The first quick olfactory test specific for Alzheimer's disease and French culture.

PURPOSE: Olfactory identification disorder is considered a promising early biomarker of Alzheimer's disease (AD). The QUICK TODA2 can be used as a short olfactory screening tool specific for French AD patients. The selection of AD specific odorants and the design of this screening were the main objectives of this twofold study. METHODS: In study 1, the TODA2 olfactory test was administered to 43 mild-AD patients and 45 healthy controls (HC) in five memory centres in France. The selection of AD specific odorants was based on the differences in the proportion of correct answers and in the threshold means between AD and HC groups. In study 2, another set of 19 mild-AD patient were included at the memory centre of Nice Hospital. All participants completed the olfactory assessment pipeline including the QUICK TODA2, TODA2 and Sniffin' Sticks Identification sub-Test (SST-i). The individual scores of the three tests were correlated. RESULTS: In study 1, ten TODA2 odorants could significantly differentiate AD participants from controls. We selected the six most AD-sensitive items to design the QUICK TODA2. In study 2, we reported strong significant correlations between QUICK TODA2 and TODA2 (ρ(17) = 0.68, p = 0.001**), SST-i and QUICK TODA2 (ρ(17) = 0.65, p = 0.002**), SST-i and TODA2 (ρ(17) = 0.57, p = 0.01*). CONCLUSION:  QUICK TODA2 is a 5-min non-invasive olfactory AD screening tool dedicated to French culture. Its results converge with those of longer, validated olfactory tests. It could be used as a quick screening tool in the general daily practice before an extensive assessment in memory centres.

Differences in olfactory dysfunction and its relationship with cognitive function in schizophrenia patients with and without auditory verbal hallucinations.

Olfactory discrimination dysfunction has been observed in patients with schizophrenia (SCZ), but its relationship with cognitive function has not been clarified. The purpose of this study was to examine the differences in olfactory identification function in SCZ patients with and without auditory verbal hallucinations (AVHs) and its relationship with cognitive function. Olfactory identification function was measured in 80 SCZ patients with AVHs, 57 SCZ patients without AVHs, and 87 healthy controls (HC). Clinical symptom scores and neuropsychological measures were also administered to all corresponding subjects. Compared to HC, SCZ patients showed significant deficits in olfactory identification and cognitive function, but there were no differences in olfactory identification dysfunction and cognitive dysfunction between the two subgroups. In the non-AVHs subgroup only, poorer Olfactory Stick Identification Test for Japanese (OSIT-J) scores were significantly and positively correlated with total and delayed recall (Bonferroni correction, p < 0.002). Stepwise regression analysis revealed that factors affecting olfactory identification impairment differed in the two SCZ patient subgroups. In conclusion, this study highlights the commonality of olfactory identification dysfunction in SCZ patients and the importance of olfactory assessment of different subtypes of SCZ patients.

Comparison of olfactory function, cognitive function and serum tumor necrosis factor-α between bipolar and schizophrenic patients in the remission stage.

OBJECTIVES: Olfactory function, serum tumor necrosis factor-α (TNF-α) and cognitive function were compared between bipolar disorder (BD) and schizophrenia (SP) patients in the remission stage combined with correlation analysis, with the aim of identifying new indicators for the auxiliary diagnosis of these psychiatric illnesses. METHODS: A total of 46 euthymic BD patients, 42 clinically stable SP patients and 42 healthy controls (HC) were included in this study. Olfactory sensitivity (OS) and olfactory identification (OI) were assessed using Sniffin' Sticks test, and serum TNF-α levels were measured by ELISA. Clinical symptoms were evaluated with the Hamilton Rating Scale for Depression, Young Mania Rating Scale, Hamilton anxiety scale, and the Positive and Negative Syndrome Scale (PANSS). Social function was evaluated with the Global Assessment Function (GAF) scale. Cognitive function was evaluated using the Trail Making Test-A (TMT-A) and Digit Cancellation Test (DCT). RESULTS: OI and cognitive function scores and serum TNF-α levels were significantly lower in the BD and SP patients compared with the HC participants. There was no significant difference between the BD and SP groups, and there were no significant differences in OS among the three groups. OI score was positively correlated with years of education in both the BD and SP groups. OI score in the SP group was negatively correlated with age and PANSS score, and positively correlated with GAF score. In the BD group, OS was positively correlated with DCT II and DCT III. In the SP group, OS and OI scores were positively correlated with DCT III, and negatively correlated with TMT-A time. Furthermore, there was a positive correlation between TNF-α and DCT II in the BD group. There was no significant linear correlation between olfactory function and TNF-α in the BD or SP group. CONCLUSION: OI may be a trait marker for BD and SP. Some cognitive functions may be correlated not only with TNF-α in BD patients in remission, but also with olfactory function in BD and SP patients in remission.

