WO2006063644A1 - Verfahren und vorrichtung zur spektroskopischen untersuchung von körperflüssigkeiten und gewebeproben hinsichtlich eines erhöhten alzheimerverdachts - Google Patents
Verfahren und vorrichtung zur spektroskopischen untersuchung von körperflüssigkeiten und gewebeproben hinsichtlich eines erhöhten alzheimerverdachts Download PDFInfo
- Publication number
- WO2006063644A1 WO2006063644A1 PCT/EP2005/012151 EP2005012151W WO2006063644A1 WO 2006063644 A1 WO2006063644 A1 WO 2006063644A1 EP 2005012151 W EP2005012151 W EP 2005012151W WO 2006063644 A1 WO2006063644 A1 WO 2006063644A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sample
- parameter
- alzheimer
- infrared spectrum
- measured
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 21
- 210000001124 body fluid Anatomy 0.000 title claims abstract description 18
- 239000010839 body fluid Substances 0.000 title claims abstract description 18
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 16
- 238000001228 spectrum Methods 0.000 claims abstract description 23
- 238000002329 infrared spectrum Methods 0.000 claims abstract description 22
- 210000004369 blood Anatomy 0.000 claims abstract description 8
- 239000008280 blood Substances 0.000 claims abstract description 8
- 238000011156 evaluation Methods 0.000 claims description 21
- 206010012289 Dementia Diseases 0.000 claims description 3
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 201000004810 Vascular dementia Diseases 0.000 claims description 2
- 238000005259 measurement Methods 0.000 claims description 2
- 230000008447 perception Effects 0.000 claims 1
- 238000004458 analytical method Methods 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000013528 artificial neural network Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 238000007621 cluster analysis Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000012706 support-vector machine Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/40—Detecting, measuring or recording for evaluating the nervous system
- A61B5/4076—Diagnosing or monitoring particular conditions of the nervous system
- A61B5/4088—Diagnosing of monitoring cognitive diseases, e.g. Alzheimer, prion diseases or dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
- A61B5/7271—Specific aspects of physiological measurement analysis
- A61B5/7275—Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H10/00—ICT specially adapted for the handling or processing of patient-related medical or healthcare data
- G16H10/40—ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
- G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
- G16H50/30—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indices; for individual health risk assessment
Definitions
- the invention relates to a method and a device for the spectroscopic examination of human tissue samples and body fluids, in particular blood, with regard to an increased Alzheimer suspected.
- Alzheimer's is a widespread disease that is extremely difficult to diagnose, especially in its early stages. About 6% to 8% of people over the age of 65 have Alzheimer's disease. At the beginning, the symptoms of this disease are relatively mild and are often misconstrued as ordinary signs of aging. As the disease progresses, symptoms increase from mild forgetfulness to severe disruption of all cognitive functions of the brain. However, a definitive diagnosis of Alzheimer's is currently possible only post-mortem by histopathological examination of brain tissue.
- the object of the invention is therefore to show a way how a physician early diagnosis of Alzheimer's can be facilitated.
- This object is achieved by a method for the spectroscopic examination of samples taken from human tissue or body fluids, in particular blood, comprising the following steps:
- a device for examining samples taken from human tissue or body fluids, in particular blood comprising: a light source for emitting infrared light, a spectrometer for measuring an infrared spectrum of a sample of the body fluid to be examined, an evaluation unit which, during operation, determines at least one sample parameter by evaluating the measured infrared spectrum, which determines the infrared spectrum in at least one of the following number of wavelengths
- 1034 cm “1 to 1074 cm “ 1 which compares at least one sample parameter with at least one reference parameter obtained by evaluating at least one reference spectrum measured on at least one sample of body fluid from patients suffering from Alzheimer's; Assign sample to a class with elevated Alzheimer's Disease, if the deviation of the at least one Parameters of the at least one reference parameter does not exceed a predetermined value.
- EP 0 644 412 A2 discloses a method for analyzing clinically relevant fluids with regard to liver cirrhosis or diabetes.
- the known method involves the following steps: a) Measurement of infrared spectra of a plurality of samples belonging to known classes, i.
