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This is a cross-sectional and longitudinal study to establish diagnostic models based on olfactory function assessments and odor-induced brain activation for cognitive impairment in patients with type 2 diabetes mellitus.
Patients with diabetes have increased risks of cognitive impairment and dementia, which affecting the quality of life and diabetes management. Therefore, it is an urgent challenge to identify non-invasive biomarkers for early diagnosis and prognosis of the cognitive decline in patients with diabetes. Previous research has shown that both olfactory dysfunction and decreased odor-induced brain activation are present before clinically measurable cognitive decrements in type 2 diabetes. This is a cross-sectional and longitudinal study to establish diagnostic models based on olfactory function assessments and odor-induced brain activation for cognitive impairment in patients with type 2 diabetes mellitus. The investigators will recruit 200 patients with type 2 diabetes in the outpatient and inpatient departments. Health controls will be recruited from the community. At the baseline, clinical information collection, 100g-steamed bread meal test, biochemical measurement, cognitive assessments, olfactory test and functional magnetic resonance imaging(fMRI) scan will be conducted for all participants. Study duration was 3 years with a follow-up every 18 months. In the longitudinal study, all of the assessments will be repeated to evaluate changes of observational parameters.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Type 2 Diabetes Mellitus | These patients must have a definite diagnosis of type 2 diabetes mellitus (T2DM) according to the American Diabetes Association (ADA) standards. Some of these patients have symptoms of cognitive impairment, while others have normal cognition. All T2DM patients will undergo physical exam, cognitive and olfactory test as well as structural and brain functional MRI at baseline and follow-up time points. |
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| Healthy Control | These participants have normal glucose tolerance and normal cognition. All HC subjects will undergo physical exam, cognitive and olfactory test as well as structural and brain functional MRI at baseline and follow-up time points. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cognitive assessments | Behavioral | Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Rey Auditory Verbal Learning Test (RAVLT), Boston Naming Test (BNT), Digit Span Test (DST), Trail Making Test (TMT). |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline cognitive performance | The Montreal Cognitive Assessment (MoCA) score, ranges from 0 to 30, and higher scores mean better cognition. | Day 1 of entry study |
| Baseline olfactory threshold | Olfactory threshold test: score range 1-13.5, which is determined based on a series of binary dilutions of the N-butanol solution in light mineral oil. The higher the score is, the more sensitive the participant is in detecting an odor. Scores of 8-10 were considered normal olfactory sensitivity, whereas scores of 1-3 signified olfactory dysfunction or anosmia, and scores of ≥10 indicate better olfactory sensitivity. | Day 1 of entry study |
| Baseline olfactory memory | Olfactory memory test: Part A: Participants are shown 4 pictures for each odor (10 odors in total), then they need to select what they sniffed. Have a 10-minute break. Part B: Participants sniff 20 different odors, 10 of which are the same odors as in Part A. They need to select the picture and figure out whether the odor is old or new. | Day 1 of entry study |
| Baseline odor-induced brain fMRI activation | Each participant underwent a series of task fMRI scans to measure temporal brain response to four increasing concentrations of lavender odors (0.032%, 0.10%, 0.32%, and 1.0) diluted in 1,2-propanediol (Sigma-Aldrich, St. Louis, MO). The visual cues of "+" and "smell" were used for baseline and odor stimulation, respectively. Each concentration was assessed three times, with fresh air and scent occurring alternately. Participants were instructed to press a button once they smelled the lavender scent. A general linear model was used to estimate odor-induced brain activation. Contrasts between "fresh air > rest" and "scent > rest" for each participant were made to get odor-induced brain activation value. Bilateral parahippocampus, amygdala, piriform cortex, insula, orbitofrontal cortex, entorhinal cortex, and hippocampus were extracted and merged as olfactory regions of interest (ROIs) for further analyses. |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline brain structural MRI scan | Cortical morphology | Within 1 week after cognitive assessments |
| Baseline brain functional MRI scan | Large-scale network functional connectivity |
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Inclusion Criteria:
Exclusion Criteria:
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T2DM patients will be recruited from the outpatient and inpatient units of the endocrinology department of the investigator's hospital. Healthy control will be recruited in the community.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wen Zhang, MD, PhD | Contact | 86-15950576908 | zw7830254@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Radiology, the Affiliated Drum Tower Hospital of Nanjing University | Recruiting | Nanjing | Jiangsu | 210008 | China |
IPD sharing will be made during the 12 months after the end of study, and the original data can be obtained from the PI if necessary.
during the 12 months after the end of study
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| Olfactory function measurements | Other | Olfactory Threshold, Odor Identification Score, Odor Memory Score. |
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| Functional magnetic resonance imaging | Other | resting-state fMRI, odor-induced fMRI. |
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| Within 1 week after cognitive assessments |
| Longitudinal changes of cognitive performance | Compare the change of MoCA score from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up). The Montreal Cognitive Assessment (MoCA) score, ranges from 0 to 30, and higher scores mean better cognition. | From baseline to 18 months' follow-up and 36 months' follow-up |
| Longitudinal changes of olfactory threshold | Compare the change of olfactory threshold tests score from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up). Olfactory threshold test: score range 1-13.5, which is determined based on a series of binary dilutions of the N-butanol solution in light mineral oil. The higher the score is, the more sensitive the participant is in detecting an odor. Scores of 8-10 were considered normal olfactory sensitivity, whereas scores of 1-3 signified olfactory dysfunction or anosmia, and scores of ≥10 indicate better olfactory sensitivity. | From baseline to 18 months' follow-up and 36 months' follow-up |
| Longitudinal changes of olfactory memory | Compare the change of olfactory memory tests score from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up). Olfactory memory test: Part A: Participants are shown 4 pictures for each odor (10 odors in total), then they need to select what they sniffed. Have a 10-minute break. Part B: Participants sniff 20 different odors, 10 of which are the same odors as in Part A. They need to select the picture and figure out whether the odor is old or new. | From baseline to 18 months' follow-up and 36 months' follow-up |
| Longitudinal changes of odor-induced brain fMRI activation | Compare the change of odor-induced brain activation beta value from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up) | From baseline to 18 months' follow-up and 36 months' follow-up |
| Within 1 week after cognitive assessments |
| Longitudinal changes of brain structural MRI scan | Compare the change of cortical morphology from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up) | From baseline to 18 months' follow-up and 36 months' follow-up |
| Longitudinal changes of functional MRI scan | Compare the change of large-scale network functional connectivity from baseline to each follow-up time points (18 months' follow-up, 36 months' follow-up) | From baseline to 18 months' follow-up and 36 months' follow-up |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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