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1.
  • Basile, Anna Maria, et al. (author)
  • Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes
  • 2006
  • In: CEREBROVASCULAR DISEASES. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 21:5-6, s. 315-322
  • Journal article (peer-reviewed)abstract
    • <i>Background:</i> Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. <i>Methods:</i> The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1 ± 5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. <i>Results:</i> Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. <i>Conclusions:</i> The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.
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2.
  • Basile, Anna Maria, et al. (author)
  • Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study.
  • 2006
  • In: Cerebrovasc Dis. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 21:5-6, s. 315-22
  • Journal article (peer-reviewed)abstract
    • <i>Background:</i> Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. <i>Methods:</i> The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1 ± 5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. <i>Results:</i> Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. <i>Conclusions:</i> The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.
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3.
  • Bjerke, Maria, 1977, et al. (author)
  • Cerebrovascular Biomarker Profile Is Related to White Matter Disease and Ventricular Dilation in a LADIS Substudy.
  • 2014
  • In: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 4:3, s. 385-94
  • Journal article (peer-reviewed)abstract
    • Small vessel disease (SVD) represents a common often progressive condition in elderly people contributing to cognitive disability. The relationship between cerebrospinal fluid (CSF) biomarkers and imaging correlates of SVD was investigated, and the findings were hypothesized to be associated with a neuropsychological profile of SVD.
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4.
  • Cascini, Silvia, et al. (author)
  • Case Identification and Characterization of Migrants with Dementia in the Lazio Region Using Health Administrative Data
  • 2023
  • In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:3, s. 843-852
  • Journal article (peer-reviewed)abstract
    • Background: A crucial step for planning effective public health policies for migrants with dementia is the collection of data on the local dimensions of the phenomenon and patients’ characteristics.Objective: This study aimed to identify and characterize migrants with dementia in the Lazio region using health administrative databases.Methods: Residents with dementia aged 50 years or older, living in the Lazio region as of December 31, 2018, were identified using a validated algorithm based on hospital discharge(s), claims for antidementia drugs, and co-payment exemption for dementia. Migrants were defined as people born abroad and grouped in migrants from High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs). Overall and age-specific prevalence rates were estimated in native- and foreign-born patients.Results: Dementia was ascertained in 38,460 residents. Among them, 37,280 (96.9%) were born in Italy, 337 (0.9%) were migrants from HDCs, and 843 (2.2%) from HMPCs. Dementia prevalence was higher among natives (1.15%, 95% CI 1.14–1.16) relative to migrants from HDCs (0.60%, 95% CI 0.54–0.67) and HMPCs (0.29%, 95% CI 0.27–0.31). The prevalence of comorbidities did not differ between groups. Migrants with dementia had a lower likelihood of receiving antidementia treatments compared with natives (51.6% in migrants from HDCs, 49.3% in migrants from HMPCs, and 53.5% among Italians).Conclusion: Routinely collected data in healthcare administrative databases can support the identification of migrants with dementia. Migrants exhibited a lower age-standardized prevalence of registered dementia and lower access to dedicated treatments than Italians. These findings are suggestive of underdiagnosis and undertreatment of dementia in migrants.
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5.
  • De Guio, François, et al. (author)
  • Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease
  • 2016
  • In: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X. ; 36:8, s. 1319-1337
  • Research review (peer-reviewed)abstract
    • Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.
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6.
  • Dichgans, Martin, et al. (author)
  • METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration : An initiative of the Joint Programme for Neurodegenerative Disease Research
  • 2016
  • In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:12, s. 1235-1249
  • Journal article (peer-reviewed)abstract
    • Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.
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7.
  • Dyrby, Tim B, et al. (author)
  • Segmentation of age-related white matter changes in a clinical multi-center study.
