Olfactory identification decline: a preclinical biomarker for Alzheimer's Disease




Knight, Jamie

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The earliest stage of Alzheimer’s disease (AD) pathology begins in one of the main components of the olfactory pathway, the entorhinal cortex, making deficits in smell a potential prospective biomarker for the early detection of AD. This study contributes to the field with a reproduction and extension of work by Wilson, Arnold, Schneider, Boyle, Buchman, and Bennett (2009). A sample of 1089 individuals (M=78.4 years), more than double the data available in 2009, completed annual assessments of olfactory functioning, and cognitive functioning for up to 18 years with brain donation at death. Mixed effects models conditioned on demographics estimated between and within-person effects in olfactory functioning and episodic memory (EM). After successful reproduction of Wilson et al. (2009), addition of AD pathology (ADP) demonstrated that both ADP and olfaction were significantly related to EM at baseline. Higher ADP at autopsy was significantly related to faster declines in olfaction, as well as more rapid declines in EM. Higher olfactory scores were associated with higher EM scores and a model for EM with olfaction as time-varying covariate indicated that at a given occasion, individuals with higher olfactory scores also have higher EM scores. These results align with the hypotheses that difficulty in identifying odors predicts development of cognitive impairment; increased levels of AD pathology are related to both decreased EM at baseline and faster declines, as well as faster rates of decline in olfaction; and olfaction and cognition are travelling together over time.



dementia, neurodegenerative, olfaction, smell, cognitive decline, Alzheimer’s, olfactory