Correlation between Cognitive Impairment and CSF Biomarkers in Amnesic MCI, non-Amnesic MCI, and Alzheimer's Disease

Contains fulltext : 90105.pdf (publisher's version ) (Open Access)Decreased delayed recall, decreased amyloid-beta peptides (A beta(1-42)), and increased tau protein concentration in cerebrospinal fluid (CSF) are generally regarded to be valid neuropsychological and biological markers for Alzheimer's disease (AD). Previous studies failed to demonstrate clear-cut correlations between neuropsychological impairment and CSF markers. In this study we test recent models of disease progression, that propose that changes in CSF biomarkers already reach a plateau in a preclinical phase, before cognitive decline begins, that is, even before MCI can be diagnosed. We recruited 73 patients with probable AD (n = 36) and mild cognitive impairment (MCI) (amnesic MCI = 25; non-amnesic MCI = 12). We used the CERAD-NP, a widely used neuropsychological battery with norms for different age and education groups, and additional neuropsychological tests for assessing the cognitive profile of these patient groups. We found a significant correlation between A beta(1-42) in the CSF and memory performance for amnesic MCI patients, but not for non-amnesic MCI and AD patients. All other correlations between cognitive tasks and A beta(1-42) were not significant. Tau protein concentration in the CSF was not correlated with any neuropsychological marker in any of the patients groups. We conclude that the decrease of A beta(1-42) in the CSF mirrors disease progression during the early stages up into AD and therefore is not restricted to the preclinical phase. The decrease of A beta(1-42) reaches a plateau only in the full blown demented syndrome and further functional disease progression is then related to neurodegeneration without further reduction of A beta(1-42) in the CSF

False recognition correlates with Beta-Amyloid (1-42), but not with total Tau in CSF of patients with dementia and mild cognitive impairment

Contains fulltext : 77085.pdf (publisher's version ) (Open Access)Severe memory impairment forms the core symptom of Alzheimer's disease (AD), which is present early in the disease course. Recent studies show that AD patients not only suffer from forgetfulness, but also differ in their response bias, when having to decide whether information has been perceived recently, or whether it is only familiar or semantically related to perceived information. Changes in total tau-protein and amyloid-β (Aβ)_{1-42} concentration in cerebrospinal fluid are also features of AD, and they predict conversion from mild cognitive impairment to dementia. In this study we correlated recognition scores with total tau and Aβ_{1-42} concentrations in patients with suggested dementia. We studied 40 patients and 21 healthy controls, using an incidental recognition memory task and a neuropsychological test battery. False recognition scores correlated with delayed recall and with Aβ_{1-42}, and Aβ_{1-42} tended to correlate with delayed recall. Total tau, however, did not correlate with memory scores or with neuropsychological performance in general. We suggest that Aβ_{1-42} may indicate a reduction in the specificity of the neuronal response in the limbic cortex, due to agglomeration of plaques. This process might be more specific for AD than the increase of tau, and therefore it is stronger correlated with recognition errors.9 p

False Recognition Helps to Distinguish Patients with Alzheimer's Disease and Amnestic MCI from Patients with Other Kinds of Dementia

Item does not contain fulltextTwo recent reviews on neuropsychological assessment argue that Alzheimer's disease (AD) is characterized by deficits in delayed recall and that this allows differentiating AD from other types of dementia. We attempted to differentiate patients with AD and amnestic mild cognitive impairment (MCI) from patients with fronto-subcortical dementia, normal pressure hydrocephalus and vascular dementia using a simple picture recognition task. We examined 130 patients, 89 with dementia and 41 with MCI. The combination of the CERAD-NP savings score and the number of false recognitions yielded a sensitivity of 100% for identifying AD patients. Moreover, adding the score for false recognitions to that of delayed recall improved the specificity of the diagnosis from 50% to 90%. After matching the groups on memory performance, the AD group still produced more false recognitions. The results suggest that delayed recall impairment and recognition errors stem from different sources. We also found that the number of false recognitions differs between amnestic and non-amnestic MCI patients. The quality of the differential diagnosis may therefore be enhanced significantly by taking into account both delayed recall and false recognitions provoked by a picture recognition task.9 p

Entwicklung von whisker- und kurzfaserverstaerkten Verbundwerkstoffen mit oxidkeramischer Matrix Abschlussbericht

Available from TIB Hannover: F97B503 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Dementia screening, biomarkers and protein misfolding: Implications for public health and diagnosis

Misfolded proteins are at the core of many neurodegenerative diseases, nearly all of them associated with cognitive impairment. For example, Creutzfeldt-Jacob disease is associated with aggregation of prion protein,1,2 Lewy body dementia and Parkinson disease with α-synuclein3,4 and forms of frontotemporal dementia with tau, TDP43 and a host of other proteins.5,6 Alzheimer disease (AD), the most common cause of dementia,7 and its prodromal syndrome mild cognitive impairment (MCI)8 are an increasing public health problem and a diagnostic challenge to many clinicians. AD is characterized pathologically by the accumulation of amyloid β-protein (Aβ)9,10 as senile plaques and in the walls of blood vessels as amyloid angiopathy.11,12 Additionally, there are accumulations of tau-protein as neurofibrillary tangles and dystrophic neurites.11,12 Biological markers of AD and MCI can serve as in vivo diagnostic indicators of underlying pathology, particularly when clinical symptoms are mild13–15 and are likely present years before the onset of clinical symptoms.16–19 Research to discover and refine fluid and imaging biomarkers of protein aggregation has undergone a rapid evolution20–22 and combined analysis of different modalities may further increase diagnostic sensitivity and specificity.23–26 Multi-center trials are now investigating whether imaging and/or cerebrospinal fluid (CSF) biomarker candidates can be used as outcome measures for use in phase III clinical trials for AD.27–2