- EP 0 644 412 A2 An overview of the use of infrared spectroscopic examinations in the field of medical diagnostics is provided by the article by W. Petrich in Applied Spectroscopy Reviews, 36 (2 & 3), 181-237 (2001). In the context of the present invention, it has been found that the method known from EP 0 644 412 A2 can also assist in the diagnosis of Alzheimer's disease by allowing samples of a class with an increased Alzheimer's suspicion to be assigned. With regard to the measuring technique and advantageously applicable multivariate evaluation method, reference is made to EP 0 644 412 A2, the disclosure of which is incorporated by reference into the subject of the present application.
- a sample of a class with an increased Alzheimer suspicion can be assigned with surprising reliability by determining a sample parameter which characterizes the infrared spectrum in at least one of the wave number ranges mentioned above.
- this sample parameter is obtained by a multivariate evaluation method, for example by discriminant analysis, cluster analysis or neural networks.
- the validity of the sample parameter is higher if several of the above wave number ranges, in particular the ranges of 1034 cm “1 to 1074 cm “ 1 , 1089 cm “ 1 to 1123 cm “ 1 and / or 2798 cm “1 to 2835 cm “ 1 in the evaluation is included so that the sample parameter characterizes the infrared spectrum in several wavenumber ranges.
- a sample spectrum can be represented by a point in a multidimensional parameter space.
- a reference spectrum as a point, or a group of reference spectra as a point cloud can be represented in the parameter space.
- the coordinates of the points characterizing the sample or reference spectra can be used as sample or reference parameters are understood.
- the assignment of the sample to a class with an increased Alzheimer's suspicion can be based on the distance between points representing sample or reference spectra.
- the assignment can also take place by means of a neural network and it can only be ascertained that the corresponding spectra in the one or more spectral regions relevant to the invention are sufficiently similar for an assignment.
- the threshold value for the deviation of the sample parameter from the reference parameter is not given as an absolute value, but depends on the result of a comparison of the sample parameter with a second reference parameter.
- the second reference parameter characterizes spectra measured on samples from persons in a comparison group.
- this comparison group can be people who are healthy.
- the persons of the comparison group suffer from a dementia disease different from Alzheimer's, for example a vascular dementia. The symptoms of various dementias are often very similar, so that diagnosis can be very difficult even for experienced physicians.
- Difficult is often the distinction between Alzheimer's and other perceptive or memory disorders as well as mental illnesses, especially depression. Such diseases are in the English-language literature under the term “cognitive impairment” summarized.
- FIG. 1 shows an absorption spectrum of a blood sample of an Alzheimer's patient.
- Figure 1 shows in the upper third of a typical absorption spectrum, which was measured on a dried sample blood serum of a patient with Alzheimer's disease. The intensity is plotted in arbitrary units over the wavenumber in cm -1 . Wavelength ranges which are particularly significant for the assignment of the sample to a class with an increased Alzheimer suspicion are indicated by solid bars in Figure 1. These particularly important wavenumber ranges are: 1034 cm -1. 1 to 1074 cm “1 , 1089 cm “ 1 to 1123 cm “ 1 , 1338 cm “ 1 to 1364 cm “ 1 , 1429 cm” 1 to 1475 cm “1 , 1723 cm “ 1 to 1733 cm “1 , 2798 cm “ 1 to 2835 cm “1 and 2850 cm” 1 to 2886 cm “1 .
- a sample parameter was determined which characterizes the sample spectrum shown in the wavenumber range mentioned above. To decide whether to assign this sample to a class with elevated Alzheimer's Disease is, the sample parameter is compared with a reference parameter.
- the reference parameter characterizes in the wavenumber ranges mentioned reference spectra measured on samples of the body fluid of patients suffering from Alzheimer's.
- the reference parameter is determined as well as the sample parameter by using a multivariate evaluation method.
- reference spectra it is possible initially to determine a reference parameter separately for each reference spectrum and to determine the sample parameter with a value derived from the individual reference parameters, e.g. the mean, to compare. Another possibility is to determine from a plurality of measured reference spectra for the wave number ranges mentioned a characteristic general reference spectrum for which a single reference parameter is determined for comparison with the sample parameter.
- the sample is assigned to a class with an increased Alzheimer suspicion.
- the Mann-Whitney score is plotted in FIG. 1 for the respective wavenumber of the spectrum.
- the Mann-Whitney Score is a measure of the reliability of assigning the sample to a class of elevated Alzheimer's Disease, based solely on the respective wave number.
