AbstractBackgroundWe aimed to develop a tool for objective measurement of apathy and its differentiation from depression in the context of cognitive impairment.MethodWe exposed older adults with and without cognitive impairment (CI and CN, respectively) to emotional (i.e., positive), aversive and neutral, and to cognitive (congruent; incongruent) stimuli in a virtual reality environment and measured their physiological reactivity as reflected by autonomic nervous system (ANS) functions [heart rate (HR), heart rate variability (HRV), respiration and galvanic skin response (GSR)], and gaze [time to gaze fixation (TTGF) and total fixation duration (TFD)]. Apathy and depression were measured via the Lille Apathy Rating Scale (LARS)‐ and the Geriatric Depression Scale (GDS), respectively.ResultParticipants' characteristics are presented in Tables 1‐2. Compared to CN, CI participants had lower TFD (ANOAVE: F = 7.471, P = 0.006) and GSR reactivity (F = 6.334, P = 0.014) in response to all stimuli. Among participants with CI, those with apathy (LARS score ≥‐7) (n = 21) had shorter TFD compared to those without apathy (F = 19.259, P = 0.001), and those with depression (GDS score ≥5) (n = 46) had longer TFD compared to those without depression ((F = 33.118, P = 0.001) to all stimuli. For all participants, presence of apathy was associated with lower TFD (F = 13.807, P = 0.001) higher TTGF (F = 10.819, P = 0.001), lower HRV reactivity (F = 4.089, P = 0.043) and respiration depth reactivity (F = 8.026, P = 0.005) in response to all stimuli. In contrast, depression was associated with higher TFD (F = 8.448, P = 0.004), lower TTGF (F = 5.290, P = 0.022) and higher HRV reactivity (F = 5.171, P = 0.023) to all stimuli. Increasing LARS scores were negatively associated with respiration rate (R = ‐0.223, P = 0.025) and TFD (R = ‐0.253, P = 0.021) in response to positive emotional stimuli, and with TFD in response to congruent (R = ‐0.265, P = 0.016) and incongruent (R = ‐0.247, P = 0.024) cognitive stimuli. GDS scores were positively associated with HR (R = 0.219, P = 0.049; R = 0.217, P = 0.05 respectively) and respiration depth (R = 0.216, P = 0.048; R = 0.252, P = 0.021 respectively) reactivity to positive and aversive emotional stimuli.ConclusionANS and gaze reactivity to emotional and cognitive stimuli presented in a VR environment is sensitive to cognitive status and to apathy, even in subtle forms. Moreover, this tool can potentially differentiate apathy from depression in the context of cognitive impairment.