Changes in olfactory identification function in total laryngectomy patients - A retrospective study focusing on nasal airflow-inducing maneuver usage, Open Essence misreactions, and odor cluster.

PURPOSE: We aimed to examine how the olfactory identification function of laryngectomy patients is altered by nasal airflow-inducing maneuver (NAIM), a method of olfactory rehabilitation, by analyzing incorrect and correct responses to olfactory identification tests to achieve odor classification. METHODS: Olfactory identification test (Open Essence [OE]) was administered to 46 patients who had undergone a total laryngectomy [Start group (NAIM was initiated from this study) = 17; (already) Using group = 19; and Nonuse group = 10]. The tests were immediately performed after the NAIM and after a mean duration of 8 months. RESULTS: In the Start group, changes in OE correct and incorrect responses showed a significant increase and decrease in the number of correct (p < 0.01) and "detectable but not recognizable" responses (p < 0.05), respectively. In the Using group, errors related to "same cluster" and "detectable but not recognizable" increased and decreased significantly (p < 0.05), respectively. The Nonuse group showed a trend of demonstrating a relatively lower number of correct responses (p < 0.1). Results of odor classification showed that only "putrefaction and sulfur" did not have any significant positive responses in the Start group. DISCUSSION: Evidently, the possibility of capturing changes in olfactory identification function by performing a false response analysis was observed, even if recovery appears to have stalled after long-term use of NAIM. Furthermore, including the "putrefaction and sulfur" cluster in the olfactory rehabilitation of laryngectomy patients and teaching them to consciously sniff "putrefaction and sulfur" in their daily lives is necessary.

Metal-containing Particulate Matter and Associated Reduced Olfactory Identification Ability in Children from an Area of High Atmospheric Exposure in Mexico City.

Air pollution has been linked to poor olfactory function in human adults. Among pollutants, particulate matter (PM) is especially relevant, as it may contain toxic metal ions that can reach the brain via olfactory pathways. Our purpose was to investigate the relation between atmospheric PM and olfactory identification performance in children. Using a validated method, we tested the olfactory identification performance of 120 children, 6-12 years old, from two locations in Mexico City: a focal group (n = 60) from a region with high PM levels and a control group of equal size and similar socioeconomic level from a region with markedly lower PM concentrations. Groups were matched for age and sex. Concentrations of manganese and lead in the hair of participants were determined as biomarkers of exposure. Daily outdoor PM levels were obtained from official records, and indoor PM levels were measured in the children's classrooms. Official records confirmed higher levels of outdoor PM in the focal region during the days of testing. We also found higher classroom PM concentrations at the focal site. Children from the focal site had on average significantly lower olfactory identification scores than controls, and hair analysis showed significantly higher levels of manganese for the focal children but no difference in lead. Children appear to be vulnerable to the effects of air pollution on olfactory identification performance, and metal-containing particles likely play a role in this. Olfactory tests provide a sensitive, noninvasive means to assess central nervous function in populations facing poor air quality.

Inability to Smell Peppermint Is Related to Cognitive Decline: A Prospective Community-Based Study.

BACKGROUND: A few studies have demonstrated the association of poorer olfactory identification (OI) with poorer cognition in population-based cohorts. None of them considered the outcome associated with the inability to smell a certain odor. OBJECTIVE: To verify the hypothesis that at least one specific odor is associated with incident cognitive decline among older adults. METHODS: In the Shanghai Aging Study, a sub-cohort of 948 dementia-free participants who had baseline OI measurements were prospectively followed for 5 years. RESULTS: An inability to smell peppermint (ß = -0.44, p < 0.001), rose (ß = -0.14, p = 0.040), or coffee (ß = -0.37, p = 0.002) was inversely related to the annual rate of change in the Mini Mental State Examination score, and an inability to smell peppermint was associated with a higher risk for incident dementia (hazard ratio 2.67, 95% CI 1.44-4.96) after adjustment for confounders. CONCLUSION: Our study suggests that some odors, especially peppermint, might be considered as a potential predictor for dementia in older populations.

