Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies

Zhang, Zhou; Zhang, Bing; Wang, Xin; Zhang, Xin; Yang, Qing; Qing, Zhao; Zhang, Wen; Zhu, Dalong; Bi, Yan

doi:10.2337/dc18-2584

Cited by 69 publications

(55 citation statements)

References 38 publications

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“…Olfactory tests were carried out using the Olfactory Function Assessment by Computerized Testing (OLFACT TM ) with a system from Osmic Enterprises (Cincinnati, OH, USA), as described previously. 16 The olfactory tests were computerized and standardized. The olfactory threshold test was conducted using a series of binary dilutions of an n-butanol solution in light mineral oil.…”

Section: Methodsmentioning

confidence: 99%

“… 15 The application of magnetic resonance imaging (MRI) and functional MRI (fMRI) have confirmed the reductions in odor-induced brain activation and the weakened functional connectivity (FC) in the olfactory network in patients with T2DM. 15 , 16 However, alterations in the olfactory network of patients with DPN have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Connecting Peripheral to Central Neuropathy: Examination of Nerve Conduction Combined with Olfactory Tests in Patients with Type 2 Diabetes

Zhang

et al. 2021

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Few studies have investigated the associations between diabetic peripheral neuropathy (DPN) and cognitive decline. Olfactory impairment is related to neurodegenerative diseases and type 2 diabetes mellitus (T2DM); however, the cognitive alterations of patients with DPN and the role of olfactory function in DPN are not known. We explored alterations in cognition with DPN and the associations of neuropathy parameters with cognition and olfaction. Methods: Healthy controls (HCs) and patients with T2DM underwent nerve-conduction tests, detailed cognitive assessment, olfactory-behavior tests, and odor-induced functional magnetic resonance imaging (fMRI). T2DM patients were divided into two groups (non-DPN [NDPN] and DPN). Olfactory brain regions showing different activation between the two groups were selected for functional connectivity (FC) analyses. A structural equation model (SEM) was also generated to demonstrate the association among cognition, olfactory, and neuropathy parameters. Results: One hundred individuals (36 HCs, 36 NDPN, and 28 DPN) were matched for age, sex, and educational level. Compared with the NDPN group, the DPN group had significantly lower scores for memory and processing speed, as well as lower olfactory identification and memory scores, decreased activation of the left frontal lobe, and reduced seed-based functional connectivity in the right insula. The nerve conduction velocity in patients with T2DM was associated with cognitive functions. The association between nerve conduction and executive function was mediated by olfactory behavior. Conclusion:Patients with DPN had worse cognition than the NDPN patients in the domains of memory and processing speed. Cognitive dysfunction could be predicted by olfactorybehavior tests and electrophysiological examination.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Connecting Peripheral to Central Neuropathy: Examination of Nerve Conduction Combined with Olfactory Tests in Patients with Type 2 Diabetes

Zhang

et al. 2021

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“…Similarly, higher sugar intake is related to increased striatal response to food cues and decreased GLP-1 release following glucose intake in lean human volunteers (Dorton et al, 2017). Changes in olfactory function have also been noted in obese individuals with type 2 diabetes -these changes are reversed following treatment with GLP-1R agonists (Zhang et al, 2019). This suggests circulating GLP-1 influences food preference in humans, potentially through interacting with neural reward systems as described in animal models.…”

Section: Glp-1mentioning

confidence: 95%

Gut peptide regulation of food intake – evidence for the modulation of hedonic feeding

