Olfactory dysfunction and depression are common in later life, and both have been presented as risk factors for dementia. Our purpose was to investigate the associations between these two risk factors and determine if they had an additive effect on dementia risk.

Olfactory function was assessed using the Brief Smell Identification Test (BSIT), and depression was classified using a combination of the 15-item Geriatric Depression Scale (GDS) score and current antidepressant use. Cross-sectional associations between depression and olfactory function were examined using correlations. Cox regression analyses were conducted to examine the longitudinal relationship between olfaction and depression and incident dementia across 12-years of follow-up.

Participants were 780 older adults (aged 70–90 years; 56.5% female) from the Sydney Memory and Ageing Study (MAS) without a diagnosis of dementia at baseline.

Partial correlation revealed a nonsignificant association between baseline depression and olfactory function after accounting for covariates (r = −.051, p = .173). Cox regression showed that depression at baseline (hazard ratio = 1.706, 95% CI 1.185–2.456, p = .004) and lower BSIT scores (HR = .845, 95%CI .789–.905, p < .001) were independently associated with a higher risk of incident dementia across 12 years. Entering both predictors together improved the overall predictive power of the model.

Lower olfactory identification scores and depressive symptoms predict incident dementia over 12 years. The use of BSIT scores and depression in conjunction provides a greater ability to predict dementia than either used alone. Assessment of olfactory function and depression screening may provide clinical utility in the early detection of dementia.

The relationship between the olfactory system and emotional processing is an area of growing interest in schizophrenia research. Both the orbitofrontal cortex and amygdala are involved in the processing of olfactory information, and olfactory deficits may be also influenced by endogenous opioids and calcitonin gene-related peptide (CGRP), which is probably involved in dopaminergic transmission. However, the relationship between endorphins and dopaminergic transmission has not been fully explored.

Odor identification performance and valence interaction was evaluated among 50 schizophrenic patients and 50 controls. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). All study participants were subjected to the University of Pennsylvania Smell Identification Test (UPSIT), blood β-endorphin (BE) and CGRP measurement.

Insignificantly higher BE concentrations were observed in the patient group, while significantly higher UPSIT scores were seen in controls (mean UPSIT 32.48 vs 26.82). The patients demonstrated significantly more identification errors for pleasant (P = 0.000) and neutral (P = 0.055) odors than for unpleasant odors. Patients with higher BE concentrations made more identification errors concerning pleasant (Rs = −0.292; P = 0.04) and neutral odors (Rs = −0.331; P = 0.019). Although the concentration of CGRP was significantly higher in the patient sample (P < 0.001), no relationship was observed between concentration and UPSIT performance. A strong negative correlation was observed between PANSS N score and UPSIT total score (Rs = −0.646; P = 0.000), between PANSS N score and identification by valence for pleasant and neutral odors (UPSIT n/16: Rs = −0.450, P = 0.001; UPSIT n/15: Rs = −0.586, P = 0.000), and a weak negative correlation between PANSS N score and identification of unpleasant odors (UPSIT n/9: Rs = −0.325, P = 0.021).

Schizophrenic patients present a unique pattern of smell identification characterized by aberrant hedonic ratings for pleasant odors but not unpleasant ones. Individuals with predominant negative symptoms and higher BE concentrations are most able to identify negative odors.