Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes

Novak, Vera; Milberg, William; Hao, Ying; Munshi, Medha N.; Novák, Péter; Galica, Andrew; Manor, Bradley; Roberson, Paula K.; Craft, Suzanne; Abduljalil, Amir M.

doi:10.2337/dc13-1672

Cited by 175 publications

(166 citation statements)

References 37 publications

(56 reference statements)

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“…A study of a middle-aged population showed that the management of prediabetes and diabetes with tight glycemic control during the midlife may protect against cognitive decline in late life (3). These results are encouraging and strengthen recommendations for tighter glycemic control in middle-aged populations with diabetes (29). On the other hand, there is clear evidence that the intensive control of blood glucose, blood pressure, or cholesterol levels in the older population is not beneficial in preventing cognitive decline (25,41).…”

Section: How Should a Clinician Approach The Care Of An Older Patientmentioning

confidence: 64%

“…Small studies have also evaluated the impact of glucose excursions on cognitive function and found an association between the diurnal variation and postprandial elevation of glucose levels with a cognitive decline (27,28). Some preliminary data suggest short-term improvement of cognitive function in patients with type 2 diabetes treated with intranasal insulin via the impact on anterior brain vasodilatation (29). Further research is needed to understand this area more clearly so that a targeted approach can be developed for the older adults at risk for cognitive dysfunction.…”

Section: Hyperglycemiamentioning

confidence: 99%

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Cognitive Dysfunction in Older Adults With Diabetes: What a Clinician Needs to Know

2017

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One of the challenges of managing older adults with diabetes is the individualization of care in people with multiple comorbid conditions. Although macrovascular and microvascular complications of diabetes are well recognized, there is a lack of awareness regarding other conditions such as cognitive dysfunction, depression, and physical disabilities. Cognitive dysfunction is of particular importance because of its impact on self-care and quality of life. In this Perspective, I discuss common and practical questions faced by clinicians managing diabetes in older adults who also have cognitive dysfunction.

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Section: How Should a Clinician Approach The Care Of An Older Patientmentioning

confidence: 64%

Section: Hyperglycemiamentioning

confidence: 99%

Cognitive Dysfunction in Older Adults With Diabetes: What a Clinician Needs to Know

2017

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“…Currently, no other hippocampal perfusion studies are available in participants with type 2 diabetes, and global (whole brain) perfusion studies show inconclusive results (20,21). Moreover, insulin administration in participants with type 2 diabetes leads to reduced cerebral perfusion in the insular cortex and improved cognitive performance (22).…”

Section: Microvasculaturementioning

confidence: 99%

On the Interplay of Microvasculature, Parenchyma, and Memory in Type 2 Diabetes

et al. 2015

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OBJECTIVEType 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODSThirty-nine participants with type 2 diabetes (64.5 6 6.1 years old) and 34 participants without type 2 diabetes (58.3 6 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTSFor the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONSIn addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.Type 2 diabetes is associated with cognitive deficits, accelerated cognitive decline, and an increased risk of dementia and Alzheimer disease (AD) (1-3). A prominently affected cognitive domain in type 2 diabetes is memory (4), for which the hippocampus plays an essential role. In patients with type 2 diabetes and memory problems, reduced hippocampal volumes have previously been reported (5). Furthermore, chronic hyperglycemia has been shown to be associated with altered hippocampal microstructure and memory performance in elderly individuals without diabetes (6). Unfortunately, the exact mechanism underlying hyperglycemia and

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“…Two recent proof-of-concept studies evaluated the acute effects on cerebral vasoreactivity and cognition of a single 40 IU dose of intranasal insulin (Novolin®) via a ViaNase™ device compared with placebo in type 2 Diabetes (T2DM; [64,65]). Across all subjects, intranasal insulin administered improved visuospatial memory and increased resting-state functional connectivity in older adults with T2DM.…”

Section: Is N2b Insulin Appropriate As Therapy For Neurodegenerative mentioning

confidence: 99%

Nose-to-Brain delivery of insulin for Alzheimer’s disease

Stützle¹,

Flamm²,

Carle

et al. 2015

ADMET DMPK

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The transport of small molecules, peptides and proteins via the olfactory epithelium and along olfactory and trigeminal nerve pathways from the nasal cavity to the brain is very well known and clinically established for central nervous system (CNS) active drugs like oxytocin, sumatriptan or insulin. Insulin is a clinically well-established biopharmaceutical with a validated function in cognition. Central supply with insulin via intranasal administration improves cognition in animal models CNS delivery -an unmet medical needThe World Health Organization (WHO) estimates that more than a billion people worldwide are suffering from diseases of the central nervous system (CNS; [1,2]). Alzheimer's disease (AD) is the most common neurodegenerative dementia in the industrialized world, with prevalence rates well over 30 % in the over 80-years-old population [1,2]. AD causes enormous costs to the social healthcare systems, as well as personal tragedies for the patients, families and caregivers. Like most neurodegenerative diseases, AD has a poor prognosis and only symptomatic therapy is currently available. Efficient treatment strategies are still limited and an aging society in demographic change presents an enormous challenge to the health systems of industrialized nations. Despite the extensive research and effort to uncover the mechanism of AD pathogenesis, more or less all drug candidates failed to demonstrate significant effects on cognition in clinical trials [3,4].A highly critical point in that context is the low central availability of drugs. The passage of most CNSactive drugs and in particular of biopharmaceuticals is massively hampered by the blood-brain barrier

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Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes

Cited by 175 publications

References 37 publications

Cognitive Dysfunction in Older Adults With Diabetes: What a Clinician Needs to Know

Cognitive Dysfunction in Older Adults With Diabetes: What a Clinician Needs to Know

On the Interplay of Microvasculature, Parenchyma, and Memory in Type 2 Diabetes

Nose-to-Brain delivery of insulin for Alzheimer’s disease

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