Woodward

Gribble

Reimann

et al. 2021

The Journal of Physiology

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The number of people living with obesity has tripled worldwide since 1975 with serious implications for public health, as having obesity is linked to a significantly higher chance of early death from associated comorbidities (metabolic syndrome, type 2 diabetes and cardiovascular disease). As obesity is a consequence of food intake exceeding the demands of energy expenditure, efforts are made to better understand the homeostatic and hedonic mechanisms governing food intake. Gastrointestinal peptides are secreted from enteroendocrine cells in response to nutrient and energy intake, and modulate food intake either via afferent nerves, including the vagus nerve, or directly within the central nervous system, predominantly gaining access at circumventricular organs. Enteroendocrine hormones modulate homeostatic control centres at hypothalamic nuclei and the dorso-vagal complex. Additional roles of these peptides in modulating hedonic food intake and/or preference via the neural systems of reward are starting to be elucidated, with both peripheral and central peptide sources potentially contributing to central receptor activation. Pharmacological interventions and gastric bypass surgery for the treatment of type 2 diabetes and obesity elevate enteroendocrine hormone levels and also alter food preference. Hence, understanding of the hedonic mechanisms mediated by gut peptide action could advance development of potential therapeutic strategies for the treatment of obesity and its comorbidities. Key points-Enteroendocrine cells produce a range of gut peptides that have key roles in the regulation of appetite and beneficial effects on body weight. -Gut peptides are secreted as feedback to nutrient and energy intake, communicating directly or indirectly with the brain. -These peptides, some of which are also expressed in the CNS, alter food intake and reward via their widely distributed receptors. -Understanding these interactions is one of the challenges for developing effective pharmacotherapies that reduce feeding without producing negative side effects (e.g. nausea).

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“…Fifteen subjects (mean age: 27.20 ± 5.07 years, 11 females and 4 males) took part in the fMRI experiments. Their smell function was evaluated using the University of Pennsylvania Smell Identification Test (UPSIT) [43] and the OLFACT [44,45]. UPSIT tests an individual's ability to detect and identify suprathreshold odorants using 4 different 10-page booklets: 40 questions total.…”

Section: Participantsmentioning

confidence: 99%

“…Fifteen participants (mean age: 27.20 ± 5.07 years, 11 females and 4 males) took part in the fMRI and associated psychophysical experiments. Their smell function was evaluated using the University of Pennsylvania Smell Identification Test (UPSIT) [45] and the OLFACT [46,47].…”

Section: Participantsmentioning

confidence: 99%

Olfactory-Trigeminal Integration in the Primary Olfactory Cortex

Karunanayaka

Elyan

et al. 2020

Preprint

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Humans naturally integrate signals from the olfactory and intranasal trigeminal systems. A tight interplay has been demonstrated between these two systems, and yet the underlying neural circuitry that mediate olfactory-trigeminal integration remains unclear. Using functional magnetic resonance imaging (fMRI), this study investigated the neural mechanisms underlying olfactory-trigeminal integration. Fifteen subjects with normal olfactory function performed a localization task with weak or strong air-puff stimuli, phenylethyl alcohol (PEA; rose odor), or a combination. Although the ability to localize PEA to either nostril was at chance, its presence significantly improved the localization accuracy of weak, but not strong, air-puffs, relative to the localization of air-puffs without concomitant PEA, when both stimuli were delivered concurrently to the same nostril. This enhancement in localization accuracy was directly correlated with the magnitude of multisensory activity in the primary olfactory cortex (POC). Changes in orbitofrontal cortex (OFC) multisensory activity alone could not predict task performance, but changes in OFC and POC connectivity could. Similar activity and connectivity patterns were observed in the superior temporal cortex (STC), inferior parietal cortex (IPC) and the cerebellum.Taken together, these results suggest that olfactory-trigeminal integration is occurring across multiple brain regions. These findings can be interpreted as an indication that the POC is part of a distributed brain network that mediate the integration between olfactory and trigeminal systems.that multisensory effects in the OFC, STS and posterior parietal cortex (known higher-order multisensory brain regions) contribute to olfactory-trigeminal integration. Lastly, we tested the hypothesis that the effects of multisensory interaction in the POC is, in fact, driven by its connectivity with the OFC, STS and IPC.

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Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies

Cited by 69 publications

References 38 publications

Connecting Peripheral to Central Neuropathy: Examination of Nerve Conduction Combined with Olfactory Tests in Patients with Type 2 Diabetes

Connecting Peripheral to Central Neuropathy: Examination of Nerve Conduction Combined with Olfactory Tests in Patients with Type 2 Diabetes

Gut peptide regulation of food intake – evidence for the modulation of hedonic feeding

Olfactory-Trigeminal Integration in the Primary Olfactory Cortex

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