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- 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. |
- Madureira, Sofia, et al.
(författare)
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Neuropsychological Predictors of Dementia in a Three-Year Follow-Up Period: Data from the LADIS Study
- 2010
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Ingår i: DEMENTIA AND GERIATRIC COGNITIVE DISORDERS. - 1420-8008. ; 29:4, s. 325-334
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Tidskriftsartikel (refereegranskat)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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| 3. |
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| 4. |
- Simonsen, Anja H., et al.
(författare)
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Pre-analytical factors influencing the stability of cerebrospinal fluid proteins
- 2013
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Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 1872-678X .- 0165-0270. ; 215:2, s. 234-240
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) is a potential source for new biomarkers due to its proximity to the brain. This study aimed to clarify the stability of the CSF proteome when undergoing pre-analytical factors. We investigated the effects of repeated freeze/thaw cycles, protease inhibitors and delayed storage for 4 h, 24 h or 14 days at -20 degrees C, 4 degrees C and room temperature (RT) after centrifugation compared with our standard practice of two hours at RT before placing the samples in an -80 degrees C environment. The results were obtained using immunoassays for amyloid-beta 1-42 (A beta 42), tau, phosphorylated tau (P-tau) and cystatin C and using surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectrometry for proteomic profiling. Tau and P-tau were susceptible to repeated freeze/thaw cycles while SELDI-TOF analysis produced eight significant peaks and additional artefact peaks from samples with added protease inhibitors. Delayed storage for different durations and in different temperatures produced six significant SELDI-TOF peaks. A beta 42 and tau were susceptible to increased temperatures and the duration before storage, whereas P-tau and cystatin C were not. Transthyretin and several of its isoforms were found using SELDI-TOF and were susceptible to freeze/thaw cycles and to increased temperature and length of time prior to storage. We recommend that CSF should be collected and centrifuged immediately after sampling and prior to storage at -80 degrees C without the addition of protease inhibitors. Freeze/thawing should be avoided because of the instability of tau, P-tau and transthyretin. Standardised CSF sampling, handling and storage for biomarker research are essential for accurately comparing the results obtained by different studies and institutions. (c) 2013 Elsevier B.V. All rights reserved.
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| 5. |
- 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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