The AD Spectrum Hypothesis and A Multidomain Behavioral Framework for Early Detection

Early diagnosis of Alzheimer’s disease (AD) remains limited by reliance on cognitive symptoms that appear only after significant neurodegeneration has occurred. Although the traditional memory-first model assumes that early pathology begins in medial temporal lobe structures, growing evidence shows that initial decline often emerges in distributed association cortices that support sensory processing, perceptual integration, motor planning, timing precision, executive control, and affective regulation. These findings motivate the AD Spectrum Hypothesis, which proposes that early AD manifests through heterogeneous combinations of sensory, perceptual, motor, cognitive, and emotional changes rather than a uniform trajectory of episodic memory loss. To evaluate whether existing behavioral tasks capture this multidomain variability, we reviewed studies comparing healthy controls, individuals with mild cognitive impairment (MCI), and individuals with early AD using the Sensation, Perception, Action, Cognition, Emotion (SPACE) framework. Across modalities, MCI and early AD showed graded impairments in anticipatory motor control, gait dynamics, speech acoustics, visuomotor organization, fine-motor timing, perceptual stability, and emotional modulation. These findings indicate that early AD affects multiple functional systems and is most sensitively detected by tasks that engage several SPACE domains simultaneously. Based on this evidence, we propose a multidomain behavioral battery as a promising noninvasive approach for improving early detection of AD.