  • 2008
  • In: NeuroImage. - : Elsevier BV. - 1053-8119. ; 41:2, s. 335-45
  • Journal article (peer-reviewed)abstract
    • Age-related white matter changes (WMC) are thought to be a marker of vascular pathology, and have been associated with motor and cognitive deficits. In the present study, an optimized artificial neural network was used as an automatic segmentation method to produce probabilistic maps of WMC in a clinical multi-center study. The neural network uses information from T1- and T2-weighted and fluid attenuation inversion recovery (FLAIR) magnetic resonance (MR) scans, neighboring voxels and spatial location. Generalizability of the neural network was optimized by including the Optimal Brain Damage (OBD) pruning method in the training stage. Six optimized neural networks were produced to investigate the impact of different input information on WMC segmentation. The automatic segmentation method was applied to MR scans of 362 non-demented elderly subjects from 11 centers in the European multi-center study Leukoaraiosis And Disability (LADIS). Semi-manually delineated WMC were used for validating the segmentation produced by the neural networks. The neural network segmentation demonstrated high consistency between subjects and centers, making it a promising technique for large studies. For WMC volumes less than 10 ml, an increasing discrepancy between semi-manual and neural network segmentation was observed using the similarity index (SI) measure. The use of all three image modalities significantly improved cross-center generalizability compared to neural networks using the FLAIR image only. Expert knowledge not available to the neural networks was a minor source of discrepancy, while variation in MR scan quality constituted the largest source of error.
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8.
  • Firbank, Michael J, et al. (author)
  • White matter hyperintensities and depression--preliminary results from the LADIS study.
  • 2005
  • In: International journal of geriatric psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 20:7, s. 674-9
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: White matter hyperintensities have been associated with the development of depression in older subjects, though the details of this relationship are not fully understood. METHODS: In a pan-European multicentre study of 629 older subjects, we examined the relationship between MRI white matter hyperintensities (WMH), depressive symptoms and self perceived health quality of life (QOL). WMH were rated using a three-point scale. RESULTS: We found depressive symptoms as assessed by the geriatric depression 15-item scale to be associated with WMH rating (Spearman's rho 0.11, p = 0.008) and also with the Euro-QOL health score (Spearman's rho -0.5, p < 0.001). In a ordinal logistic regression model, QOL was found to strongly predict GDS score (p < 0.001) and severe vs mild WMH were associated with increased depression (p = 0.028). The relationship between history of severe depression and WMH score was examined, but there were no differences either between those with and without a history of severe depression, or those with an early vs late onset of depression. CONCLUSIONS: The results suggest that WMH play a role in increasing depressive symptoms, even when perceived quality of life is controlled for as a possible mediating factor.
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9.
  • Gislason, Thorsteinn, et al. (author)
  • Effect of diagnostic criteria on the prevalence of frontotemporal dementia in the elderly
  • 2015
  • In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:4, s. 425-433
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Frontotemporal dementia (FTD) is believed to be rare in the elderly, and the influence of different criteria on the prevalence of FTD is unclear. METHODS: Population-based samples of 70- to 95-year-olds (n = 2462) in Gothenburg, Sweden, underwent neuropsychiatric examinations. Behavioral variant FTD (bvFTD) was diagnosed according to the International Behavioural Variant FTD Criteria Consortium (FTDC), the Frontotemporal Lobe Degeneration Consensus criteria, and the Lund-Manchester Research Criteria. A subset (n = 1074) underwent computerized tomography (CT) of the brain. RESULTS: The prevalence of bvFTD varied between 0.2% and 0.5% at age 70 to 79 years, between 2.5% and 3.6% at age 80 to 89 years, and between 1.7% and 2.2% at age 90 to 95 years. The agreement between different criteria was low to moderate (κ = 0.20-0.42). Among those with bvFTD according to FTDC, 93.3% had frontal and/or temporal lobar atrophy on CT, compared with 12.6% of those without bvFTD (P < .001). CONCLUSIONS: The prevalence of bvFTD was higher than expected in this population. To a large extent, different criteria captured different individuals.
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10.
  • Gouw, Alida A, et al. (author)
  • On the etiology of incident brain lacunes: longitudinal observations from the LADIS study.