- the Mann-Whitney score indicates how characteristic the intensity of a spectrum is at a given wave number for Alzheimer's disease. As you can see, the Mann-Whitney score shows no strongly pronounced maxima, so that a reliable assignment of a sample spectrum to a class with increased Alzheimer suspicion at first sight seems hopeless.
- wavenumber ranges are marked by black bars which, when the multivariate is indicated by its abbreviation, is used
- the multivariate evaluation methods used are linear discriminant analysis LDA, robust linear discriminant analysis R-LDA, support vector machines SVM and neural networks ANN.
- LDA linear discriminant analysis
- R-LDA robust linear discriminant analysis
- SVM support vector machines
- ANN neural networks
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Medical Informatics (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Pathology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Physics & Mathematics (AREA)
- Physiology (AREA)
- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Developmental Disabilities (AREA)
- Computer Vision & Pattern Recognition (AREA)
- Primary Health Care (AREA)
- Epidemiology (AREA)
- Signal Processing (AREA)
- Neurosurgery (AREA)
- Artificial Intelligence (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Data Mining & Analysis (AREA)
- Databases & Information Systems (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP05803953A EP1842047A1 (de) | 2004-12-18 | 2005-11-12 | Verfahren und vorrichtung zur spektroskopischen untersuchung von k\rperfl]ssigkeiten und gewebeproben hinsichtlich eines erh\hten alzheimerverdachts |
US11/762,978 US20080036999A1 (en) | 2004-12-18 | 2007-06-14 | Spectroscopic examination of body fluid and tissue samples to aid diagnosis of alzheimer's disease |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102004061064A DE102004061064A1 (de) | 2004-12-18 | 2004-12-18 | Verfahren und Vorrichtung zur spektroskopischen Untersuchung von Körperflüssigkeiten und Gewebeproben hinsichtlich eines erhöhten Alzheimerverdachts |
DE102004061064.9 | 2004-12-18 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/762,978 Continuation US20080036999A1 (en) | 2004-12-18 | 2007-06-14 | Spectroscopic examination of body fluid and tissue samples to aid diagnosis of alzheimer's disease |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006063644A1 true WO2006063644A1 (de) | 2006-06-22 |
Family
ID=35788017
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2005/012151 WO2006063644A1 (de) | 2004-12-18 | 2005-11-12 | Verfahren und vorrichtung zur spektroskopischen untersuchung von körperflüssigkeiten und gewebeproben hinsichtlich eines erhöhten alzheimerverdachts |
Country Status (4)
Country | Link |
---|---|
US (1) | US20080036999A1 (de) |
EP (1) | EP1842047A1 (de) |
DE (1) | DE102004061064A1 (de) |
WO (1) | WO2006063644A1 (de) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1853894A1 (de) * | 2005-02-22 | 2007-11-14 | McGill University | Vorrichtung zur messung von oxidativem stress sowie damit verbundene verfahren |
CN101949834A (zh) * | 2010-08-02 | 2011-01-19 | 扬州福尔喜果蔬汁机械有限公司 | 水果内部品质检测分级方法 |
EP2700933A1 (de) * | 2012-08-20 | 2014-02-26 | Consejo Superior De Investigaciones Científicas (CSIC) | Raman-, Infrarot- oder Raman-Infrarot-Analyse der peripheren Blutplasmaproteinstruktur und deren Beziehung zur kognitiven Entwicklung von Morbus Alzheimer |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2396106B1 (es) * | 2011-08-08 | 2014-06-06 | Consejo Superior De Investigaciones Científicas (Csic) | Análisis infrarrojo de fracciones de sangre periférica obtenida para indicar desarrollo cognitivo asociado a la enfermedad de alzheimer. |
CN104374739A (zh) * | 2014-10-30 | 2015-02-25 | 中国科学院半导体研究所 | 一种基于近红外定性分析的种子品种真实性鉴别方法 |
WO2018085699A1 (en) * | 2016-11-04 | 2018-05-11 | Nueon Inc. | Combination blood lancet and analyzer |
