Olfactory impairment in presymptomatic Alzheimer's disease.

Alzheimer's disease (AD) impairs olfaction, but it is uncertain how early this occurs in the disease process and whether the effect can be accounted for by other behavioral or genetic markers of the disease. We administered the Brief Smell Identification Test (BSIT) to 471 older people without dementia or cognitive impairment who then completed annual clinical evaluations and brain autopsy at death. BSIT score was associated with more rapid decline in episodic memory and with increased risk of developing incident mild cognitive impairment (MCI), even after controlling for baseline level of episodic memory and possession of an apolipoprotein E epsilon4 allele. In 34 people who died without evidence of cognitive impairment, lower BSIT score was associated with higher level of AD pathology, even after controlling for epsilon4 and for level of episodic memory function when olfaction was assessed. These analyses suggest that among older people without clinical manifestations of AD or MCI, olfactory dysfunction is related to both the level of AD pathology in the brain and the risk of subsequently developing prodromal symptoms of the disease, and that these associations persist after accounting for the effects of other recognized behavioral and genetic markers of the disease.