  • 2008
  • In: Stroke; a journal of cerebral circulation. - 1524-4628. ; 39:11, s. 3083-5
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND PURPOSE: We investigated regional differences in MRI characteristics and risk factor profiles of incident lacunes over a 3-year period. METHODS: Baseline and 3-year follow-up MRI were collected within the LADIS study (n=358). Incident lacunes were characterized with respect to brain region, their appearance within pre-existent white matter hyperintensities (WMH), surrounding WMH size, and risk factors. RESULTS: 106 incident lacunes were observed in 62 patients (58 subcortical white matter [WM], 35 basal ganglia, and 13 infratentorial). Incident subcortical WM lacunes occurred more often within preexisting WMH (P=0.01) and were mostly accompanied by new and expanded WMH (P<0.001), compared to incident basal ganglia and infratentorial lacunes. Risk factors for incident subcortical WM lacunes were history of hypertension and stroke, whereas atrial fibrillation predicted incident basal ganglia/infratentorial lacunes. CONCLUSIONS: Differences in relation to WMH and risk factor profiles may suggest that incident lacunes in the subcortical WM have a different pathogenesis than those in the basal ganglia and infratentorial region.
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11.
  • Gouw, Alida A, et al. (author)
  • Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study.
  • 2008
  • In: Stroke; a journal of cerebral circulation. - 1524-4628. ; 39:5, s. 1414-20
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND PURPOSE: We studied the natural course of white matter hyperintensities (WMH) and lacunes, the main MRI representatives of small vessel disease, over time and evaluated possible predictors for their development. METHODS: Baseline and repeat MRI (3-year follow-up) were collected within the multicenter, multinational Leukoaraiosis and Disability study (n=396). Baseline WMH were scored on MRI by the Fazekas scale and the Scheltens scale. WMH progression was assessed using the modified Rotterdam Progression scale (absence/presence of progression in 9 brain regions). Baseline and new lacunes were counted per region. WMH and lacunes at baseline and vascular risk factors were evaluated as predictors of WMH progression and new lacunes. RESULTS: WMH progressed (mean+/-SD=1.9+/-1.8) mostly in the subcortical white matter, where WMH was also most prevalent at baseline. The majority of new lacunes, which were found in 19% of the subjects (maximum=9), also appeared in the subcortical white matter, mainly of the frontal lobes, whereas most baseline lacunes were located in the basal ganglia. Baseline WMH and lacunes predicted both WMH progression and new lacunes. Furthermore, previous stroke, diabetes, and blood glucose were risk factors for WMH progression. Male sex, hypertension, systolic blood pressure, previous stroke, body mass index, high-density lipoprotein, and triglyceride levels were risk factors for new lacunes. CONCLUSIONS: WMH and lacunes progressed over time, predominantly in the subcortical white matter. Progression was observed especially in subjects with considerable WMH and lacunes at baseline. Moreover, the presence of vascular risk factors at baseline predicted WMH progression and new lacunes over a 3-year period.
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12.
  • Gudmundsson, Pia, 1978, et al. (author)
  • White Matter Lesions and Temporal Lobe Atrophy Related to incidence of both Dementia and Major Depression in 70-year-olds followed over 10 years
  • 2015
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 22:5, s. 781-788
  • Journal article (peer-reviewed)abstract
    • Abstract Background: A number of studies have suggested associations between dementia and depression in older adults. One reason could be that these disorders share structural correlates, such as white matter lesions (WMLs) and cortical atrophy. No study has examined whether these lesions precede both dementia and depression independently of each other in the general population. Methods: We investigated whether WMLs and cortical atrophy on computed tomography (CT) predict dementia and depression in a population-based sample of 70-year-olds (n=380) followed over 10 years. Exclusion criteria were dementia, major depression, history of stroke and a Mini-Mental State Examination score below 26 at baseline in 2000-01. Dementia was diagnosed according to DSM-III-R and depression according to DSM-5. Primary outcomes included dementia and major depression at 10-year follow-up. Results: Adjusted logistic regression models, including both WMLs and temporal lobe atrophy, showed that moderate-to-severe WMLs (OR 3.96, 95% CI 1.23-12.76) and temporal lobe atrophy (OR 2.93, 95% CI 1.13-7.60) predicted dementia during 10-year follow-up independently of major depression. Similarly, both moderate-to-severe WMLs (OR 3.84, 95% CI 1.25-11.76) and temporal lobe atrophy (OR 2.52, 95% CI 1.06-5.96) predicted depression even after controlling for incident dementia. Conclusion: WMLs and temporal lobe atrophy preceded 10-year incidence of both dementia and depression in 70-year-olds. Shared structural correlates could explain the reported associations between dementia and depression. These brain changes may represent independent and complementary pathways to dementia and depression. Strategies to slow progression of vascular pathology and neurodegeneration could indirectly prevent both dementia and depression in older adults.
