APOE-ɛ4 effects on longitudinal decline in olfactory and non-olfactory cognitive abilities in middle-aged and old adults

Characterizing aging-related decline trajectories in mental abilities, and relationships of the ɛ4 allele of the Apolipoprotein gene, helps to identify individuals at high risk for dementia. However, longitudinal changes in olfactory and non-olfactory cognitive abilities have not been investigated in relation to the ɛ4 allele. In the present study, participants from a large population-based study (657 middle-aged and 556 old) were tested over 10 years on their performance on an odor identification task and three non-olfactory cognitive tasks; MMSE, episodic memory, and semantic memory. Our key finding is that in middle-aged participants, odor identification declined twice as fast for ɛ4/4 homozygotes, compared to non-carriers. However, in old participants, the ɛ4/4 homozygotes showed an impaired odor identification ability, but they declined at a similar rate as the non-carriers. Furthermore, in old participants all assessments displayed aging-related declines, but exaggerated declines in ɛ4-carriers were found only in MMSE and episodic memory assessments. In sum, we present evidence that odor identification ability starts to decline already in middle-aged, and that carriers of ɛ4/4, who are at highest risk of developing dementia, decline twice as fast. Our results may have implications for use of odor identification assessment in detection of early-stage dementia.