Insulin and cognitive function in humans: experimental data and therapeutic considerations

2005 ◽  
Vol 33 (5) ◽  
pp. 1037-1040 ◽  
Author(s):  
M.W.J. Strachan

Data from experimental studies in animals and from epidemiological studies in humans suggest a link between insulin and cognitive performance. Do these results translate into clinical and therapeutic benefit for people with cognitive impairment? Insulin injected peripherally can readily cross the blood–brain barrier. Intravenous insulin can improve aspects of cognitive function in healthy adults and in individuals with Alzheimer's dementia. Moreover, intravenous insulin increases concentrations of a long form of β-amyloid protein, Aβ42. One potential confounding factor with these data, however, is the need for co-administration of glucose with the insulin to maintain euglycaemia as glucose itself can facilitate memory function. Administration of insulin via the intranasal route is scientifically (and therapeutically) more attractive because the insulin goes directly to the cerebrospinal fluid, with minimal systemic absorption; this obviates the need for a glucose infusion. Intranasal insulin may improve some aspects of memory in healthy individuals, but has yet to be studied in people with cognitive impairment. TZDs (thiazolidinediones) reduce peripheral insulin concentrations by enhancing insulin sensitivity. In adults with Type II (non-insulin-dependent) diabetes, TZD therapy improves memory function, but so does sulphonylurea therapy (which elevates peripheral insulin concentrations). Improved memory is linked to lower blood glucose concentrations, rather than altered insulin levels. However, major trials are currently under way examining the impact of TZDs in people with dementia.

2018 ◽  
Vol 38 (12) ◽  
pp. 2112-2128 ◽  
Author(s):  
Monica M Santisteban ◽  
Costantino Iadecola

Dementia is growing at an alarming rate worldwide. Although Alzheimer disease is the leading cause, over 50% of individuals diagnosed with Alzheimer disease have vascular lesions at autopsy. There has been an increasing appreciation of the pathogenic role of vascular risk factors in cognitive impairment caused by neurodegeneration. Midlife hypertension is a leading risk factor for late-life dementia. Hypertension alters cerebrovascular structure, impairs the major factors regulating the cerebral microcirculation, and promotes Alzheimer pathology. Experimental studies have identified brain perivascular macrophages as the major free radical source mediating neurovascular dysfunction of hypertension. Recent evidence indicates that high dietary salt may also induce cognitive impairment. Contrary to previous belief, the effect is not necessarily associated with hypertension and is mediated by a deficit in endothelial nitric oxide. Collectively, the evidence suggests a remarkable cellular diversity of the impact of vascular risk factors on the cerebral vasculature and cognition. Whereas long-term longitudinal epidemiological studies are needed to resolve the temporal relationships between vascular risk factors and cognitive dysfunction, single-cell molecular studies of the vasculature in animal models will provide a fuller mechanistic understanding. This knowledge is critical for developing new preventive, diagnostic, and therapeutic approaches for these devastating diseases of the mind.


The prevalence of cognitive impairment caused by neurodegenerative diseases and other neurologic disorders associated with aging is expected to rise dramatically between now and year 2050, when the population of Americans aged 65 or older will nearly double. Cognitive impairment also commonly occurs in other neurologic conditions, as well as in non-neurologic medical disorders (and their treatments), idiopathic psychiatric illnesses, and adult neurodevelopmental disorders. Cognitive impairment can thus infiltrate all aspects of healthcare, making it necessary for clinicians and clinical researchers to have an integrated knowledge of the spectrum of adult cognitive disorders. The Oxford Handbook of Adult Cognitive Disorders is meant to serve as an up-to-date, scholarly, and comprehensive volume covering most diseases, conditions, and injuries resulting in impairments in cognitive function in adults. Topics covered include normal cognitive and brain aging, the impact of medical disorders (e.g., cardiovascular, liver, pulmonary) and psychiatric illnesses (e.g., depression and bipolar disorder) on cognitive function, adult neurodevelopmental disorders (e.g., Down Syndrome, Attention Deficit/Hyperactivity Disorder), as well as the various neurological conditions (e.g., Alzheimer’s disease, chronic traumatic encephalopathy, concussion). A section of the Handbook is also dedicated to unique perspectives and special considerations for the clinicians and clinical researchers, covering topics such as cognitive reserve, genetics, diversity, and neuroethics. The target audience of this Handbook includes: (1) clinicians, particularly psychologists, neuropsychologists, neurologists (including behavioral and cognitive neurologists), geriatricians, and psychiatrists (including neuropsychiatrists), who provide clinical care and management for adults with a diverse range of cognitive disorders; (2) clinical researchers who investigate cognitive outcomes and functioning in adult populations; and (3) graduate level students and post-doctoral trainees studying psychology, clinical neuroscience, and various medical specialties.


