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We used principal component analysis to decompose functional images of patients with AD in orthogonal ensembles of brain regions with maximal metabolic covariance. Three principal components explained 38% of the total variance in a large sample of FDG-PET images obtained in 225 AD patients. One functional ensemble (PC2) included limbic structures from Papez's circuit (medial temporal regions, posterior and anterior cingulate cortex, thalamus); its disruption in AD patients was related to episodic memory impairment. Another principal component (PC1) illustrated major metabolic variance in posterior cerebral cortices, and patients' scores were correlated to instrumental functions (language and visuospatial abilities). PC3 comprised frontal, parietal, temporal and posteromedial (posterior cingulate and precuneus) cortices, and patients' scores were related to executive dysfunction and global cognitive impairment. The three main metabolic covariance networks converged in the posterior cingulate area that showed complex relationships with medial temporal structures within each PC. Individual AD scores were distributed as a continuum along PC axes: an individual combination of scores would determine specific clinical symptoms in each patient

Statistical parametric mapping (SPM) for the in-vivo assessment of brain functional parameters in neurological diseases is a voxel-based methodology used within the nuclear medicine community to increase the confidence level of diagnostic reporting. SPECT/PET SPM measurements result in maps of statistically significant hypo-/ hyperfunctionality in cerebral regions of the patient with respect to normal controls [1]. In general, voxel-based assessments of changes in the functional signal allow earlier and better diagnosis of neurological pathologies, which are also less biased than qualitative visual inspection of images or quantitative region-of-interest analysis

There is a considerable body of neuropsychological and neuroimaging evidence supporting the distinction between the brain correlates of noun and verb processing. It is however still not clear whether the observed differences are imputable to grammatical or semantic factors. Beyond the basic difference that verbs typically refer to actions and nouns typically refer to objects, other semantic distinctions might play a role as organizing principles within and across word classes. One possible candidate is the notion of manipulation and manipulability, which may modulate the word class dissociation. We used functional magnetic resonance imaging (fMRI) to study the impact of semantic reference and word class on brain activity during a picture naming task. Participants named pictures of objects and actions that did or did not involve manipulation. We observed extensive differences in activation associated with the manipulation dimension. In the case of manipulable items, for both nouns and verbs, there were significant activations within a fronto-parietal system subserving hand action representation. However, we found no significant effect of word class when all verbs were compared to all nouns. These results highlight the impact of the biologically crucial sensorimotor dimension of manipulability on the pattern of brain activity associated to picture naming.

OBJECTIVES: To investigate whether the combination of fluoro-2-deoxy-d-glucose (FDG) PET measures with the APOE genotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHOD: After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in baseline regional glucose metabolic rate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (converters [n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [n = 16] vs noncarriers [E4-] [n = 21]) as grouping factors. Results were considered significant at p < 0.05, corrected for multiple comparisons. RESULTS: All converters showed reduced rCMRglc in the inferior parietal cortex (IPC) as compared with the nonconverters. Hypometabolism in AD-typical regions, that is, temporoparietal and posterior cingulate cortex, was found for the E4+ as compared with the E4- patients, with the E4+/converters (n = 5) having additional rCMRglc reductions within frontal areas, such as the anterior cingulate (ACC) and inferior frontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion to AD with 84% overall diagnostic accuracy (p = 0.003). Moreover, ACC and IFC rCMRglc improved prediction for the E4+ group, yielding 100% sensitivity, 90% specificity, and 94% accuracy (p < 0.0005), thus leading to an excellent discrimination. CONCLUSION: Fluoro-2-deoxy-d-glucose-PET measures may improve prediction of the conversion to Alzheimer disease, especially in combination with the APOE genotype.

The existence of a "critical period" for language acquisition is controversial. Bilingual subjects with variable age of acquisition (AOA) and proficiency level (PL) constitute a suitable model to study this issue. We used functional magnetic resonance imaging to investigate the effects of AOA and PL on neural correlates of grammatical and semantic judgments in Italian-German bilinguals who learned the second language at different ages and had different proficiency levels. While the pattern of brain activity for semantic judgment was largely dependent on PL, AOA mainly affected the cortical representation of grammatical processes. These findings support the view that both AOA and PL affect the neural substrates of second language processing, with a differential effect on grammar and semantics.