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging.

OBJECTIVES: To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. DESIGN: Prospective multicenter cross-sectional study with a longitudinal arm. SETTING: Outpatient memory diagnostic clinics in New York and Texas. PARTICIPANTS: Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. MEASUREMENTS: Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. RESULTS: For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. CONCLUSIONS: Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals.

Combining olfactory test and motion analysis sensors in Parkinson's disease preclinical diagnosis: a pilot study.

OBJECTIVES: Preclinical diagnosis of Parkinson's disease (PD) is nowadays a topic of interest as the neuropathological process could begin years before the appearance of motor symptoms. Several symptoms, among them hyposmia, could precede motor features in PD. In the preclinical phase of PD, a subclinical reduction in motor skills is highly likely. In this pilot study, we investigate a step-by-step method to achieve preclinical PD diagnosis. MATERIAL AND METHODS: We used the IOIT (Italian Olfactory Identification Test) to screen a population of healthy subjects. We identified 20 subjects with idiopathic hyposmia. Hyposmic subjects underwent an evaluation of motor skills, at baseline and after 1 year, using motion analysis sensors previously created by us. RESULTS: One subject showed significant worsening in motor measurements. In this subject, we further conducted a dopaminergic challenge test monitored with the same sensors and, finally, he underwent [123 I]-FP/CIT (DaTscan) SPECT brain imaging. The results show that he is probably affected by preclinical PD. CONCLUSIONS: Our pilot study suggests that the combined use of an olfactory test and motor sensors for motion analysis could be useful for a screening of healthy subjects to identify those at a high risk of developing PD.

Association between olfactory identification and cognitive function in community-dwelling elderly: the Shanghai aging study.

BACKGROUND: The smell sense reduction was considered to represent the potentially warning of early stage of neurodegenerative disorders. The Shanghai Aging Study provided us a unique opportunity to explore the association between olfactory identification (OI) and cognitive function among community-dwelling elderly in China. METHODS: OI of each participant was measured by the 12-item identification tests from Sniffin' Sticks Screening test (SSST-12). Participants with mild cognitive impairment (MCI) were diagnosed by Petersen criteria. We used the logistic regression analysis to explore the association between OI scores and cognitive function by adjusting potential confounders. RESULTS: Among 1782 non-demented participants, 345 (19.4 %) participants were diagnosed as MCI. The mean OI score for participants with MCI [7.1 (SD 2.3)] was significantly lower than that for those with normal cognition [8.2 (SD 2.0), P < 0.0001]. After adjusted for age, gender, education, lifestyles, medical history, Apolipoprotein E genotype, lower OI score was found to be an independent influence factor related to MCI (OR 1.19, 95 % CI 1.11-1.27). CONCLUSIONS: Our study suggests that poor OI may be associated with MCI in elderly population. Further prospective studies may confirm the OI as a reliable and early marker predicting the decline of cognitive function.

Olfactory identification and cognitive performance in community-dwelling older adults with mild cognitive impairment.

Olfactory impairment constitutes one of the earliest signs of Alzheimer's disease in older adults with mild cognitive impairment. We investigated which aspects of neuropsychological measures are correlated with olfactory identification performance among older adults with mild cognitive impairment. Total of 220 participants with mild cognitive impairment (mean age 71.7 years) were examined. Odor identification was assessed using the Open Essence test. Participants underwent comprehensive neurocognitive evaluation, including measures of verbal memory, visual memory, working memory, attention/executive function, and processing speed. We examined associations between olfactory function and cognitive performance scores. Participants with severe hyposmia exhibited significantly poor verbal and visual memory performance, attention/executive function, and slower processing speed scores compared with those without severe hyposmia. In multivariable logistic regression models, better performance scores on verbal and visual memory were significantly associated with decreased likelihood of severe hyposmia after adjusting for age, sex, education, and other cognitive performance scores. These findings suggest that olfactory impairment might be more closely associated with memory loss compared with other aspects of cognitive functioning in mild cognitive impairment subjects.

Serum TRPA1 mediates the association between olfactory function and cognitive function.

