The assessment of consciousness has been shaped largely by research on acquired disorders of consciousness after acute or chronic brain injury, but similar problems of unreliable behavioral expression increasingly arise in neurodegenerative disease. This translational overlap is especially relevant when preserved cognition, awareness, or intentionality cannot be reliably expressed because of severe motor impairment, fluctuating arousal, cognitive decline, aphasia, apraxia, or impaired cooperation. In neurodegenerative disease, degeneration of arousal systems, large-scale brain networks, cognition, and motor pathways may similarly make observable behavior an unreliable measure of awareness. The challenge is not only to determine if a patient responds, but also to ask if residual awareness, intentionality, or covert cognition can still be detected through physiological signals. This review discusses how contemporary modalities reshape this assessment. Electroencephalography has moved from a descriptive measure of background activity to a bedside tool capable of probing event-related responses, network organization, and cortical complexity. Magnetic resonance methods reveal altered connectivity within thalamocortical and default mode network systems, while functional near-infrared spectroscopy adds a portable hemodynamic approach that may be repeated at the bedside and integrated with active paradigms. Brain–computer interfaces provide a translational step by converting neural responses into evidence of command following or, in selected patients, into communication, and artificial intelligence strengthens these approaches by extracting clinically meaningful patterns from complex neural and hemodynamic data. Additionally, autonomic measures, including heart rate variability and baroreflex indices, are considered as auxiliary physiological context for arousal and engagement, and not as direct markers of awareness. Because the most mature evidence for covert awareness and cognitive-motor dissociation comes from acquired disorders of consciousness, this review treats brain injury literature as a methodological foundation instead of as directly interchangeable evidence for neurodegenerative disease. It then examines how these approaches may be adapted to neurodegenerative contexts, especially ALS, severe dementia, Lewy body disease with fluctuating cognition, and conditions in which communication or motor output becomes unreliable.