Olfactory function and neurocognitive outcomes in old age: The Atherosclerosis Risk in Communities Neurocognitive Study

Abstract

An impaired sense of smell may serve as a readily accessible early marker of neurodegeneration and improve upon the prevailing delayed diagnoses and underascertainment of MCI/dementia.

Could Early Identification of Changes in Olfactory Function Be an Indicator of Preclinical Neurodegenerative Disease? A Systematic Review

“…1 PRISMA flowchart of selected studies included in this systematic review [45] Covariates Age, sex and education were included as a covariate in each of the studies. As shown by Table 6, apolipoprotein E (APOE) e4 was considered in three of the nine studies [48][49][50]. Kreisl et al found no correlation between UPSIT scores and APOE e4 status (OR 1.75; 95% CI 0.56, 5.44; p = 0.3352), and also that APOE e4 status was not significantly higher in MCI in comparison to HC (p = 0.4488) [49].…”

“…Woodward et al found that APOE e4 status was higher in both MCI and AD when compared to HC; however, odour identification deficiency was independent from APOE e4 status [48]. Furthermore, smoking is included as a covariate in four articles [46,48,50,51] Medication Use of Participants Table 7 shows that only three of the nine included articles considered medication use in their study design or as a covariate [49,50,52], and one stated lack of consideration as a limitation [48]. Even when medication use was included in the study design, there was typically only consideration of a specific type, such as psychotropics, and did not account for all medications a participant may be taking.…”

“…Brief conclusion summary of individual articles included in this systematic review. All articles found a correlation between OI and MCI and/or AD, suggesting its value as a supplementary tool alongside other diagnostic testing EOAD early onset Alzheimer's disease, eoMCI early onset mild cognitive impairment, aMCI amnestic mild cognitive impairment, HC healthy control, OI olfactory impairment, MCI mild cognitive impairment participants from four separate US states [50], therefore largely negating selection bias.…”

“…Smoking is also known to cause a decrease in olfaction; however, a systematic review by Ajmani et al concluded that ex-smokers were found to have the same function as those that never smoked, suggesting a reversibility on cessation [58]. Again, current or previous smokers were only included in the exclusion criteria in the minority of articles [49,51,53] and considered as covariates in four others [46,48,50,51]. As the evidence demonstrates the many factors that influence olfactory function, it seems that having a minimum standard of inclusion/ exclusion criteria across all future studies would facilitate increasingly accurate conclusions of the associations between OI caused by AD pathology alone.…”

Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer’s Disease

“…Sensory processes such as smelling, hearing, and vision are naturally declining to some extent in aged humans but have been shown to be prodromal of dementia [9,10]. Worsening of olfaction impairments are subsequently predictive of MCI developments and may predict the progression to AD [80][81][82][83]. Several clinical studies have demonstrated early tau pathology in the anterior OB circuit, confirming that dysfunctional olfaction may precede cognitive loss [67,69,84], which indicates a concrete potential for the use of olfaction circuitry function in diagnosis and translational research.…”