Type of study: Cohort study

The finding: A prospective study following elderly patients found that olfactory deficits (hyposmia and anosmia) predicted subsequent faster rate of cognitive decline across multiple domains (including a global composite, as well as episodic memory, visuospatial ability, perceptual speed, and semantic memory), with global cognitive composite score and episodic memory remaining significant when repeating the analyses after having excluded incident dementia cases during the study.  In addition, olfactory dysfunction was associated with lower hippocampal volume. 

Strength and weaknesses: The major strength of this study is its prospective design and duration of follow up, with mean follow up duration of 9 years, with the study including only non-demented subjects and finding significant associations between olfactory dysfunction and memory even after excluding incident dementia cases from the analyses. In addition, the authors performed comprehensive neuropsychological batteries targeting multiple areas of cognition.

The weaknesses of this study include the variable duration of follow up between different subjects, with a range from 1-15 yrs.  Another weakness is the lack of prospective imaging; the MRI data was obtained in cross-sectional fashion and apparently without any planned temporal relationship with study enrolment.  It is therefore difficult to draw conclusions from the association between olfactory impairment and medial temporal lobe volumes.

Relevance: The relationship between olfactory dysfunction and dementia, specifically AD (and, of course, parkinsonian disorders) has received increasing attention as a potential predictor of dementia in healthy subjects (or, identification of preclinical dementia). However, the relationship remains unclear and evidence to date is mixed.  That the (mean) duration of follow up and comprehensiveness of cognitive batteries obtained during the study were both significantly greater than most existing studies on the subject does offer the reader a compelling argument that olfactory dysfunction does appear to be related to cognitive decline, independent of numerous other risk factors.  While we are certainly a long way from concluding that olfactory deficits can predict dementia, this study adds to the body of literature suggesting that olfactory function is an area in need of future research, as identification of preclinical dementia is an area of significant clinical concern.