (WML) volume in longitudinal cognitive performance. Methods: A total of 477 subjects with age-related WML were evaluated with brain MRI and annual neuropsychological examinations in 3-year follow-up. Baseline MRI determinants of cognitive decline were analyzed with linear mixed models controlling for multiple confounders. Results: MTA and subcortical atrophy predicted significantly steeper rate of decline in global cognitive measures as well as compound scores for psychomotor speed, executive functions, and memory after adjusting for age, gender, education, lacunes/infarcts, and WML volume. Cortical atrophy independently predicted decline in psychomotor speed. WML volume remained significantly associated with cognitive decline even after controlling for the atrophy scores. Moreover, significant synergistic interactions were found between WML and atrophy measures in overall cognitive performance across time and the rate of cognitive decline. Synergistic effects were also observed between baseline lacunar infarcts and all atrophy measures on change in psychomotor speed. The main results remained robust after exclusion of subjects with clinical stroke or incident dementia, and after additional adjustments for progression of WML and lacunes. Conclusions: Brain atrophy and WML are independently related to longitudinal cognitive decline in small vessel disease. MTA, subcortical, and cortical atrophy seem to potentiate the effect of WML and lacunes on cognitive decline. Neurology (R) 2012;78:1785-1792
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| 6. |
- Jokinen, H, et al.
(författare)
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Incident lacunes influence cognitive decline: the LADIS study.
- 2011
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 76:22, s. 1872-8
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Tidskriftsartikel (refereegranskat)abstract
- In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML.
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