"Schrödinger's Rat": Testing Consciousness Under Anesthesia Alters Brain State and Neuronal Responses in Auditory Cortex.

Dementia is a leading cause of disability and dependency in ageing societies, and the number of affected individuals is projected to rise markedly by 2050 (). In the absence of curative therapies, increasing emphasis has been placed on prevention-oriented strategies that identify individuals at elevated risk as early as possible (, , ). Although biomarker-based frameworks have substantially advanced the biological characterization of Alzheimer’s disease across its continuum (; , ; ; ), access to biomarker testing remains uneven in routine clinical care and population settings (). Scalable, low-cost clinical signals that can be captured reliably in community and primary-care contexts are therefore needed to detect early neurocognitive vulnerability and support timely cognitive evaluation and prevention-oriented intervention (, , ). Instrumental activities of daily living (IADLs) reflect complex, cognitively mediated activities necessary for independent living, such as managing medications and finances, shopping, and meal preparation (). These tasks rely heavily on episodic memory, attention, and executive control, suggesting that subtle IADL difficulties may emerge during prodromal stages while basic self-care remains preserved. Accumulating evidence has challenged the traditional notion that mild cognitive impairment (MCI) is entirely functionally intact (; ; ). A systematic review reported consistent IADL vulnerabilities in MCI (), and longitudinal studies have shown that functional deficits in MCI predict progression to dementia (; ). Community- and clinic-based studies further suggest that cognitively demanding IADL impairments can discriminate early cognitive vulnerability from normal ageing (; ) and that specific Functional Activities Questionnaire items predict progression from clinically normal status to MCI (; ). Biological plausibility also supports this link: IADL impairment has been associated with amyloid and tau burden (), and subtle functional difficulties relate to amyloid and cognition even among cognitively normal older adults (). Together, these findings support IADL assessment as a pragmatic early window into aging-related neurocognitive vulnerability and dementia risk (). Despite growing interest, several important questions remain unresolved. First, many studies assess IADL and cognition concurrently, limiting inference about whether functional impairment precedes subsequent cognitive deterioration. Second, longitudinal evidence is often derived from single cohorts or clinic-based samples, with limited cross-national replication. Cultural and contextual differences may influence both IADL reporting and its relationship with cognition, and cross-cultural adaptation of self-report measures is itself a non-trivial methodological issue (; ). Third, heterogeneity in IADL definitions and cognitive outcomes has limited comparability across studies. Finally, functional ability may change subtly over time in individuals with early cognitive vulnerability, highlighting the need for designs that explicitly model temporal ordering ().