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13.
  • Guo, Xinxin, 1972, et al. (author)
  • Blood pressure components and changes in relation to white matter lesions: a 32-year prospective population study.
  • 2009
  • In: Hypertension. - 0194-911X. ; 54:1, s. 57-62
  • Journal article (peer-reviewed)abstract
    • This study aimed to examine the long-term effect of high blood pressure (systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure) on white matter lesions and to study changes in different blood pressure components in relation to white matter lesions. A representative population of women was examined in 1968 and re-examined in 1974, 1980, 1992, and 2000. The presence and severity of white matter lesions on computed tomography were rated by a visual rating scale in 1992 and 2000 in 539 women. Systolic and diastolic blood pressures were measured at all of the examinations. We found that presence and severity of white matter lesions in 1992/2000 were associated with higher diastolic blood pressure and mean arterial pressure at each examination but not with systolic blood pressure and pulse pressure. Odds ratios (95% CIs) for the presence of white matter lesions per 10-mm Hg increase in diastolic pressure were 1.4 (1.0 to 1.9) in 1968, 1.3 (1.0 to 1.8) in 1974, 1.4 (1.1 to 1.9) in 1980, and 1.3 (1.0 to 1.6) in 1992 after adjustment for confounders. The presence of white matter lesions was also associated with a 24-year increase in diastolic pressure (>10 mm Hg), systolic pressure (>40 mm Hg), pulse pressure (>24 mm Hg), and mean arterial pressure (>6 mm Hg; odds ratios [95% CIs]: 2.6 [1.3 to 5.1] for diastolic pressure; 2.0 [1.2 to 3.4] for systolic pressure; 1.8 [1.1 to 2.7] for pulse pressure; and 2.2 [1.4 to 3.4] for mean arterial pressure). Our findings suggest that lowering high diastolic blood pressure and preventing large increases in systolic and diastolic blood pressures may have a protective effect on white matter lesions.
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15.
  • Guo, Xinxin, 1972, et al. (author)
  • Midlife respiratory function related to white matter lesions and lacunar infarcts in late life: the Prospective Population Study of Women in Gothenburg, Sweden.
  • 2006
  • In: Stroke; a journal of cerebral circulation. - 1524-4628. ; 37:7, s. 1658-62
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND PURPOSE: Increased evidence suggests that poor respiratory function increases risk of ischemic damage to the brain. Longitudinal studies on respiratory function and cerebral small-vessel disease are lacking. We examined midlife and late-life respiratory function in relation to small-vessel disease on computed tomography (CT) in women followed for 26 years. METHODS: White matter lesions (WMLs) and lacunar infarcts were rated on brain CT scans in 2000 in 379 women 70 to 92 years of age from a longitudinal population study in Göteborg, Sweden. Respiratory function was measured by peak expiratory flow (PEF) in 1974 and 2000 and by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) in 1980 and 2000. RESULTS: Lower FVC and FEV1 in 1980 and 2000 were associated with presence and severity of WMLs and lacunar infarcts in 2000. Per 1-SD decrease of FVC in 1980, odds ratios (95% CIs) were 1.49 (1.11 to 2.02) for presence of WMLs and 1.95 (1.34 to 2.84) for lacunar infarcts after adjustment for potential confounders. Per 1-SD decrease of FEV1 in 1980, adjusted odds ratios were 1.46 (1.06 to 2.00) for presence of WMLs and 1.42 (1.02 to 1.97) for lacunar infarcts. PEF in 1974 and 2000 was not associated with WMLs or lacunar infarcts. CONCLUSIONS: WMLs and lacunar infarcts in elderly women were related to lower midlife respiratory function. Although our data may not establish causation between lower respiratory function and small-vessel disease, they imply the importance of good respiratory function in midlife.
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18.
  • Johansson, Lena, 1972, et al. (author)
  • Midlife Psychological Distress Associated With Late-Life Brain Atrophy and White Matter Lesions: A 32-Year Population Study of Women.
