Brain dynamics associated with graceful and pathological aging: new morphometric and fMRI evidence

In the last decade, graceful aging has often been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal olders to perform these tasks at a juvenile level, in spite of the natural cortical impoverishment. It remains to be established, however, whether the frontal hyperactivation is the only possible neurofunctional manifestation of compensatory processes in halthy aging. In this thesis I present a systematic investigation of this issue and related issues on pathological aging seen in MCI. I first re-assessed the results of 23 recent neuroimaging papers on normal aging using a quantitative meta-analytic approach that allowed us to distinguish between task-dependent and task-independent age-related hyperactivations in healthy olders (Chapter 2). In particular, task-independent hyperactivations emerged in the prefrontal cortex (PFC) in line with the results commonly described in international litterature, while task-dependent hyperactivations emerged in brain regions beyond the prefrontal areas. Further, we investigated more directly the existence of task-specific neurofunctional manifestations of compensatory processes in a new fMRI / VBM study (Chapter 3). In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy olders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations in the group of healthy olders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Moreover, only hypoactivations did systematically overlap with regional atrophy. On the basis of these results we sugge
La raccolta dei dati fMRI e VBM è avvenuta presso il reparto di Neuroradiologia dell'A.O. Niguarda Cà Granda di Milano.La raccolta dei dati neuropsicologici è avvenuta presso il Laboratorio di Neuropsicologia Cognitiva dell'A.O. Niguarda Cà Granda. Lo script utilizzato per eseguire la metanalisi quantitativa attraverso algoritmo di clusterizzazione gerarchica è stato sviluppato dalla Dot.ssa Cattineli sotto la supervisione del Prof. Borghese del Dipartimento di Informatica dell'Università degli Studi di Milano.
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Berlingeri
Berlingeri, M