Background: Olfactory dysfunction was associated with poorer cognition. However, the association between transient receptor potential cation channel subfamily A member 1 (TRPA1) and cognitive function have not been studied. This study aimed to evaluate the mediation effect of TRPA1 on the association between olfactory and cognitive function among Chinese older adults. Methods: We recruited 121 participants with cognitive impairment (CI) and 135 participants with normal cognition (NC) from a memory clinic and the "Shanghai Aging Study." Olfactory identification of each participant was measured by the Sniffin' Sticks Screening Test 12 (SSST-12). Serum TRPA1 were quantified using the Enzyme-Linked Immunosorbent Assay. The mediation effects of TRPA1 on the association between olfactory function and cognitive function were explored using mediation analysis. Results: The CI group had a significantly higher proportion of the high level of serum TRPA1 (58.7%) than the NC group (42.2%) (p = 0.0086). After adjusted for gender, age, and years of education, mediation analysis verified that TRPA1 partially mediated the association between SSST-12 and Mini Mental State Examination (MMSE). It also verified that TRPA1 partially mediated the association between the identification of peppermint and MMSE. Conclusion: Our study emphasizes the mediation role of TRPA1 in the relationship between olfactory and cognitive function among older adults. Further research is necessary to explore the mechanism of TRPA1 on the relationship between olfactory and cognitive decline.

Corrigendum: Serum TRPA1 mediates the association between olfactory function and cognitive function.

[This corrects the article DOI: 10.3389/fnagi.2024.1411031.].

Relationship between olfactory and gustatory functions: The Iwaki health promotion project 2019.

OBJECTIVE: Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population. METHODS: We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating. RESULTS: Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women. CONCLUSION: These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention.

A multi-environmental source approach to explore associations between metals exposure and olfactory identification among school-age children residing in northern Italy.

BACKGROUND: Metal exposures can adversely impact olfactory function. Few studies have examined this association in children. Further, metal exposure occurs as a mixture, yet previous studies of metal-associated olfactory dysfunction only examined individual metals. Preventing olfactory dysfunctions can improve quality of life and prevent neurodegenerative diseases with long-term health implications. OBJECTIVE: We aimed to test the association between exposure to a mixture of 12 metals measured in environmental sources and olfactory function among children and adolescents residing in the industrialized province of Brescia, Italy. METHODS: We enrolled 130 children between 6 and 13 years old (51.5% females) and used the "Sniffin' Sticks" test to measure olfactory performance in identifying smells. We used a portable X-ray fluorescence instrument to determine concentrations of metals (arsenic (As), calcium, cadmium (Cd), chromium, copper, iron, manganese, lead (Pb), antimony, titanium, vanadium and zinc) in outdoor and indoor deposited dust and soil samples collected from participants' households. We used an extension of weighted quantile sum (WQS) regression to test the association between exposure to metal mixtures in multiple environmental media and olfactory function adjusting for age, sex, socio-economic status, intelligence quotient and parents' smoking status. RESULTS: A higher multi-source mixture was significantly associated with a reduced Sniffin' Sticks identification score (ß = -0.228; 95% CI -0.433, -0.020). Indoor dust concentrations of Pb, Cd and As provided the strongest contributions to this association (13.8%, 13.3% and 10.1%, respectively). The metal mixture in indoor dust contributed more (for 8 metals out of 12) to the association between metals and olfactory function compared to soil or outdoor dust. IMPACT STATEMENT: Among a mixture of 12 metals measured in three different environmental sources (soil, outdoor and indoor dust), we identified Pb, Cd and As measured in indoor dust as the main contributors to reduced olfactory function in children and adolescents residing in an industrialized area. Exposure to indoor pollution can be effectively reduced through individual and public health interventions allowing to prevent the deterioration of olfactory functions. Moreover, the identification of the factors that can deteriorate olfactory functions can be a helpful instrument to improve quality of life and prevent neurodegenerative diseases as long-term health implications.

Correlation Between Cortical Thickness Abnormalities of the Olfactory Sulcus and Olfactory Identification Disorder and Persistent Auditory Verbal Hallucinations in Chinese Patients With Chronic Schizophrenia.

BACKGROUND AND HYPOTHESIS: Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. STUDY DESIGN: In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. STUDY RESULTS: Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction). CONCLUSIONS: Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients.

Significant improvements in the olfactory sensitivity of bipolar I disorder patients during euthymia versus manic episodes: a longitudinal study.

