Olfactory Identification Deficits, Cognitive Decline, and Dementia in Older Adults

Abstract

Several recently developed biomarkers of Alzheimer disease (AD) are invasive, expensive, and difficult to obtain in most clinical settings. Olfactory identification test performance represents a noninvasive, inexpensive biomarker of AD that may have predictive accuracy comparable with neuroimaging measures and biomarkers assessed in cerebrospinal fluid. Neurofibrillary tangles in the olfactory bulb are among the earliest pathologic features of AD and are also seen in the projection pathways from the olfactory bulb to secondary olfactory brain regions, including the piriform and medial temporal cortex, orbitofrontal cortex, and other limbic regions. Odor identification impairment characterizes AD and predicts the clinical transition from mild cognitive impairment to AD in both clinical and community samples. Epidemiologic data indicate that in cognitively intact older adults, impairment in odor identification predicts cognitive decline but that episodic verbal memory impairment does not predict cognitive decline. Odor identification impairment has also been shown to predict mortality in older subjects with mortality risk increasing with greater severity of impairment in odor identification. The exact cause of this association is not known, but olfactory deficits may lead to an increase in accidents in the home, because of the inability to smell and taste food that is unsafe or not smelling a gas leak or fire, and this may increase mortality risk. Standardized tests of odor identification ability are widely available and may provide a useful tool to improve diagnostic and predictive accuracy for cognitive decline, AD, and mortality in older adults.

Th17 lymphocytes drive vascular and neuronal deficits in a mouse model of postinfectious autoimmune encephalitis

“…Recent studies have established anosmia as a prodromal biomarker for Alzheimer's disease (48)(49)(50) and the presence of olfactory deficits in a subset of MS patients correlating with symptom severity (51,52). GAS-infected mice show severe persistent physiological deficits in M/ T neuronal function (Fig.…”

Mechanisms Linking Olfactory Impairment and Risk of Mortality

“…Two found that the association between OI and mortality was lowered when controlling for dementia, yet remained statistically significant. Of note, OI was shown to be associated with future cognitive decline in cognitively intact subjects (Devanand, 2016). Moreover, there is evidence of existing post-mortem markers of neurodegenerative disease in the brain of subjects without previous clinical signs of MCI or AD (Wilson et al, 2009).…”

“…It is known that approximately 70% of MCI patients will ultimately convert to AD (Gauthier et al, 2006). Yet, recent data converge toward the idea that olfactory-impaired MCI patients are more prone to develop AD than those without OI (Conti et al, 2013;Devanand, 2016;Adams et al, 2018;Jung et al, 2019). Overall, these findings make OI a potential early predictor for AD development.…”

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

“…The oral‐nasal‐olfactory system is regarded as a direct portal for bacterial pathogens to the brain, and olfactory system dysfunction leads to neurodegeneration. Olfactory dysfunction is present in up to 90% of patients with AD; the olfactory bulb neurofibrillary tangles are among the earliest pathologic features of AD and human and animal behavioral studies provide indication that olfactory dysfunction can occur early in the AD process, even at a preclinical stage …”