The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Odor identification as a biomarker of preclinical AD in older adults at risk
Open accessAbstract
Objective: To assess odor identification (OI) as an indicator of presymptomatic Alzheimer disease (AD) pathogenesis in cognitively normal aging individuals at increased risk of AD dementia. Methods: In 274 members of the PREVENT-AD cohort of healthy aging persons with a parental or multiple-sibling history of AD dementia, we assessed the cross-sectional association of OI with potential indicators of presymptomatic AD. Some 101 participants donated CSF, thus enabling assessment of AD pathology with the biomarkers total tau (t-tau), phospho-tau (P181-tau), and their ratios with β-amyloid (Aβ1-42). Adjusted analyses considered age, cognition, APOE ε4 status, education, and sex as covariates. We measured OI using the University of Pennsylvania Smell Identification Test and cognitive performance using the Repeatable Battery for Assessment of Neuropsychological Status. Standard kits provided assays of the AD biomarkers. Analyses used robust-fit linear regression models. Results: Reduced OI was associated with lower cognitive score and older age, as well as increased ratios of CSF t-tau and P181-tau to Aβ1-42 (all p < 0.02). However, the observed associations of OI with age and cognition were unapparent in adjusted models that restricted observations to CSF donors and included AD biomarkers. OI showed little association with CSF Aβ1-42 alone except in APOE ε4 carriers having lowest-quartile Aβ1-42 levels. Conclusions: These findings from healthy high-risk older individuals suggest that OI reflects degree of preclinical AD pathology, while its relationships with age and cognition result from the association of these latter variables with such pathology. Diminished OI may be a practical and affordable biomarker of AD pathology.
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“the connection to the entorhinal cortex, the olfactory bulb, is directly affected by changes in the perforant pathway, and one of the earliest pathological changes in AD”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [43]
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“the amyloid deposition spreads, and the disease pathogenesis progressively involves a broad region of the brain”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [43]
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Cites
The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment
Nasreddine, Z. S., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J. L., & Chertkow, H. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53221.x · Cited by 25,553
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A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056
Randolph, C., Tierney, M. C., Mohr, E., & Chase, T. N. (1998) · Journal of Clinical and Experimental Neuropsychology · doi:10.1076/jcen.20.3.310.823 · Cited by 2,519 · cited 1×
“Assessments included a health history and review of systems, a standardized neurologic examination, and a cognitive examination with version A of the Repeatable Battery for Assessment of Neuropsychological Status (RBANS).(21)”
MethodDoty, R. L., Shaman, P., & Dann, M. (1984) · Physiology & Behavior · doi:10.1016/0031-9384(84)90269-5 · Cited by 1,854 · cited 1×
“We assessed OI abilities using the 40-item University of Pennsylvania Smell Identification Test (UPSIT).(23) This test includes a simple scratch-and-sniff booklet along with multiple-choice response forms for OI.”
MethodThe influences of age on olfaction: a review
Doty, R. L., & Kamath, V. J. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.00020 · Cited by 681
Roberts, R. O., Christianson, T. J. H., Kremers, W. K., Mielke, M. M., Machulda, M. M., Vassilaki, M. E., Alhurani, R. E., Geda, Y. E., Knopman, D. S., & Petersen, R. C. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.2952 · Cited by 437
Devanand, D. P., Liu, X., Tabert, M. H., Pradhaban, G., Cuasay, K., Bell, K. L., de Leon, M. J., Doty, R. L., Stern, Y., & Pelton, G. H. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.020 · Cited by 413
Olfaction in patients with mild cognitive impairment and Alzheimer's disease
Djordjevic, J., Jones‐Gotman, M., Sousa, K. D., & Chertkow, H. M. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.11.014 · Cited by 365
Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community
Devanand, D. P., Lee, S., Manly, J. J., Andrews, H., Schupf, N., Doty, R. L., Stern, Y., Zahodne, L. B., Louis, E. D., & Mayeux, R. P. (2014) · Neurology · doi:10.1212/wnl.0000000000001132 · Cited by 351
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Olfactory and other sensory impairments in Alzheimer disease
Murphy, C. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0097-5 · Cited by 425
Olfactory Dysfunction in Neurodegenerative Diseases
Marín, C., Vilas, D., Langdon, C., Alobid, I., López‐Chacon, M., Haehner, A., Hummel, T. R., & Mullol, J. (2018) · Current Allergy and Asthma Reports · doi:10.1007/s11882-018-0796-4 · Cited by 303
Neural oscillations and brain stimulation in Alzheimer’s disease
Jafari, Z., Kolb, B. E., & Mohajerani, M. H. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101878 · Cited by 192
AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 176
“Of interest, the connection to the entorhinal cortex, the olfactory bulb, is directly affected by changes in the perforant pathway, and one of the earliest pathological changes in AD.(43,49) Similarly, the loss of visual recognition is a characteristic pathology associated with AD.”
BackgroundInfluentialInternational consensus statement on allergy and rhinology: Olfaction
Patel, Z. M., Holbrook, E. H., Turner, J. H., Adappa, N. D., Albers, M. W., Altundağ, A., Appenzeller, S., Costanzo, R. M., Croy, I., Davis, G. E., et al. (2022) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22929 · Cited by 142
Metadata
- Authors
- Lafaille-Magnan, M.-E., Poirier, J., Etienne, P., Tremblay-Mercier, J., Frenette, J., Rosa-Neto, P., Breitner, J. C. S., & For the PREVENT-AD Research Group
- Affiliations
- From the Centre for Studies on Prevention of AD (M.-E.L.-M., J.P., P.E., J.T.-M., J.F., P.R.-N., J.C.S.B.) and McGill Centre for Studies in Aging (P.R.-N.), Douglas Mental Health University Institute, McGill University, Faculty of Medicine, Montreal, Quebec, Canada.
- Douglas Mental Health University Institute (CA)
- Venue
- Neurology
- Published
- 2017-07-25
- Volume
- 89
- Issue
- 4
- Pages
- 327-335
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC5574678
- OpenAlex
- W2732607734
- Cited by
- 145
- References
- 38
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 18 · 2023: 16 · 2022: 12 · 2021: 21 · 2020: 20 · 2019: 13 · 2018: 21 · 2017: 3
- FWCI
- 12.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Neurology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- McGill University
- Weston Brain Institute
- Consortium canadien en neurodégénérescence associée au vieillissement
- TauRx Pharmaceuticals
- Government of Canada
- Pfizer Canada
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- odor identification, smell impairment, preclinical Alzheimer's disease, Alzheimer's disease biomarkers, cerebrospinal fluid tau, phosphorylated tau, amyloid-beta 42, APOE ε4, cognitively normal older adults, high-risk families, olfaction, cognitive aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Cognition, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Peptide Fragments, Phosphorylation, Risk, Cohort Studies, Biomarkers, Amyloid beta-Peptides, tau Proteins, Recognition, Psychology, Pattern Recognition, Physiological, Apolipoprotein E4, Olfactory Perception, Prodromal Symptoms
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