Improved connectivity and cognition due to cognitive stimulation in Alzheimer's disease.

Background: Due to the increasing prevalence of Alzheimer's disease (AD) and the limited efficacy of pharmacological treatment, the interest in non-pharmacological interventions, e.g., cognitive stimulation therapy (CST), to improve cognitive dysfunction and the quality of life of AD patients are on a steady rise. Objectives: Here, we examined the efficacy of a CST program specifically conceptualized for AD dementia patients and the neural mechanisms underlying cognitive or behavioral benefits of CST. Methods: Using neuropsychological tests and MRI-based measurements of functional connectivity, we examined the (neuro-) psychological status and network changes at two time points: pre vs. post-stimulation (8 to 12 weeks) in the intervention group (n = 15) who received the CST versus a no-intervention control group (n = 15). Results: After CST, we observed significant improvement in the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale, cognitive subsection (ADAS-cog), and the behavioral and psychological symptoms of dementia (BPSD) scores. These cognitive improvements were associated with an up-regulated functional connectivity between the left posterior hippocampus and the trunk of the left postcentral gyrus. Conclusion: Our data indicate that CST seems to induce short-term global cognition and behavior improvements in mild to moderate AD dementia and enhances resting-state functional connectivity in learning- and memory-associated brain regions. These convergent results prove that even in mild to moderate dementia AD, neuroplasticity can be harnessed to alleviate cognitive impairment with CST.

Graph Theory Analysis Reveals Resting-State Compensatory Mechanisms in Healthy Aging and Prodromal Alzheimer's Disease.

Several theories of cognitive compensation have been suggested to explain sustained cognitive abilities in healthy brain aging and early neurodegenerative processes. The growing number of studies investigating various aspects of task-based compensation in these conditions is contrasted by the shortage of data about resting-state compensatory mechanisms. Using our proposed criterion-based framework for compensation, we investigated 45 participants in three groups: (i) patients with mild cognitive impairment (MCI) and positive biomarkers indicative of Alzheimer's disease (AD); (ii) cognitively normal young adults; (iii) cognitively normal older adults. To increase reliability, three sessions of resting-state functional magnetic resonance imaging for each participant were performed on different days (135 scans in total). To elucidate the dimensions and dynamics of resting-state compensatory mechanisms, we used graph theory analysis along with volumetric analysis. Graph theory analysis was applied based on the Brainnetome atlas, which provides a connectivity-based parcellation framework. Comprehensive neuropsychological examinations including the Rey Auditory Verbal Learning Test (RAVLT) and the Trail Making Test (TMT) were performed, to relate graph measures of compensatory nodes to cognition. To avoid false-positive findings, results were corrected for multiple comparisons. First, we observed an increase of degree centrality in cognition related brain regions of the middle frontal gyrus, precentral gyrus and superior parietal lobe despite local atrophy in MCI and healthy aging, indicating a resting-state connectivity increase with positive biomarkers. When relating the degree centrality measures to cognitive performance, we observed that greater connectivity led to better RAVLT and TMT scores in MCI and, hence, might constitute a compensatory mechanism. The detection and improved understanding of the compensatory dynamics in healthy aging and prodromal AD is mandatory for implementing and tailoring preventive interventions aiming at preserved overall cognitive functioning and delayed clinical onset of dementia.