Human olfaction : Associations with longitudinal assessment of episodic memory, dementia, and mortality risk

Sammanfattning: A declining sense of smell is a common feature in older age. Above and beyond diminished smelling capacity due to normal processes of human aging, impairments in olfactory function have also been linked to numerous ill-health related outcomes, such as cognitive dysfunctions, dementia pathology and even an increased risk of death. Based on population-based data from the Swedish Betula Prospective Cohort Study, the aim of this thesis was to further our understanding regarding the role of olfaction in long-term memory decline, dementia, and mortality. Furthermore, this thesis investigated the predictive utility of self-reported olfactory dysfunction for assessing the risk of conversion to later dementia and to mortality, as well as the predictive utility of long-term subjective olfactory decline for an actual long-term decline in odor function. Study I explored associations of olfactory deficits with memory decline and found that impairments in an odor identification test were related to an ongoing and long-term decline in episodic memory only in carriers of the e4 allele of the Apolipoprotein E, a genetic risk factor for Alzheimer’s disease. Study II investigated the predictive utility of olfactory ability for conversion to common forms of dementia in participants with intact baseline cognition during a follow-up time-span of 10 years. The results showed that lower odor identification scores, as well as subjectively assessed odor impairment, were associated with an increased risk for dementia conversion, and that the effects of objective and subjective odor function were cumulative. Study III investigated whether olfactory ability could predict mortality and showed that lower odor identification scores, as well as subjective odor impairments, were associated with an elevated risk of death within a follow-up time-span of approximately 10 years. Crucially, this effect could not be explained by dementia conversion prior to death. Study IV showed that a subjectively assessed long-term and ongoing olfactory decline was predictive of an objectively assessed long-term and ongoing decline in odor function. Subjective olfactory impairments might thus be indicative of an actual olfactory decline in older adults. Overall, the findings of this thesis indicate that sense of smell is closely related to processes of memory decline and dementia as well as mortality in older adults. Furthermore, the results of these investigations shed a new light on the role of subjectively experienced olfactory decline, which might reflect an actual intra-individual change in olfactory ability in older adults.