| 231. |
- ten Kate, M., et al.
(författare)
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MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study
- 2018
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: With the shift of research focus towards the pre-dementia stage of Alzheimer's disease (AD), there is an urgent need for reliable, non-invasive biomarkers to predict amyloid pathology. The aim of this study was to assess whether easily obtainable measures from structural MRI, combined with demographic data, cognitive data and apolipoprotein E (APOE) epsilon 4 genotype, can be used to predict amyloid pathology using machine-learning classification. Methods: We examined 810 subjects with structural MRI data and amyloid markers from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, including subjects with normal cognition (CN, n = 337, age 66.5 +/- 72, 50% female, 27% amyloid positive), mild cognitive impairment (MCI, n = 375, age 69. 1 +/- 7.5, 53% female, 63% amyloid positive) and AD dementia (n = 98, age 67.0 +/- 7.7, 48% female, 97% amyloid positive). Structural MRI scans were visually assessed and Freesurfer was used to obtain subcortical volumes, cortical thickness and surface area measures. We first assessed univariate associations between MRI measures and amyloid pathology using mixed models. Next, we developed and tested an automated classifier using demographic, cognitive, MRI and APOE epsilon 4 information to predict amyloid pathology. A support vector machine (SVM) with nested 10-fold cross-validation was applied to identify a set of markers best discriminating between amyloid positive and amyloid negative subjects. Results: In univariate associations, amyloid pathology was associated with lower subcortical volumes and thinner cortex in AD-signature regions in CN and MCI. The multi-variable SVM classifier provided an area under the curve (AUC) of 0.81 +/- O. 07 in MCI and an AUC of 0.74 +/- 0.08 in CN. In CN, selected features for the classifier included APOE epsilon 4, age, memory scores and several MRI measures such as hippocampus, amygdala and accumbens volumes and cortical thickness in temporal and parahippocampal regions. In MCI, the classifier including demographic and APOE epsilon 4 information did not improve after additionally adding imaging measures. Conclusions: Amyloid pathology is associated with changes in structural MRI measures in CN and MCI. An automated classifier based on clinical, imaging and APOE epsilon 4 data can identify the presence of amyloid pathology with a moderate level of accuracy. These results could be used in clinical trials to pre-screen subjects for anti-amyloid therapies.
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| 232. |
- Teodorczuk, A., et al.
(författare)
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Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study.
- 2009
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Ingår i: Psychological medicine. - 1469-8978. ; 40:4, s. 603-610
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growing 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. RESULTS: Baseline 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). CONCLUSIONS: Our 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.
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| 233. |
- Teodorczuk, A., et al.
(författare)
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White matter changes and late-life depressive symptoms - Longitudinal study
- 2007
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Ingår i: BRITISH JOURNAL OF PSYCHIATRY. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 191, s. 212-217
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear.AimsTo investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders.MethodIn a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year.ResultsUsing logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (P<0.01).ConclusionsWhite 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.
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| 234. |
- Thorvaldsson, Valgeir, 1976, et al.
(författare)
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Memory in individuals with mild cognitive impairment in relation to APOE and CSF Abeta42.
- 2010
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Ingår i: International psychogeriatrics / IPA. - 1741-203X. ; 22:4, s. 598-606
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The epsilon4 allele of the apolipoprotein E (APOE) gene and low levels of cerebrospinal fluid (CSF) amyloid beta-proteins 42 (Abeta) have previously been associated with increased risk of cognitive decline in old age. In this study we examine the interaction of these markers with episodic memory in a sample identified as having mild cognitive impairment (MCI). METHODS: The sample (N = 149) was drawn from the Gothenburg MCI study and measured according to three free recall tests on three occasions spanning over four years. Second-order Latent Curve Models (LCM) were fitted to the data. RESULTS: Analyses accounting for age, gender, education, APOE, Abeta42, and interaction between APOE and Abeta42 revealed that the epsilon4 allele was significantly associated with level of memory performance in the presence of low Abeta42 values (< or = 452 ng/L). Associations between memory performance and Abeta42 were significant among the epsilon4 carriers but not among the non-carriers. The Abeta42 marker was, however, significantly associated with changes in memory over the study time period in the total sample. CONCLUSION: The findings support the hypothesis of an interactive effect of APOE and Abeta42 for memory decline in MCI patients.
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| 235. |
- Verdelho, A., et al.
