| 1. |
- Antila, Kari, et al.
(författare)
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The PredictAD project : development of novel biomarkers and analysis software for early diagnosis of the Alzheimer's disease
- 2013
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Ingår i: Interface Focus. - : The Royal Society Publishing. - 2042-8898 .- 2042-8901. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most common cause of dementia affecting 36 million people worldwide. As the demographic transition in the developed countries progresses towards older population, the worsening ratio of workers per retirees and the growing number of patients with age-related illnesses such as AD will challenge the current healthcare systems and national economies. For these reasons AD has been identified as a health priority, and various methods for diagnosis and many candidates for therapies are under intense research. Even though there is currently no cure for AD, its effects can be managed. Today the significance of early and precise diagnosis of AD is emphasized in order to minimize its irreversible effects on the nervous system. When new drugs and therapies enter the market it is also vital to effectively identify the right candidates to benefit from these. The main objective of the PredictAD project was to find and integrate efficient biomarkers from heterogeneous patient data to make early diagnosis and to monitor the progress of AD in a more efficient, reliable and objective manner. The project focused on discovering biomarkers from biomolecular data, electrophysiological measurements of the brain and structural, functional and molecular brain images. We also designed and built a statistical model and a framework for exploiting these biomarkers with other available patient history and background data. We were able to discover several potential novel biomarker candidates and implement the framework in software. The results are currently used in several research projects, licensed to commercial use and being tested for clinical use in several trials.
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| 2. |
- Basile, Anna Maria, et al.
(författare)
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Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes
- 2006
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Ingår i: CEREBROVASCULAR DISEASES. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 21:5-6, s. 315-322
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Tidskriftsartikel (refereegranskat)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. |
- Basile, Anna Maria, et al.
(författare)
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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
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Ingår i: Cerebrovasc Dis. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 21:5-6, s. 315-22
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Dyrby, Tim B, et al.
(författare)
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Segmentation of age-related white matter changes in a clinical multi-center study.
- 2008
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119. ; 41:2, s. 335-45
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Frisoni, Giovanni B, et al.
(författare)
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The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium.
- 2008
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 4:4, s. 255-64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). METHODS: Seven academic sites of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic resonance imaging (MRI) scans, cerebrospinal fluid, and blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater by using visual rating scales. RESULTS: Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioral, and neuropsychological features of the European subjects were very similar to their U.S. counterparts. Three-dimensional T1-weighted MRI sequences were successfully performed on all subjects, and cerebrospinal fluid samples were obtained from 77%, 68%, and 83% of AD patients, MCI patients, and controls, respectively. Mean MTA score showed a significant increase from controls (left, right: 0.4, 0.3) to MCI patients (0.9, 0.8) to AD patients (2.3, 2.0), whereas mean WMH score did not differ among the three diagnostic groups (between 0.7 and 0.9). The distribution of both MRI markers was comparable to matched US-ADNI subjects. CONCLUSIONS: Academic EADC centers can adopt the ADNI platform to enroll MCI and AD patients and older controls with global cognitive and structural imaging features remarkably similar to those of the US-ADNI.
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| 6. |
- Gouw, Alida A, et al.
(författare)
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On the etiology of incident brain lacunes: longitudinal observations from the LADIS study.
- 2008
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Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628. ; 39:11, s. 3083-5
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Gouw, Alida A, et al.
(författare)
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Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study.
- 2008
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Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628. ; 39:5, s. 1414-20
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Herukka, Sanna-Kaisa, et al.
(författare)
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Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment.
- 2017
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 13:3, s. 285-295
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Tidskriftsartikel (refereegranskat)abstract
- This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling.
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