Complexity of Frontal Cortex fNIRS Can Support Alzheimer Disease Diagnosis in Memory and Visuo-Spatial Tests

Decline in visuo-spatial skills and memory failures are considered symptoms of Alzheimer's Disease (AD) and they can be assessed at early stages employing clinical tests. However, performance in a single test is generally not indicative of AD. Functional neuroimaging, such as functional Near Infrared Spectroscopy (fNIRS), may be employed during these tests in an ecological setting to support diagnosis. Indeed, neuroimaging should not alter clinical practice allowing free doctor-patient interaction. However, block-designed paradigms, necessary for standard functional neuroimaging analysis, require tests adaptation. Novel signal analysis procedures (e.g., signal complexity evaluation) may be useful to establish brain signals differences without altering experimental conditions. In this study, we estimated fNIRS complexity (through Sample Entropy metric) in frontal cortex of early AD and controls during three tests that assess visuo-spatial and short-term-memory abilities (Clock Drawing Test, Digit Span Test, Corsi Block Tapping Test). A channel-based analysis of fNIRS complexity during the tests revealed AD-induced changes. Importantly, a multivariate analysis of fNIRS complexity provided good specificity and sensitivity to AD. This outcome was compared to cognitive tests performances that were predictive of AD in only one test. Our results demonstrated the capabilities of fNIRS and complexity metric to support early AD diagnosis.