Background and Objective: Mild cognitive impairment (MCI) patients with small vessel disease (SVD) are at high dementia risk. We tested the effects of cognitive rehabilitation in these patients using the Attention Process Training-II (APT-II) program in a single-blinded, randomized clinical trial. Methods: Patients were randomized to APT-II or standard care and evaluated at baseline, 6, and 12 months with functional, quality of life, cognitive tests, and resting state functional MRI (rsfMRI). Results: Forty-six patients were enrolled and 43 (mean±SD age 75.1±6.8) completed the study. No change was seen in functionality and quality of life between treated and non-treated patients. However, the Rey Auditory-Verbal Learning Test immediate recall showed a significant improvement in treated compared to non-treated group (change score 6 versus 12 months: 1.8±4.9 and –1.4±3.8, p = 0.021; baseline versus 12 months: 3.8±6.1 and 0.2±4.4, p = 0.032). A higher proportion of treated patients had stable/better evaluation compared to non-treated group on Visual search test (6 versus 12 months: 95% versus 71%, p = 0.038) and Rey–Osterrieth Complex Figure copy (6 versus 12 months: 95% versus 67%, p = 0.027). RsfMRI, performed in a subsample, showed that the difference between follow-up and baseline in synchronization of activity in cerebellar areas was significantly greater in treated than in non-treated patients. Conclusion: We were unable to show a significant effect in quality of life or functional status in treated patients with MCI and SVD. However, APT-II produces some beneficial effects in focused attention and working memory and seems to increase activity in brain circuits involved in cognitive processes.

Task- and stimulus-based neuroimaging studies have begun to unveil the central autonomic network which modulates autonomic nervous system activity. In the present study, we aimed to evaluate the central autonomic network without the bias constituted by the use of a task. Additionally, we assessed whether this circuitry presents signs of dysregulation in the early stages of Parkinson’s disease (PD), a condition which may be associated with dysautonomia. We combined heart-rate-variability based methods for time-varying assessments of the autonomic nervous system outflow with resting-state fMRI in 14 healthy controls and 14 de novo PD patients, evaluating the correlations between fMRI time-series and the instantaneous high-frequency component of the heart-rate-variability power spectrum, a marker of parasympathetic outflow. In control subjects, the high-frequency component of the heart-rate-variability power spectrum was significantly anti-correlated with fMRI time-series in several cortical, subcortical and brainstem regions. This complex central network was not detectable in PD patients. In between-group analysis, we found that in healthy controls the brain activation related to the high-frequency component of the heart-rate-variability power spectrum was significantly less than in PD patients in the mid and anterior cingulum, sensorimotor cortex and supplementary motor area, insula and temporal lobe, prefrontal cortex, hippocampus and in a region encompassing posterior cingulum, precuneus and parieto-occipital cortex. Our results indicate that the complex central network which modulates parasympathetic outflow in the resting state is impaired in the early clinical stages of PD.