CN109658583A (zh) * | 2019-02-01 | 2019-04-19 | 广东工业大学 | 基于太赫兹光谱的发票鉴别方法、装置、设备及存储介质 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5267151A (en) * | 1990-09-07 | 1993-11-30 | Ham Frederic M | Method and apparatus for detecting and identifying a condition |
EP0644412A2 (de) * | 1993-09-17 | 1995-03-22 | Roche Diagnostics GmbH | Verfahren zur Analyse klinisch relevanter Flüssigkeiten und Suspensionen |
DE19649971A1 (de) * | 1996-11-19 | 1998-05-28 | Diagnostikforschung Inst | Optische Diagnostika zur Diagnostik neurodegenerativer Krankheiten mittels Nahinfrarot-Strahlung (NIR-Strahlung) |
US20040092027A1 (en) * | 2001-01-22 | 2004-05-13 | Andreas Wolf | Rapid test for biological substances using ftir |
US6777241B1 (en) * | 1999-05-20 | 2004-08-17 | Robert-Koch-Institut | Method for diagnosing TSE-induced changes in tissues using infrared spectroscopy |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4331596A1 (de) * | 1993-09-17 | 1995-03-23 | Boehringer Mannheim Gmbh | Verfahren zur quantitativen Analyse von Probenflüssigkeiten |
-
2004
- 2004-12-18 DE DE102004061064A patent/DE102004061064A1/de not_active Withdrawn
-
2005
- 2005-11-12 EP EP05803953A patent/EP1842047A1/de not_active Withdrawn
- 2005-11-12 WO PCT/EP2005/012151 patent/WO2006063644A1/de active Application Filing
-
2007
- 2007-06-14 US US11/762,978 patent/US20080036999A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5267151A (en) * | 1990-09-07 | 1993-11-30 | Ham Frederic M | Method and apparatus for detecting and identifying a condition |
EP0644412A2 (de) * | 1993-09-17 | 1995-03-22 | Roche Diagnostics GmbH | Verfahren zur Analyse klinisch relevanter Flüssigkeiten und Suspensionen |
DE19649971A1 (de) * | 1996-11-19 | 1998-05-28 | Diagnostikforschung Inst | Optische Diagnostika zur Diagnostik neurodegenerativer Krankheiten mittels Nahinfrarot-Strahlung (NIR-Strahlung) |
US6777241B1 (en) * | 1999-05-20 | 2004-08-17 | Robert-Koch-Institut | Method for diagnosing TSE-induced changes in tissues using infrared spectroscopy |
US20040092027A1 (en) * | 2001-01-22 | 2004-05-13 | Andreas Wolf | Rapid test for biological substances using ftir |
Non-Patent Citations (1)
Title |
---|
KIM H T ET AL: "Computerized recognition of Alzheimer disease-EEG using genetic algorithms and neural network", FUTURE GENERATIONS COMPUTER SYSTEMS, ELSEVIER SCIENCE PUBLISHERS. AMSTERDAM, NL, vol. 21, no. 7, July 2005 (2005-07-01), pages 1124 - 1130, XP004923792, ISSN: 0167-739X * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1853894A1 (de) * | 2005-02-22 | 2007-11-14 | McGill University | Vorrichtung zur messung von oxidativem stress sowie damit verbundene verfahren |
CN101949834A (zh) * | 2010-08-02 | 2011-01-19 | 扬州福尔喜果蔬汁机械有限公司 | 水果内部品质检测分级方法 |
EP2700933A1 (de) * | 2012-08-20 | 2014-02-26 | Consejo Superior De Investigaciones Científicas (CSIC) | Raman-, Infrarot- oder Raman-Infrarot-Analyse der peripheren Blutplasmaproteinstruktur und deren Beziehung zur kognitiven Entwicklung von Morbus Alzheimer |
WO2014029767A1 (en) * | 2012-08-20 | 2014-02-27 | Consejo Superior De Investigaciones Científicas C.S.I.C. | Raman, infrared, or raman-infrared analysis of peripheral blood plasma protein structure and its relation to cognitive development in alzheimer's disease |
CN104813159A (zh) * | 2012-08-20 | 2015-07-29 | 高级科学研究委员会C.S.I.C. | 外周血血浆蛋白质结构的拉曼、红外或拉曼-红外分析及其与阿尔茨海默氏症的认知发育的关系 |
AU2013305058B2 (en) * | 2012-08-20 | 2017-10-26 | Consejo Superior De Investigaciones Científicas C.S.I.C. | Raman, infrared, or Raman-infrared analysis of peripheral blood plasma protein structure and its relation to cognitive development in Alzheimer's disease |
Also Published As
Publication number | Publication date |
---|---|
DE102004061064A1 (de) | 2006-06-29 |
US20080036999A1 (en) | 2008-02-14 |
EP1842047A1 (de) | 2007-10-10 |
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