Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging

Woodward, Matthew R.; Hafeez, Muhammad Ubaid; Qi, Qianya; Ahmed, Rayaz; Benedict, Ralph; Li, Yan; Szigeti, Kinga; Pavlik, Valory N.; Massman, Paul J.; Darby, Eveleen; Rodriguear, Monica; Ansari, Aisha Khaleeq; DeToledo, John C.; Reddy, Hemachandra; Wilms, Henrick; Johnson, Kurt E.; Perez, Victoria; Fairchild, Thomas J.; Knebl, Janice; O’Bryant, Sid; Hall, James; Johnson, Leigh; Barber, Robert C.; Mains, Douglas A.; Alvarez, Luis; Cullum, Munro; Rosenberg, Roger N.; Williams, Benjamin; Quiceno, Mary; Reisch, Joan; Hynan, Linda S.; Huebinger, Ryan M.; Smith, Janet; Nguyen, Trung; Royall, Donald R.; Palmer, Raymond F.; Polk, Marsha J.; Stevens, Alan; Ory, Marcia G.; Paydarfar, David; Bertelson, John; Woon, Martin; Ayres, Gayle; Aguirre, Alyssa; Wilhelmsen, Kirk C.; Tilson, Jeffrey L.

doi:10.1016/j.jagp.2018.02.008

Cited by 28 publications

(20 citation statements)

References 41 publications

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“…This is consistent with prior studies in Alzheimer's disease and Parksinson's disease showing that decrements in identification of particular scents are specific for these pathologies. 24,25 For example, in our sinonasal cohort, orange was only identified correctly by 26% of subjects. Rose and anise were also problematic for the sinonasal cohort.…”

Section: Discussionmentioning

confidence: 71%

Affordable Rapid Olfaction Measurement Array: A Novel, Essential Oil-Based Test Strongly Correlated with UPSIT and Subjective Outcome Measures

Villwock

Moore

et al. 2019

Ann Otol Rhinol Laryngol

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Background: Olfactory dysfunction is an important facet of numerous disease states ranging from sinonasal disease to neurocognitive disorders. Due to expense and/or logistical barriers, objective olfactory testing is not common. We describe the creation of a novel, essential oil-based smell test, Affordable Rapid Olfaction Measurement Array (AROMA), composed at 14 scents at different concentrations and demonstrate correlation of AROMA with the University of Pennsylvania Smell Identification Test (UPSIT), patient age, Sinonasal Outcomes Test (SNOT-22), and perceived loss of smell. Methods: AROMA was developed for point-of-care olfactory testing and compared to the UPSIT, as well as subjective outcome measures as noted above. About 37 healthy controls were prospectively recruited to assess the reliability of AROMA using a test–retest protocol. An additional cohort of 38 participants with sinonasal disease were prospectively recruited to complete the AROMA and UPSIT, and were compared with a cohort of 30 healthy controls. Spearman correlation correlated AROMA and UPSIT results, patient age, SNOT-22, and perceived loss of smell. Results: AROMA demonstrated good test–retest reliability ( r = 0.85, P < .001). Spearman’s rho correlation of AROMA to UPSIT was statistically significant at ρ = 0.75 ( P < .001). SNOT-22, age, and perceived sense of smell were all significantly correlated with both AROMA (ρ = −0.548, −0.557, −0.642, respectively) and UPSIT (ρ = −0.367, −0.460, −0.552, respectively). Conclusion: AROMA has a strong correlation with UPSIT and may be more strongly correlated with sinonasal outcomes. Additionally, AROMA is reusable; level of odorant is not static; and AROMA can test both odor detection and identification. Level of evidence: 2b

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Section: Discussionmentioning

confidence: 71%

Affordable Rapid Olfaction Measurement Array: A Novel, Essential Oil-Based Test Strongly Correlated with UPSIT and Subjective Outcome Measures

Villwock

Moore

et al. 2019

Ann Otol Rhinol Laryngol

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“…The University at Buffalo Alzheimer's Disease and Memory Disorders Center clinical research cohort is an observational study with genetic component [ 23 , 24 ]. Inclusion criteria included consensus diagnosis of aMCI or AD, documentation of time of initiation of AChEI therapy, baseline MMSE within 3 months prior to AChEI initiation, at least 1 follow up assessment within 3–7 months after AChEI initiation, age >55, male or female, any race.…”

