Implication of Cognitive Reserve in Non-pharmacological Intervention Outcomes

Cognitive reserve (CR) is defined as the gradual accumulation of neural resources and their adaptability (i.e., efficiency, capacity, flexibility) due to genetic and/or lifelong environmental factors that mitigate the cognitive effects of age-related processes and brain diseases. Transcranial alternating current stimulation (tACS) can be used to entrain underlying neuronal networks, promoting firing at specific frequencies. Recent studies have demonstrated that fronto-parietal theta oscillatory activity entrainment via tACS leads to working memory enhancement in healthy subjects. However, there remains significant variability in stimulation-induced aftereffects across individuals. Emerging literature suggests that individual differences, such as CR levels, may be crucial in predicting the benefits of treatment interventions, as they reflect available neural capacity and flexibility. A novel interventional approach is proposed to study CR, utilizing both conventional static proxies, such as premorbid intellect and educational attainment, and dynamic markers, including pupillometry, resting-state, and task-induced functional MRI. By employing cutting-edge noninvasive brain stimulation (NIBS) techniques, the study will acutely modulate network properties to examine the influence of CR on immediate cognitive and brain functional aftereffects induced by the intervention. In addition to focusing on cognitively healthy older adults, this study will, for the first time, include patients with mild cognitive impairment with Lewy bodies (MCI-LB), a prodromal stage of the second most common degenerative dementia after Alzheimer's disease.

Inclusion Criteria: * Intact cognitive performance as assessed by cognitive evaluation. * Subjects with possible or probable mild cognitive impairment with Lewy bodies (MCI-LB). Exclusion Criteria: * Presence of dementia as assessed by a cognitive test battery and evaluation of daily activities. * Any major psychiatric disorder. * History of neurological disease affecting the central nervous system (e.g., tumor, epilepsy, stroke, etc.). * Severe or repeated head injury. * Non-compensated internal or oncological disease. MRI-incompatible metal in the body (e.g., pacemaker). Left-handedness.