Novel diagnostic tools for identifying cognitive impairment using olfactory-stimulated functional near-infrared...

Basic studies suggest that olfactory dysfunction and functional near-infrared spectroscopy (fNIRS) can be used as tools for the diagnosis of mild cognitive impairment (MCI); however, real-world evidence is lacking. We investigated the potential diagnostic efficacy of olfactory-stimulated fNIRS for early detection of MCI and/or Alzheimer disease (AD).

We conducted a patient-level, single-group, diagnostic interventional trial involving elderly volunteers (age >60 years) suspected of declining cognitive function. Patients received open-label olfactory-stimulated fNIRS for measurement of oxygenation difference in the orbitofrontal cortex. All participants underwent amyloid PET, MRI, Mini-Mental State Examination (MMSE), and Seoul Neuropsychological Screening Battery (SNSB).

Of 97 subjects, 28 (28.9%) were cognitively normal, 32 (33.0%) had preclinical AD, 21 (21.6%) had MCI, and 16 (16.5%) had AD. Olfactory-stimulated oxygenation differences in the orbitofrontal cortex were associated with cognitive impairment; the association was more pronounced with cognitive severity. Olfactory-stimulated oxygenation difference was associated with MMSE (adjusted β [aβ] 1.001; 95% CI 0.540-1.463), SNSB language and related function (aβ, 1.218; 95% CI, 0.020-2.417), SNSB memory (aβ, 1.963; 95% CI, 0.841-3.084), SNSB frontal/executive function (aβ, 1.715; 95% CI, 0.401-3.029) scores, standard uptake value ratio from amyloid PET (aβ, -10.083; 95% CI, -19.063 to -1.103), and hippocampal volume from MRI (aβ, 0.002; 95% CI, 0.001-0.004). Olfactory-stimulated oxygenation difference in the orbitofrontal cortex was superior in diagnosing MCI and AD (AUC, 0.909; 95% CI, 0.848-0.971), compared to amyloid PET (AUC, 0.793; 95% CI, 0.694-0.893) or MRI (AUC, 0.758; 95% CI, 0.644-0.871).

Our trial showed that olfactory-stimulated oxygenation differences in the orbitofrontal cortex detected by fNIRS were associated with cognitive impairment and cognitive-related objectives. This novel approach may be a potential diagnostic tool for patients with MCI and/or AD.

CRIS number, KCT0006197 .