(författare)
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Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: the LADIS study
- 2013
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 84:11, s. 1250-1254
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Tidskriftsartikel (refereegranskat)abstract
- Objective Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC). Methods The LADIS (Leukoaraiosis And DISability in the elderly) prospective study evaluated the impact of WMC on the transition of independent older subjects into disability. Subjects were evaluated annually over a 3 year period with a comprehensive clinical and neuropsychological evaluation. Previous episodes of depression and current DS were assessed during each interview. Severity of DS was assessed using the self-rated 15 item Geriatric Depression Scale. A neuropsychological battery and clinical criteria for cognitive impairments were applied in all clinical visits, and cognitive compound measures were made based on neuropsychological results. MRI was performed at baseline and at year 3. Results 639 subjects were included (74.1 +/- 5 years old, 55% women, 9.6 +/- 3.8 years of schooling). Dementia was diagnosed in 90 patients and cognitive impairment not dementia in 147 patients at the last clinical evaluation. DS were an independent predictor of cognitive impairment (dementia and not dementia) during follow-up, independent of the effect of the severity of WMC, medial temporal lobe atrophy, age, education or global cognitive function at baseline. Conclusions DS are associated with an increase risk of cognitive decline, independent of the effect of WMC, probably due to an additive or synergistic effect. In this context, DS probably represent a subtle ongoing organic dysfunction
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| 236. |
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| 237. |
- Verdelho, A., et al.
(författare)
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Physical Activity Prevents Progression for Cognitive Impairment and Vascular Dementia Results From the LADIS (Leukoaraiosis and Disability) Study
- 2012
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 43:12, s. 3331-3335
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. Methods-The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria. Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. Results-Six hundred thirty-nine subjects were included (74.1 +/- 5 years old, 55% women, 9.6 +/- 3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia (vascular dementia, 54; Alzheimer disease with vascular component, 34; frontotemporal dementia, 2), and 147 had cognitive impairment not dementia. Using Cox regression analysis, physical activity reduced the risk of cognitive impairment (dementia and not dementia: beta=-0.45, P=0.002; hazard ratio, 0.64; 95% CI, 0.48-0.85), dementia (beta=-0.49, P=0.043; hazard ratio, 0.61; 95% CI, 0.38-0.98), and vascular dementia (beta=-0.86, P=0.008; hazard ratio, 0.42; 95% CI, 0.22-0.80), independent of age, education, white matter change severity, medial temporal atrophy, previous and incident stroke, and diabetes. Conclusions-Physical activity reduces the risk of cognitive impairment, mainly vascular dementia, in older people living independently. (Stroke. 2012; 43: 3331-3335.)
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| 238. |
- Verdelho, Ana, et al.
(författare)
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Self-Perceived Memory Complaints Predict Progression to Alzheimer Disease. The LADIS Study.
- 2011
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Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877 .- 1875-8908. ; 27:3, s. 491-498
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Tidskriftsartikel (refereegranskat)abstract
- Memory complaints are frequent in the elderly but its implications in cognition over time remain a controversial issue. Our objective was to evaluate the risk of self perceived memory complaints in the evolution for future dementia. The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes (WMC) on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Dementia and subtypes of dementia were classified. Self perceived memory complaints in independent elderly were collected during the interview. MRI was performed at entry and at the end of the study. 639 subjects were included (74.1 ± 5 years old, 55% women, 9.6 ± 3.8 years of schooling). At end of follow-up, 90 patients were demented (vascular dementia, 54; Alzheimer's disease (AD) and AD with vascular component, 34; frontotemporal dementia, 2). Using Cox regression analysis, we found that self perceived memory complaints were a strong predictor of AD and AD with vascular component during the follow-up (β = 2.7, p = 0.008; HR = 15.5, CI 95% [2.04, 117.6]), independently of other confounders, namely depressive symptoms, WMC severity, medial temporal lobe atrophy, and global cognition status at baseline. Self perceived memory complaints did not predict vascular dementia. In the LADIS study, self perceived memory complaints predicted AD but not vascular dementia in elderly subjects with WMC living independently.
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| 239. |
- Verdelho, A., et al.
(författare)
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White matter changes and diabetes predict cognitive decline in the elderly The LADIS Study
- 2010
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 75:2, s. 160-167
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We aimed to study if age-related white matter changes (WMC) and vascular risk factors were predictors of cognitive decline in elderly subjects with WMC living independently. METHODS: The Leukoaraiosis and Disability prospective multinational European study (LADIS) evaluates the impact of WMC on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Additionally, dementia, subtypes of dementia, and cognitive decline without dementia were classified according to usual clinical criteria. MRI was performed at entry and at the end of the study. RESULTS: A total of 639 subjects were included (74.1 +/- 5 years, 55% women, 9.6 +/- 3.8 years of schooling). At end of follow-up, 90 patients had dementia and 147 had cognitive impairment no dementia. Using Cox regression analysis, WMC severity independently predicted cognitive decline (dementia and not dementia), independently of age, education, and medial temporal atrophy (MTA). Diabetes at baseline was the only vascular risk factor that independently predicted cognitive decline during follow-up, controlling for age, education, WMC severity, and temporal atrophy. Considering subtypes of dementia, Alzheimer disease (AD) was predicted only by MTA, while vascular dementia was predicted by previous stroke, WMC severity, and MTA. CONCLUSION: WMC severity and diabetes are independent predictors of cognitive decline in an initially nondisabled elderly population. Vascular dementia is predicted by previous stroke and WMC, while AD is predicted only by MTA.
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