Odor identification as a biomarker of preclinical AD in older adults at risk

Abstract

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.

Intact global cognitive and olfactory ability predicts lack of transition to dementia

“…Other biomarkers have been studied in relation to olfaction. In a cross‐sectional study, impaired odor identification was associated with increased CSF t‐tau and p‐tau 181 to Aβ 1‐42 ratio, which is the CSF signature of AD brain pathology . In another cross‐sectional study, cognitively normal older adults with elevated brain amyloid on positron emission tomography (PET) and thinner entorhinal cortices on magnetic resonance imaging had lower odor identification test scores .…”

Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes

“…Furthermore, reduced activation in the primary olfactory cortex was observed in patients with Alzheimer disease compared with cognitively normal control subjects and was significantly correlated with poor cognitive performance (10). Therefore, olfactory dysfunction is considered one of the earliest manifestations of neurodegenerative diseases (11) and a potential preclinical marker for future cognitive decline (12). Of note, olfactory-related regions are the brain regions with the highest level of insulin receptors (13), whereas neuronal activity of the olfactory system is modulated by insulin (14).…”

Open Science Datasets from PREVENT-AD, a Longitudinal Cohort of Pre-symptomatic Alzheimer’s Disease

“…In a leave-one-out analysis, we assessed the reliability of the UPSIT in the PREVENT-AD cohort among an initial sample of 159 participants, obtaining a Cronbach α of 0.821, which suggests high internal consistency. 36,37 We tested central auditory processing (CAP) using the Synthetic Sentence Identification with Ipsilateral Competing Message (SSI-ICM) test and the Dichotic Stimulus Identification (DSI) test. After having first been assessed for simple auditory acuity (with monosyllabic words), participants were asked to identify spoken "pseudo-sentences," either with various sound levels of a distracting background narrative (SSI-ICM) or with dichotic binaural presentation (DSI).…”

“…In brief, several analyses demonstrated novel association, correlation or prediction among various direct and derived measures of AD pathology, including MRI, CSF biomarkers of AD, protein mediators of innate immune activity, and neurosensory faculties. 18,36,38,[48][49][50] In addition to the INTREPAD trial derived results publications associations were established between measures of AD pathology (revealed by MRI and/or CSF proteins) and subjective cognitive decline, and proximity to age at onset of parental AD symptoms. 18,[51][52][53][54] Novel MRI techniques and disease progression modelling were also validated in this dataset.…”