Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly

Abstract

Objective To relate a novel test of identifying and recalling odor percepts to biomarkers of Alzheimer’s Disease (AD) in well-characterized elderly individuals, ranging from cognitively normal to demented. Methods 183 participants (cognitively normal: n=70, subjective cognitive concerns: n=74, Mild Cognitive Impairment (MCI): n=29, AD dementia: n=10) were administered novel olfactory tests: the Odor Percept IDentification (OPID) and the Percepts of Odor Episodic Memory (POEM) tests. Univariate cross-sectional analyses of performance across diagnoses; logistic regression modeling including covariates of age, gender, education, APOE genotype, and neuropsychological test scores; and linear mixed modeling of longitudinal cognitive scores were performed. Amyloid deposition and MRI volumetrics were analyzed in a subset of participants. Results Accuracy of identification and episodic memory of odor percepts differed significantly across diagnosis and age, with progressively worse performance across degrees of impairment. Among the participants who were cognitively normal or had subjective cognitive concerns, poorer than expected performance on the POEM test (based on the same individual’s performance on the OPID and odor discrimination tests) was associated with higher frequencies of the APOE ε4 allele, thinner entorhinal cortices, and worse longitudinal trajectory of Logical Memory scores. Interpretation Selective impairment of episodic memory of odor percepts, relative to identification and discrimination of odor percepts revealed by this novel POEM battery, is associated with biomarkers of AD in a well-characterized pre-MCI population. These affordable, non-invasive olfactory tests offer potential to identify clinically normal individuals who have greater likelihood of future cognitive decline.

The Brief Form of the California Odor Learning Test 3

“…As expected based on these observations, deficits in odor identification have been observed to be associated with mild cognitive impairment (Eibenstein et al, 2005b), conversion from mild cognitive impairment to AD (Devanand et al, 2000;Roberts et al, 2016), and with patients diagnosed with probable or questionable AD (Kesslak et al, 1988;Serby et al, 1991;Morgan et al, 1995). In addition, deficits in odor recall, recognition, and familiarity have been found to be associated with mild cognitive impairment and AD (Nordin and Murphy, 1998;Niccoli-Waller et al, 1999;Dhilla Albers et al, 2016). Deficits in odor identification and memory have also been observed to be associated with the genetic risk factor for AD, the apolipoprotein e4 (APOE) allele (Murphy et al, 1998;Gilbert and Murphy, 2004a,b;Calhoun-Haney and Murphy, 2005;Handley et al, 2006;Olofsson et al, 2010Olofsson et al, , 2020.…”

“…In addition, medial temporal lobe areas important in memory and cognition have been associated with odor recall and recognition deficits in lesion studies (Rausch et al, 1977;Eibenstein et al, 2005a). Decreases in odor identification and odor memory have also been associated with decreases in volume of the hippocampus, decreases in entorhinal cortex thickness, and worse episodic memory (Murphy et al, 2003;Growdon et al, 2015;Dhilla Albers et al, 2016). As expected based on these observations, deficits in odor identification have been observed to be associated with mild cognitive impairment (Eibenstein et al, 2005b), conversion from mild cognitive impairment to AD (Devanand et al, 2000;Roberts et al, 2016), and with patients diagnosed with probable or questionable AD (Kesslak et al, 1988;Serby et al, 1991;Morgan et al, 1995).…”

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

“…We note that our findings appear to contradict one recent report in which OI appeared not to be related to brain accumulation of amyloid as revealed by PET. 32 As we did, the authors of that study attempted to control for known detrimental olfactory health issues. They chose to exclude participants with such issues.…”

Cognitive Impairment and Structural Abnormalities in Late Life Depression with Olfactory Identification Impairment: an Alzheimer’s Disease-Like Pattern

“…Therefore, OI impairment is considered to reflect the extent of cognitive impairment and brain malfunction in older individuals. In cross-sectional studies, individuals with diminished OI exhibited worse cognitive performance (memory, execution function, and language) ( Roberts et al, 2016 ), reduced hippocampal volume (HV) and olfactory bulb volume (OBV) ( Thomann et al, 2009 ), a thinner entorhinal cortex, increased cortical amyloid burden ( Growdon et al, 2015 ), reduced blood flow in the frontotemporal lobe ( Wang et al, 2010 ), lower ratios of CSF t-tau and P 181 -tau to Aβ 1–42 ( Lafaillemagnan et al, 2017 ), and a high proportion of these patients were APOE ε4 carriers ( Dhilla et al, 2016 ). In a longitudinal study, OI impairment predicted a faster cognitive decline and higher rate of conversion to AD in amnestic mild cognitive impairment (aMCI) patients and elderly controls ( Roberts et al, 2016 ), particularly in combination with neuropsychological assessments and neuroimaging evaluations ( Devanand et al, 2008 ; Lojkowska et al, 2011 ).…”