Introduction: Research has indicated that individuals diagnosed with bipolar disorder (BD) might experience alterations in their olfaction or levels of serum tumor necrosis factor-α (TNF-α), but no studies have investigated olfactory function and serum TNF-α in BD patients simultaneously. Moreover, there is a lack of existing research that compares the longitudinal olfactory function between individuals with manic and euthymic BD I. Methods: Patients with manic BD I (BDM, n=44) and healthy controls (HCs, n=32) were evaluated symptoms (measured via the Young Manic Rating Scale, YRMS), social function (measured via the Global Assessment Function, GAF), serum TNF-α, and olfactory function (via the Sniffin' Sticks test) including olfactory sensitivity (OS) and olfactory identification (OI). The BDM patients were followed up to the remission period and re-evaluated again. We compared OS, OI and serum TNF-α in manic and euthymic patients with BD I and HCs. We examined the correlation between olfactory function and symptoms, social function, and serum TNF-α in patients with BD I. Results: The BDM patients exhibited significantly lower OS and OI compared to the HCs (Z = -2.235, P = 0.025; t = -6.005, P < 0.001), while a positive correlation was observed between OS and GAF score (r = 0.313, P = 0.039). The OS in the BD I remission group (n=25) exhibited significantly superior performance compared to the BDM group (t = -4.056, P < 0.001), and the same as that in the HCs (P = 0.503). The change in OS showed a positive correlation with the decrease in YMRS score (r = 0.445, P = 0.026), and a negative correlation with the course of disease (r = -0.594, P = 0.002). The TNF-α in BD I patients was significantly lower compared to HCs (P < 0.001), and not significantly correlated with olfactory function (all P > 0.05). Conclusion: The findings suggest that OS and OI are impaired in BDM patients, and the impaired OS in those patients can be recovered in the remission stage. OI may serve as a potential characteristic marker of BD. OS might be useful as an index for BDM treatment efficacy and prognosis.

Impairment of olfactory identification ability in ultra-high risk for psychosis and drug-naïve first episode psychosis.

OBJECTIVE: Patients with psychotic diseases have been reported to exhibit abnormalities in their olfactory discrimination. These alterations have also been identified in people at high genetic or clinical risk for psychosis, suggesting olfactory discrimination dysfunction may be a potential risk factor for developing psychosis. Thus, the purpose of our study is to explore the difference in olfactory discrimination ability in the prosal stage and early stage of psychosis and to explore the potential risk factor of developed psychosis. METHODS: We compared olfactory identification and cognitive function in 89 ultra-high-risk (UHR) individuals, 103 individuals with Drug-naïve first-episode schizophrenia (FES), 81 genetic high-risk (GHR) individuals, and 97 healthy controls (HC). Additionally, we compared olfactory identification and cognitive function between two groups; UHR individuals who later transitioned to psychosis (UHR-T; n = 33) and those who did not transition (UHR-NT; n = 42)). Furthermore, we analyzed the correlations between olfactory discrimination ability and cognitive function and symptoms and compared the olfactory function between men and women. RESULTS: Patients with first-episode schizophrenia (FES) and those at ultra-high risk (UHR) for psychosis exhibited more significant deficits in olfactory identification than healthy controls (HC), while no differences in olfactory identification dysfunction were observed between the genetic high risk (GHR) and HC groups. Notably, individuals in the UHR group who later developed psyhchosis displayed a steeper marked decline in their baseline olfactory identification ability than that of those in the UHR group who did not develop psychosis. Cognitive dysfunction is widely observed in both the FES and UHR groups, with a distinct correlation identified between olfactory discrimination function and cognitive performance. Finally, overall, women exhibit significantly superior olfactory function than men. CONCLUSION: In conclusion, these findings suggest that impairment of olfactory identification exists in the early stage of psychosis. Olfactory identification dysfunction may therefore be a potential marker of predicting the transition to schizophrenia.

Trajectories of olfactory identification preceding incident mild cognitive impairment and dementia: a longitudinal study.