  • 2012
  • In: Psychosomatic medicine. - 0033-3174. ; 74:2, s. 120-125
  • Journal article (peer-reviewed)abstract
    • Long-standing psychological distress increases the risk of dementia, especially Alzheimer's disease. The present study examines the relationship between midlife psychological distress and late-life brain atrophy and white matter lesions (WMLs), which are common findings on neuroimaging in elderly subjects. A population-based sample of 1462 women, aged 38 to 60 years, was examined in 1968, with subsequent examinations in 1974, 1980, 1992, and 2000. Computed tomography (CT) of the brain was done in 379 survivors in 2000, and of those, 344 had responded to a standardized question about psychological distress in 1968, 1974, and 1980. WMLs, cortical atrophy, and central atrophy (ventricular sizes) were measured at CT scans. Compared with women reporting no distress, those reporting frequent or constant distress at one examination or more (in 1968, 1974, and 1980) more often had moderate-to-severe WMLs (multiadjusted odds ratio = 2.39, 95% confidence interval = 1.16-4.92) and moderate-to-severe temporal lobe atrophy (multiadjusted odds ratio = 2.51, 95% confidence interval = 1.04-6.05) on brain CT in 2000. Frequent/constant distress was also associated with central brain atrophy, that is, higher bicaudate ratio, higher cella media ratio, and larger third-ventricle width. Long-standing psychological distress in midlife increases risks of cerebral atrophy and WMLs on CT in late life. More studies are needed to confirm these findings and to determine potential neurobiological mechanisms of these associations.
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19.
  • Jokinen, Hanna, et al. (author)
  • Longitudinal cognitive decline in subcortical ischemic vascular disease--the LADIS Study.
  • 2009
  • In: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 27:4, s. 384-91
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions. METHODS: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models. RESULTS: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy. CONCLUSIONS: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function.
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20.
  • Jokinen, Hanna, et al. (author)
  • MRI-defined subcortical ischemic vascular disease: baseline clinical and neuropsychological findings. The LADIS Study.
  • 2009
  • In: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 27:4, s. 336-44
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Subcortical ischemic vascular disease (SIVD) is a common, but often overlooked cause of vascular cognitive impairment. Diagnostic research criteria for SIVD are based on magnetic resonance imaging (MRI) findings including substantial white matter lesions (WML) and multiple lacunar infarcts. Empirical studies validating these imaging criteria are still few. The purpose of the study was to describe the clinical and cognitive characteristics of the MRI-defined SIVD in a mixed sample of functionally independent elderly subjects with WML. METHODS: The subjects of the Leukoaraiosis and Disability (LADIS) study, aged 65-84 years, underwent comprehensive clinical and neuropsychological examinations, and brain MRI at the baseline assessment. The subjects meeting the SIVD imaging criteria (n = 89) were compared to the other subjects of the sample (n = 524). RESULTS: SIVD was associated with lower education, hypertension and, independently, with obesity. The subjects with SIVD had more often motor impairment, a history of falls, and subtle impairment in activities of daily living, but they did not differ for depressive symptoms. SIVD subjects performed significantly inferiorly in tests of global cognitive function, psychomotor speed, attention and executive functions, verbal fluency, and working memory. CONCLUSION: In this population of nondisabled older adults with WML, SIVD was related to specific clinical and functional characteristics. Neuropsychological features included psychomotor slowing as well as deficits in attention and executive functions.
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22.
