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The measurement of hyperphosphorylated tau (p-tau) in CSF has been proposed as a biomarker candidate for the prediction of Alzheimer disease (AD) in patients with mild cognitive impairment (MCI). However, a standard quantitative criterion of p-tau has not been evaluated.

Cognitive function requires a high level of functional interaction between regions of a network supporting cognition. Assuming that brain activation changes denote an advanced state of disease progression, changes in functional connectivity may precede changes in brain activation. The objective of this study was to investigate changes in functional connectivity of the right middle fusiform gyrus (FG) in subjects with mild cognitive impairment (MCI) during performance of a face-matching task. The right middle FG is a key area for processing face stimuli. Brain activity was measured using functional MRI. There were 16 MCI subjects and 19 age-matched healthy controls. The linear correlation coefficient was utilized as a measure of functional connectivity between the right middle FG and all other voxels in the brain. There were no statistical differences found in task performance or activation between groups. The right middle FG of the healthy control and MCI groups showed strong bilateral positive linear correlation with the visual cortex, inferior and superior parietal lobules, dorsolateral prefrontal cortex (DLPFC) and anterior cingulate. The healthy controls showed higher positive linear correlation of the right middle FG to the visual cortex, parietal lobes and right DLPFC than the MCI group, whereas the latter had higher positive linear correlation in the left cuneus. In the healthy controls, the right middle FG had negative linear correlation with right medial frontal gyrus and superior temporal gyrus and with left inferior parietal lobule (IPL), angular gyrus, superior frontal gyrus and anterior cingulate gyrus, but the MCI group had negative linear correlation with the left IPL, angular gyrus, precuneus, anterior cingulate, and to right middle temporal gyrus and posterior cingulate gyrus. In the negatively linearly correlated regions, the MCI group had reduced functional connectivity to the frontal areas, right superior temporal gyrus and left IPL. Different regions of the cuneus and IPL had increased functional connectivity in either group. The putative presence of Alzheimer's disease neuropathology in MCI affects functional connectivity from the right middle FG to the visual areas and medial frontal areas. In addition, higher linear correlation in the MCI group in the parietal lobe may indicate the initial appearance of compensatory processes. The results demonstrate that functional connectivity can be an effective marker for the detection of changes in brain function in MCI subjects.

Comparative study of CSF levels of tau and AD7C-neuronal thread protein (NTP) in patients with AD and control subjects.

To determine whether the size of the corpus callosum is related to the extent of white matter pathology in patients with AD and age-matched healthy control subjects.

Zusammenfassung: Die Magnetresonanztomographie (MRT) des Gehirns kommt als strukturelles bildgebendes Verfahren in der Psychiatrie und Neurologie zur breiten Anwendung. Bei der Demenz vom Alzheimer-Typ (AD) trägt die MRT zur Verbesserung der klinischen Diagnosestellung im Rahmen der Mehrebenendiagnostik [1] und zur differentialdiagnostischen Abgrenzung anderer mit einem dementiellen Syndrom einhergehender Erkrankungen bei. Neu entwickelte Verfahren der MRT-gestützten Volumetrie kortikaler und subkortikaler Strukturen erwiesen sich als nützlich in der Differenzierung zwischen kognitiv gesunden älteren Probanden und AD-Patienten. Darüber hinaus versprechen sie neue Einsichten in den zeitlichen und strukturellen Verlauf der zerebralen Degeneration. Zusätzlich kann die systematische quantitative Erfassung von Signalveränderungen bei AD-Patienten zur Verbesserung der diagnostischen Genauigkeit beitragen. Es ist die Absicht dieser Arbeit, den Beitrag der MRT zur Diagnostik der AD und zum Verständnis ihrer Pathogenese darzustellen, aber auch die Grenzen dieser Methodik aufzuzeigen. Dabei werden die Veränderungen des gesunden Alterungsprozesses miteinbezogen, die mit Hilfe der MRT-Bildgebung faßbar sind. Zukünftige Perspektiven liegen insbesondere in der Weiterentwicklung der mikroskopischen MRT, der genauen Differenzierung und Klassifikation von Signalveränderungen der weißen Substanz und im kombinierten Einsatz der MRT mit funktionellen bildgebenden Methoden.

In this longitudinal study of 77 patients with mild cognitive impairment (MCI), the authors analyzed whether levels of tau protein phosphorylated at threonine 231 (p-tau231) in CSF correlate with progression of cognitive decline. High CSF p-tau231levels at baseline, but not total tau protein levels, correlated with cognitive decline and conversion from MCI to AD. Independently, old age and APOE-4 carrier status were predictive as well. Our data indicate that an increased p-tau231level is a potential risk factor for cognitive decline in patients with MCI.