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 suggest that compensatory processes associated with graceful aging are not necessarily a sign of early saturation of executive resources, if this saturation was to be represented by a systematic frontal hyperactivation. The role of the PFC over-recruitment and age-related neurofunctional changes in healthy olders was further investigated in Chapter 4. In particular in this study we reviewed the neurofunctional data collected in the third Chapter in the light of the HAROLD model (Hemispheric Asymmetry Reduction in Olders). Again, the data clearly suggested that the manifestation of age-related neurofunctional changes of functional lateralization in healthy olders is not exclusively restricted to the frontal areas, rather these are distributed across the entire brain volume in a task-related manner. Finally, in order to better address neurofunctional and neuroanatomical changes in pathological aging and to create a link with theoretical frameworks that describe graceful aging, we compared behavioural, neurofunctional and neuroanatomical data of 24 healthy olders and 9 aMCI patients, challenged with the same lexical-semantic and episodic long-term memory tasks used in Chapter 3. The between groups differences were analysed in the light of our previous findings on the neural pattern of compensatory processes in healthy aging (described in Chapter 3). A systematic pattern emerged: aMCI patients showed over-activations in parts of the task-specific neural networks that are dysfunctional in highly-performing healthy olders, while they under-recruited the task-specific compensatory neural networks typically over-activated by healthy older controls. Moreover, the over-recruitments of areas which became of no use in healthy aging showed a negative correlation with the gray matter density in the medial temporal lobe structures. These results are discussed in terms of lack of neural plasticity in pathological aging. I conclude my dissertation with chapter 6 where I propose a neurocognitive account of healthy and pathological aging in terms of compensatory processes and neural plasticity.