Section: Methodsmentioning

confidence: 99%

CHRFAM7A: A human specific fusion gene, accounts for the translational gap for cholinergic strategies in Alzheimer's disease

et al. 2020

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Background Cholinergic neuronal loss is one of the hallmarks of AD related neurodegeneration; however, preclinical promise of α7 nAChR drugs failed to translate into humans. CHRFAM7A , a uniquely human fusion gene, is a negative regulator of α7 nAChR and was unaccounted for in preclinical models. Methods Molecular methods: Function of CHRFAM7A alleles was studied in vitro in two disease relevant phenotypic readouts: electrophysiology and Aβ uptake. Genome edited human induced pluripotent stem cells (iPSC) were used as a model system with the human context. Double blind pharmacogenetic study: We performed double-blind pharmacogenetic analysis on the effect of AChEI therapy based on CHRFAM7A carrier status in two paradigms: response to drug initiation and DMT effect. Mini Mental Status Examination (MMSE) was used as outcome measure. Change in MMSE score from baseline was compared by 2-tailed T-test. Longitudinal analysis of clinical outcome (MMSE) was performed using a fitted general linear model, based on an assumed autoregressive covariance structure. Model independent variables included age, sex, and medication regimen at the time of the first utilized outcome measure (AChEI alone or AChEI plus memantine), APOE4 carrier status (0, 1 or 2 alleles as categorical variables) and CHRFAM7A genotype. Findings The direct and inverted alleles have distinct phenotypes. Functional CHRFAM7A allele classifies the population as 25% non-carriers and 75% carriers. Induced pluripotent stem cell (iPSC) models α7 nAChR mediated Aβ neurotoxicity. Pharmacological readout translates into both first exposure ( p = 0.037) and disease modifying effect ( p = 0.0048) in two double blind pharmacogenetic studies. Interpretation CHRFAM7A accounts for the translational gap in cholinergic strategies in AD. Clinical trials not accounting for this uniquely human genetic factor may have rejected drug candidates that would benefit 25% of AD. Reanalyses of the completed trials using this pharmacogenetic paradigm may identify effective therapy. Funding:

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“…Therefore, olfactory dysfunction is expected to be one of the biomarkers to predict progression from normal cognitive status or MCI to AD (Adams et al, 2018;Windon et al, 2020). One study reported that a specific pattern of olfactory identification deficit may differentiate AD from age-related olfactory loss (Woodward et al, 2018). PD represents the second-largest neurodegenerative population after AD.…”

Section: Olfactory Dysfunction Associated With Neurodegenerative Disementioning

confidence: 99%

Age-Related Olfactory Dysfunction: Epidemiology, Pathophysiology, and Clinical Management

Kondo

Kikuta

Ueha

et al. 2020

Front. Aging Neurosci.

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Like other sensory systems, olfactory function deteriorates with age. Epidemiological studies have revealed that the incidence of olfactory dysfunction increases at the age of 60 and older and males are more affected than females. Moreover, smoking, heavy alcohol use, sinonasal diseases, and Down's syndrome are associated with an increased incidence of olfactory dysfunction. Although the pathophysiology of olfactory dysfunction in humans remains largely unknown, studies in laboratory animals have demonstrated that both the peripheral and central olfactory nervous systems are affected by aging. Aged olfactory neuroepithelium in the nasal cavity shows the loss of mature olfactory neurons, replacement of olfactory neuroepithelium by respiratory epithelium, and a decrease in basal cell proliferation both in the normal state and after injury. In the central olfactory pathway, a decrease in the turnover of interneurons in the olfactory bulb (OB) and reduced activity in the olfactory cortex under olfactory stimulation is observed. Recently, the association between olfactory impairment and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), has gained attention. Evidence-based pharmacotherapy to suppress or improve age-related olfactory dysfunction has not yet been established, but preliminary results suggest that olfactory training using odorants may be useful to improve some aspects of age-related olfactory impairment.

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Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging

Cited by 28 publications

References 41 publications

Affordable Rapid Olfaction Measurement Array: A Novel, Essential Oil-Based Test Strongly Correlated with UPSIT and Subjective Outcome Measures

Affordable Rapid Olfaction Measurement Array: A Novel, Essential Oil-Based Test Strongly Correlated with UPSIT and Subjective Outcome Measures

CHRFAM7A: A human specific fusion gene, accounts for the translational gap for cholinergic strategies in Alzheimer's disease

Age-Related Olfactory Dysfunction: Epidemiology, Pathophysiology, and Clinical Management

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