Prodromal stages of neurodegenerative diseases: proposals for new approaches in diagnosis and intervention.

As life expectancy is increasing, new ways to maintain a good quality of life and to prevent neurodegenerative diseases are fundamental. In Study 1, we aimed at investigating both behavioral and neurofunctional effects of a 5-weeks treatment for patients with single and multiple-domain aMCI. There is evidence that non-specific domain trainings might be beneficial for patients with MCI, and a non-invasive modulation technique, Prismatic Adaptation (PA), seems to entail a diffuse effect on higher cognition as well. Thus, we implemented a digital treatment involving the use of PA combined with Serious Games. To date, we have recruited 10 patients, who underwent neuropsychological assessments and resting-state fMRI exams, before and after the treatment. They were divided into two groups, one who received PA with real lenses (experimental), and the other who received PA with neutral lenses (control). Our results suggest that the 5-weeks treatment was beneficial in preventing cognitive deterioration in that timeframe, and in sustaining attention, in both groups. We also observed an increased anti-correlation between the Default Mode Network (DMN) and the Dorsal Attention Network (DAN) during resting-state in the experimental group after the treatment. This result is in line with current literature, and it also reflects the potential neurofunctional effects of PA. Study 2.1 and 2.2 focus on the attention capabilities of healthy elderlies and their differences from aMCI patients. In Study 2.1 we explored the characteristics of attentional subcomponents, namely alerting, orienting, and executive control, in healthy individuals older than 65 years old, and investigated whether PA could modulate them. To do so, we recruited 20 participants and administered them with the Attention Network Test (ANT) before and after one single session of PA. Results suggest that only the alerting component was modulated by PA. In Study 2.2 we compared the performances at ANT of the healthy participants matched with the aMCI patients of Study 1. We found patients being significantly more slowly and less accurate than healthy elderlies. Finally, the Study 3 presents a single case of unilateral right tactile agnosia, in the context of a rare neurodegenerative disease, namely Cortical Basal Syndrome (CBS). The patient, a 55-year-old woman, initially presented with a left frontoparietal atrophy and the outcome of the surgical removal of a right parietal oligodendroglioma. She referred difficulties in haptic object recognition and in right-hand sensitivity. We performed an experimental evaluation of somatosensory functions and tactile agnosia, targeting every level of tactile processing. We recruited 18 healthy controls age- and education-matched. Furthermore, we followed the patient’s clinical evolution for three years. The initial neuropsychological assessment revealed only apraxia for the right hand. The patient showed normal tactile sensitivity and she was accurate for most hylognosis functions. Conversely, she was impaired with the right hand in meaningless-shapes test. Three years after symptoms onset, a DaTSCAN, previously negative, became positive. The MR showed a progression of the left frontoparietal atrophy in the absence of a tumoral relapse. Behaviourally, apraxia and morphoagnosia appeared also in the left hand. The patient's clinical profile is consistent with the diagnosis of CBS and unilateral tactile agnosia as the primary symptom onset. This is the third case described in the literature manifesting morphoagnosia without hyloagnosia and the first description of such dissociation in a case with CBS. Overall, our studies demonstrate that the understanding of physiological changes in the elderly needs further exploration. Such knowledge can be indispensable for early diagnoses and for the development of treatments, both in the context of most common conditions, e.g., MCI, and even in rare neurodegenerative diseases, e.g., CBS.