. The First Key Symposium was held in Stockholm, Sweden, 2–5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 +/- 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) after 2.0 +/- 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-d-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test-retest). Relative PIB retention in cortical regions differed by 3-7% in the test-retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 +/- 3.7 (mean +/- standard deviation) to 22.7 +/- 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 +/- 3.5 to 15.6 +/- 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 +/- 3.1 to 25.9 +/- 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.

The accumulation of pathological misfolded tau is a feature common to a collective of neurodegenerative disorders known as tauopathies, of which Alzheimer's disease (AD) is the most common. Related tauopathies include progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), Down's syndrome (DS), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Investigation of the role of tau pathology in the onset and progression of these disorders is now possible due the recent advent of tau-specific ligands for use with positron emission tomography (PET), including first-(e.g., [ 18 F] THK5317, [ 18 F]THK5351, [ 18 F]AV1451, and [ 11 C]PBB3) and second-generation compounds [namely [ 18 F]MK-6240, [ 18 F] RO-948 (previously referred to as [ 18 F]RO69558948), [ 18 F]PI-2620, [ 18 F]GTP1, [ 18 F]PM-PBB3, and [ 18 F]JNJ64349311 ([ 18 F]JNJ311) and its derivative [ 18 F]JNJ-067)]. In this review we describe and discuss findings from in vitro and in vivo studies using both initial and new tau ligands, including their relation to biomarkers for amyloid-β and neurodegeneration, and cognitive findings. Lastly, methodological considerations for the quantification of in vivo ligand binding are addressed, along with potential future applications of tau PET, including therapeutic trials.

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See Schott and Fox (doi: ) for a scientific commentary on this article. The relationships between pathophysiological processes in Alzheimer’s disease remain largely unclear. In a longitudinal, multitracer PET study, Rodriguez-Vieitez et al. reveal that progression of autosomal dominant Alzheimer’s disease is accompanied by prominent early and then declining astrocytosis, increasing amyloid plaque deposition and decreasing glucose metabolism. Astrocyte activation may initiate Alzheimer pathology.

The objective of this study was to assess whether reduced glucose metabolism (rCMRGlu) and cognitive functioning could predict development of Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Twenty MCI patients underwent baseline and follow-up investigations of rCMRGlu, as measured by PET, and cognitive function measured by neuropsychological test assessments. Subjects were clinically followed up with an average interval of 36.5 months. Two groups were obtained after the second clinical assessment. Nine patients were diagnosed as AD and classified as progressive MCI (P-MCI), whereas 11 patients remained clinically stable and were classified as stable MCI (S-MCI). There were no differences in demographic variables or baseline MMSE between the two subgroups. Logistic regression indicated the two variables that most effectively predicted future development of AD were rCMRGlu from the left temporoparietal area and performance on the block design. These combined measures gave an optimal 90% correct classification rate, whereas only rCMRGlu or neuropsychology alone gave 75% and 65% correct classification, respectively. Measures of temporoparietal cerebral metabolism and visuospatial function may aid in predicting the evolution to AD for patients with MCI.