BACKGROUND: The pattern of olfactory identification change in the early phases of dementing disorders is unclear. We aimed to assess olfactory identification trajectories preceding incident mild cognitive impairment (MCI) and dementia and explore the role of brain pathologies in these trajectories. METHODS: Within the Rush Memory and Aging Project, 1318 dementia-free older adults were followed annually for up to 11 years. Olfactory identification was assessed using the Brief Smell Identification Test annually. Of 900 cognitively intact participants, incident MCI and dementia were diagnosed following standard criteria. Over follow-up, 518 participants died and underwent brain autopsies for neuropathological assessment. Data were analyzed using mixed-effect models with backward timescales. FINDINGS: Compared to participants who remained cognitively intact, olfactory identification declined faster among those who developed MCI (ß -0.09 [95% CI -0.13, -0.05]), leading to a significantly lower olfactory identification starting from five years preceding MCI diagnosis (mean difference at year -5: -0.39 [-0.71, -0.07]). Among participants with incident MCI, olfactory identification declined faster in those who developed dementia compared to those who did not (ß -0.19 [-0.36, -0.01]), leading to a significantly lower olfactory identification starting from three years preceding dementia diagnosis (mean difference at year -3: -0.95 [-1.67, -0.23]). A faster decline in olfactory identification was associated with higher burdens of global Alzheimer's disease pathology, neurofibrillary tangles, and amyloid beta load. INTERPRETATION: Olfactory identification declined faster preceding dementia disorders and Alzheimer's pathology may underlie these faster declines. FUNDING: This study was funded by the National Institutes of Health (R01AG17917) and Swedish Research Council (2021-01647).

Impaired olfactory function in bipolar disorder patients during acute episodes regardless of psychotic symptoms.

Background: The aim of this study was to analyze whether the presence of psychotic symptoms affects olfactory function in patients with bipolar disorder (BD). We also compared olfactory function between the period of episode and remission in patients with BD. Methods: BD patients in the acute phase were tracked to the remission stage. The psychiatric symptoms and social function of the enrolled subjects were assessed using the Hamilton Rating Scale for Depression (HAMD), the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Anxiety (HAMA), the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment Function (GAF). Olfactory sensitivity (OS) and olfactory identification (OI) was assessed using the Sniffin' Sticks test. Differences in OS and OI among the episodic group, the euthymic group, and the healthy control (HC) group were compared. According to whether BD is accompanied by psychotic symptoms, the OS and OI in the BD with psychotic symptoms group (P-BD), the BD without psychotic symptoms group (NP-BD), and the HC group were compared. Results: The P-BD and NP-BD groups exhibited impaired OI compared with the HC group, but there was no significant difference in OI between the P-BD and NP-BD groups, or in OS among all three groups. All patients with episodic BD had significantly lower OS and OI compared with the HC group. OI in euthymic BD patients was still impaired; however, OS recovered, showing no significant difference compared with that in the HC group. Conclusion: The results indicate that patients with episodic BD have impaired OS and OI, regardless of psychotic symptoms. OI may be a characteristic marker of BD, and OS may be a state marker that can be used to distinguish between episodic and euthymic BD.

Variations in olfactory function among bipolar disorder patients with different episodes and subtypes.

Purpose: Most studies on olfactory function in individuals with bipolar disorder (BD) have not distinguished between the different subtypes or between the acute phase (mania or depression) and euthymic state. In this study, we compared olfactory function among BD patients with different subtypes and episodes to explore the potential use of olfactory function as a biomarker for the early identification of BD. Patients and methods: The study sample consisted of 117 BD patients who were hospitalized between April 2019 and June 2019, and 47 healthy volunteers as controls. The BD patients were divided into a bipolar I disorder (BD I) (n = 86) and bipolar II disorder (BD II) group (n = 31) according to the different subtypes, and divided into depressive BD (n = 36), manic BD (n = 44), or euthymic BD (n = 37) groups according to the types of episodes they experienced. We assessed olfactory sensitivity (OS) and olfactory identification (OI) via the Sniffin' Sticks test and used the Hamilton Depression Rating Scale (HAMD) and Young Manic Rating Scale (YMRS) to evaluate BD characteristics among all subjects. Results: Compared with controls, the participants with BD showed decreased OS and OI. We found statistically significant differences in OS and OI between the BD I group and controls, as well as differences in OS between the BD I and BD II group. Least-significant difference multiple comparisons revealed statistically significant differences in OS between the depressive BD group, manic BD group and controls and also between the manic BD and euthymic BD group. OI was positively correlated with the YMRS score in the BD I group and OS was negatively correlated with the HAMD score in the BD II group. Conclusion: This may be the first study to compare olfactory function in patients with BD I vs. BD II via pairwise comparisons. Our findings suggest that OS may have potential as a biomarker for distinguishing the different subtypes of BD and as a state-related biomarker for differentiating the acute phase from the euthymic state of BD. However, further prospective research is warranted.