  • Madureira, Sofia, et al. (author)
  • Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly study (LADIS): Experience and baseline data
  • 2006
  • In: NEUROEPIDEMIOLOGY. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 27:2, s. 101-116
  • Journal article (peer-reviewed)abstract
    • The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) involves 11 European centers. It aims to assess the role of the age-related white matter changes as an independent factor in the transition to disability, and in cognitive performance of an independent elderly population. A comprehensive neuropsychological battery was constructed in order to harmonize the cognitive assessment across countries. Patients were evaluated at baseline and during the 3-year follow-up with the Mini-Mental State Examination, a modified version of the VADAS-Cog (Alzheimer’s Dementia Assessment Scale plus tests of Delayed recall, Symbol digit, Digit span, Maze, Digit cancellation and Verbal fluency), Trail making and Stroop test. Six hundred thirty-eight patients (mean age 74 ± 5 years; mean educational level 10 ± 4, F/M: 351/287) were included in this study. Neuropsychological data were analyzed test by test and also grouped in three compound measures (executive, memory and speed/motor control domains). Older subjects (>74 years) performed significantly worse than younger subjects on the ADAS-Mod and on the tests of memory (t<sub>631</sub> = 3.25; p = 0.001), executive functions (t<sub>581</sub> = 4.68; p = 0.001) and speed/motor control (t<sub>587</sub> = 4.01; p = 0.001). Participants with higher educational level (>8 years of school) showed better performances on the compound measures for memory (t<sub>631</sub> = 3.25; p = 0.001), executive functions (t<sub>581</sub> = 4.68; p = 0.001) and speed/motor control (t<sub>587</sub> = 4.01; p = 0.001). Using multiple regression analysis models to study the influence of demographic variables on cognitive performance, age and education remained important variables influencing test performance. In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance.
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23.
  • Madureira, Sofia, et al. (author)
  • Neuropsychological Predictors of Dementia in a Three-Year Follow-Up Period: Data from the LADIS Study
  • 2010
  • In: DEMENTIA AND GERIATRIC COGNITIVE DISORDERS. - 1420-8008. ; 29:4, s. 325-334
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: White matter changes (WMC) are related to cognitive deficits and dementia. Our aim was to determine the extent to which the performance in neuropsychological tests would be able to predict the clinical diagnosis of dementia. METHODS: The LADIS (Leukoaraiosis and Disability) is a prospective study that evaluates the impact of WMC on the transition of independent elderly to disability. The subjects were evaluated at baseline and yearly during 3 years with a comprehensive clinical, functional and neuropsychological protocol. At each visit, dementia was classified according to clinical criteria. The performance in the neuropsychological batteries was compared according to the clinical diagnosis of dementia. RESULTS: From the initially enrolled 639 subjects, 480 were evaluated at year 3. Dementia was diagnosed in 90 participants. The demented subjects had worse performance in almost all the baseline cognitive tests. Using receiver operating characteristic curves, we found that the Vascular Dementia Assessment Scale (VADAS) battery had higher sensitivity and specificity rates (area under the curve = 82%) to identify dementia compared with the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale. Worse performance on baseline MMSE (beta = 0.33; p < 0.001) and VADAS (beta = -0.07; p = 0.02) were predictors of dementia (regression analyses). CONCLUSION: Performance on the MMSE and the VADAS battery were important predictors of dementia at a 3-year period.
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  • Olesen, Pernille J, et al. (author)
  • Temporal lobe atrophy and white matter lesions are related to major depression over 5 years in the elderly.
  • 2010
  • In: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X. ; 35:13, s. 2638-45
  • Journal article (peer-reviewed)abstract
    • The influence of organic brain changes on the development of depression in the elderly is uncertain. Cross-sectional studies, most often from clinical samples, report associations with brain atrophy and cerebrovascular disease, while longitudinal population studies have given mixed results. Our aim was to investigate whether cortical atrophy and white matter lesions (WMLs) on computed tomography (CT) predict occurrence of depression in the elderly. This is a prospective population-based study with 5-year follow-up. The baseline sample included 525 elderly subjects, aged 70-86 years, without dementia or major depression, with a score on the Mini-Mental State Examination above 25, and without dementia at follow-up. Cortical atrophy and WMLs were evaluated at baseline using CT. The main outcome measure was development of major or minor depression at follow-up according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, as evaluated using neuropsychiatric examinations and hospital discharge registers. Logistic regression was used to estimate risk. Over the period of 5 years, 20 individuals developed major and 63 minor depression. Presence of temporal lobe atrophy (odds ratio (OR)=2.81, 95% confidence interval (CI) 1.04-7.62) and moderate-to-severe WMLs (OR=3.21, 95% CI 1.00-10.26) independently predicted major, but not minor, depression after controlling for various confounders. Other brain changes did not predict occurrence of depression. Our findings suggest that temporal lobe atrophy and WMLs represent relatively independent and complementary pathways to major depression in the elderly. This may have implications for prevention, as both neurodegeneration and cerebrovascular disease have been related to preventable factors.
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