Olfactory deficit: a potential functional marker across the Alzheimer’s disease continuum

Abstract

Alzheimer’s disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future.

Air quality and aging brain: Air pollution as a risk factor of developing dementia

“…In addition to mechanical inhalation into the lungs, ambient pollution can trigger damage and inflammation through direct translocation via the olfactory nerve (Hahad et al, 2021;Costa et al, 2017;Costa et al, 2020). It is noteworthy that olfactory deficit is one of the early signs of Alzheimer's disease (Liu et al, 2024;Fatuzzo et al, 2023). Some articles suggest it could be the leadning portal of entry for pollutants (Doty, 2008).…”

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“…Persistent olfactory impairment (POI) and taste disorder (TD) has been proposed as a marker to identify people with an increased long-term risk of several neurological diseases, such as Alzheimer and Parkinson disease (1)(2)(3)(4)(5)(6)(7). Long-term neuropsychological impairments such as executive, attentional, and memory deficits are consistent with sequalae after mild infection with several classes of viral particles.…”