A digital remote olfactory assessment developed by researchers at Massachusetts General Hospital may provide a cost-effective, noninvasive screening method for preclinical Alzheimer's disease and other neurocognitive disorders.

The AROMHA Brain Health Test (ABHT), described in a new study published in Scientific Reports, is capable of evaluating olfactory function through odor identification, discrimination, memory, and intensity assessments. The at-home self-administered test successfully differentiated between cognitively normal older adults and those with mild cognitive impairment (MCI), while also detecting age-related olfactory decline.

"Olfactory neural circuits develop Alzheimer's disease (AD) pathologic changes prior to symptom onset," the study authors wrote. "To probe these vulnerable circuits, we developed the digital remote ... ABHT, an at-home odor identification, discrimination, memory, and intensity assessment," they detailed.

The researchers enrolled cognitively normal (CN) English and Spanish speakers (n = 127), participants with subjective cognitive complaints (SCC; n = 34), and MCI (n = 19). Tests were conducted remotely at home under both observed and unobserved conditions, as well as in person with a research assistant present.

The researchers found that olfactory performance was similar across observed and unobserved remote self-administration and between English and Spanish speakers. Notably, odor memory, identification, and discrimination scores decreased with age, and olfactory identification and discrimination were significantly lower in the MCI group compared with the CN and SCC groups, independent of age, sex, and education.

"The ABHT revealed age-related olfactory decline and discriminated CN older adults from those with cognitive impairment," the study authors reported.

The test leveraged the fact that many brain regions process olfactory input, and these regions are damaged early in neurodegenerative disease progression. The olfactory bulb and entorhinal cortex were among the first sites of tau pathology, and the amygdala and piriform cortices were also early sites of tau pathology in AD.

Olfactory performance has been associated with AD biomarkers, including elevated levels of cerebrospinal fluid (CSF) and PET tau. Poorer performance was associated with smaller hippocampal volume in older adults and in patients with cognitive impairment on the AD clinical continuum. This biological basis may provide a strong rationale for utilizing olfactory testing as an early screening approach.

The ABHT consisted of three main components:

• Odor Percept Identification (OPID) test, where participants smelled an odor, answered a question, and chose from four provided odor names

• Percept of Odor Episodic Memory (POEM) test, where participants distinguished between new odors and those presented earlier

• Odor Discrimination (OD) test, where participants identified pairs of smells as either the same or different.

The test also incorporated a metacognition measure embedded in the odor identification tasks, asking participants to rate their confidence in each identification decision with options ranging from "I guessed" to "I am certain." This metacognitive assessment added a critical dimension, as metacognition metrics are predictive of cognitive decline and biomarkers in patients with AD or MCI.

The researchers validated the ABHT in multiple ways:

• Comparing observed vs unobserved remote self-administration (finding equivalent performance)

• Testing in both English and Spanish speakers (finding no statistically significant differences)

• Validating in anosmic patients (n = 7) who performed at chance level as expected

• Comparing performance across age ranges and cognitive status groups.

When assessed across age groups, greater age was significantly associated with lower scores on OPID9noguess, OPID18, OPID18noguess, OD10, and POEM tests, confirming the test's sensitivity to age-related olfactory decline.

Senior study author Mark W. Albers, MD, PhD, a neurologist at Massachusetts General Hospital, suggested that this test could facilitate the early detection of neurodegenerative diseases. "A cost-effective, noninvasive screen for preclinical AD performed at home would enable important research in this area by affording a means for more efficient screening, such as blood-based biomarkers and imaging, for eligibility criteria for clinical trials targeting preclinical or early-stage disease," Dr. Albers and his colleagues indicated.

The study design allowed for validation of the test across different administration modalities and demonstrated that the test was sensitive to both aging and cognitive decline, suggesting its potential utility in clinical research settings.

"These results suggest that the ABHT could be used in clinical research settings in different languages to explore the utility of olfactory biomarkers to predict the presence of blood-based, image-based, or CSF-based biomarkers of neurodegenerative disease and longitudinal development of clinical symptoms," the study authors concluded.

Full disclosures can be found in the study.