Abstract: The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/ cognitive outcomes. It has been suggested that the size of the brain (brain reserve) and the extent of neural connections acquired through life (neural reserve) set a threshold beyond which noticeable impairments occur. In contrast, cognitive reserve refers to the brain’s ability to adapt and reorganize structurally and functionally to resist damage and maintain function, including neural reserve and brain maintenance, resilience, and compensation (Verkhratsky and Zorec, 2024). We propose that noradrenergic regulation of astrocytes plays a key role in defining cognitive reserve. Astrocytes support neural homeostasis through multiple mechanisms and contribute to the pathogenesis of all neurological disorders (Verkhratsky et al., 2023). Astrocytes are key components in maintaining cognitive reserve; they contribute to shaping cytoarchitecture of the nervous tissue and synaptic transmission, thus supporting neural reserve and neural maintenance; astrocytes are central elements of brain defense and regeneration thus supporting brain resilience and compensation. We present an overview of the role of the noradrenergic innervation of astrocytes in both normal and neurodegenerative states, then we point out that the demise of the noradrenergic system is an early event in many, if not all neurodegenerative diseases, acting through astrocytes and limiting their support of cognitive reserve.