Association of <i>APOE ε4</i> Status With Long-term Declines in Odor Sensitivity, Odor Identification, and Cognition in Older US Adults.

Abstract

The <i>APOE</i> ε4 allele confers susceptibility to faster decline in odor identification and subsequently to Alzheimer disease (AD). Odor identification requires recognizing and naming odors and detecting them (odor sensitivity). Whether <i>APOE</i> ε4 is associated with decline of odor sensitivity and whether such decline serves as a harbinger of cognitive decline and AD remains unclear. We determined whether and when <i>APOE</i> ε4 affects decline in odor sensitivity, odor identification, and cognition in the National Social Life Health and Aging Project (NSHAP). We used data from NSHAP, a nationally representative survey study of home-dwelling US older adults. Olfaction was measured over time (odor identification in 2005, 2010, and 2015; odor sensitivity in 2010 and 2015; both using validated tests). Cognition was measured with a modified version of the Montreal Cognitive Assessment in 2010 and 2015. Genotyping was performed using DNA samples collected in 2010. Odor sensitivity and identification were compared among <i>APOE</i> ε4 carriers and noncarriers stratified by age. Relationships between <i>APOE</i> ε4, odor sensitivity, odor identification, and cognition were analyzed in cross-section using ordinal logistic regression and longitudinally using mixed-effects models adjusted for confounders. Odor sensitivity was measured in 865 respondents, odor identification in 1,156 respondents, and cognition in 864 respondents; all these respondents had genetic data available. Odor sensitivity deficits in <i>APOE</i> ε4 carriers were apparent at ages 65-69 years, whereas odor identification deficits did not appear until ages 75-79 years. Subsequently, odor sensitivity did not decline more rapidly with aging in <i>APOE</i> ε4 carriers compared with that in noncarriers (carrier status and aging interaction: odds ratio [OR] 1.44, 95% CI 0.94-2.19, <i>p</i> = 0.092), whereas odor identification declined more rapidly in carriers (aging 10 years interaction: OR 0.26, 95% CI 0.13-0.52, <i>p</i> < 0.001). As expected, and in parallel to odor identification, cognition declined more rapidly in <i>APOE</i> ε4 carriers (interaction: OR 0.55, 95% CI 0.34-0.89, <i>p</i> = 0.015). <i>APOE</i> ε4 affects decline of odor sensitivity earlier than odor identification or cognition. Thus, testing odor sensitivity may be useful to predict future impaired cognitive function. Identifying the mechanism underlying these relationships will elucidate the key role of olfaction in neurodegeneration during aging.