2018 ◽  
Vol 46 (3-4) ◽  
pp. 217-228 ◽  
Author(s):  
Mona Michelet ◽  
Knut Engedal ◽  
Geir Selbæk ◽  
Anne Lund ◽  
Guro Hanevold Bjørkløf ◽  
...  

Background/Aims: A timely diagnosis of dementia is important, and the Cognitive Function Instrument (CFI) is a newly developed instrument to screen for cognitive decline. The aim of this study was to evaluate the validity and internal consistency of the Norwegian version of the CFI. Methods: We included 265 participants with dementia, mild cognitive impairment (MCI), subjective cognitive impairment (SCI), and a reference group without subjective or assessed cognitive decline. The participants and their relatives answered the self- and proxy-rated versions of the CFI. Results: The Norwegian CFI had power to discriminate between people with dementia and with MCI, SCI, and the reference group. The proxy version had better power than the self-rated version in our participants (area under the curve [AUC] proxy-rated varying from 0.79 to 0.99, AUC self-rated varying from 0.56 to 0.85). Conclusion: The Norwegian CFI was found to be a useful, valid, and robust instrument.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kristin J Addison-Brown ◽  
Abraham J Letter ◽  
Henry K Yaggi ◽  
Leslie A McClure ◽  
Frederick W Unverzagt ◽  
...  

Introduction: Using a subsample from the national REasons for Geographic And Racial Differences in Stroke (REGARDS) study, we examined the associations of obstructive sleep apnea (OSA) with cognition and quality of life and whether these associations vary with age while controlling for other demographic factors and comorbid medical conditions. Methods: Stroke-free participants with complete data on OSA risk, cognition, and quality of life as of October 2010 were included (N =2,925; ages 47-93, 43% men, 35% black, 65% white). OSA risk was defined as high or low based on responses to the Berlin Sleep Questionnaire (BSQ). Cognitive function was assessed with three validated fluency and recall measures; quality of life was assessed with the 4-item Center for Epidemiological Studies-Depression (CESD-4) scale and the Medical Outcomes Study Short Form-12 (SF-12). MANCOVA statistics were applied to the cognitive and quality of life outcomes separately while accounting for potential confounders (age, sex, race, education, diabetes and dyslipidemia). Body mass index and hypertension were taken into account as part of the BSQ definition of OSA risk. Results: In fully adjusted models, those at high risk for OSA had significantly lower cognitive scores (p < .05) and lower quality of life (depressive symptoms and SF-12) (p < .0001) than those at low risk. Some of the associations were age-dependent, such that younger participants with high OSA risk had worse cognitive and quality of life scores than both younger participants with low OSA risk and older participants with high OSA risk. Discussion: Lower cognitive function and lower quality of life in those at high risk for sleep apnea remained after accounting for potentially confounding factors in a population-based sample. These relationships were more pronounced during middle age, with attenuated effects after age 70. It may be of particular importance to detect and treat OSA in younger adults.


Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1253 ◽  
Author(s):  
Sherman Bigornia ◽  
Tammy Scott ◽  
William Harris ◽  
Katherine Tucker

Polyunsaturated fatty acid (PUFA) consumption is recommended as part of a healthy diet, but evidence of the impact of individual species and biological concentrations on cognitive function is limited. We examined prospective associations of PUFA erythrocyte composition and dietary intake with measures of cognitive function among participants of the Boston Puerto Rican Health Study (aged 57 years). Erythrocyte and dietary PUFA composition were ascertained at baseline and associated with 2-year scores on the Mini-Mental State Exam (MMSE) (n = 1032) and cognitive domain patterns derived from a battery of tests (n = 865), as well as with incidence of cognitive impairment. Erythrocyte and dietary n-3 PUFA were not significantly associated with MMSE score. However, total erythrocyte and dietary n-3 very-long-chain fatty acids (VLCFA), and intake of individual species, were associated with better executive function (P-trend < 0.05, for all). There was evidence that greater erythrocyte n-6 eicosadienoic acid concentration was associated with lower MMSE and executive function scores (P-trend = 0.02). Only erythrocyte arachidonic acid (ARA) concentration predicted cognitive impairment (Odds Ratio = 1.26; P = 0.01). Among Puerto Rican adults, we found that n-3 VLCFA consumption may beneficially impact executive function. Further, these findings provide some evidence that n-6 metabolism favoring greater ARA tissue incorporation, but not necessarily dietary intake, could increase the risk of cognitive impairment.


2020 ◽  
pp. 1-28 ◽  
Author(s):  
Emily Shoesmith ◽  
Alys Wyn Griffiths ◽  
Cara Sass ◽  
Divine Charura

Abstract As there is currently no cure for dementia, providing psycho-social support is imperative. Counselling and psychotherapeutic interventions offer a way to provide individualised support for people with dementia and their families. However, to date, there has not been a systematic review examining the research evidence for these interventions. This review aimed to examine the following research questions: (1) Are counselling/psychotherapeutic interventions effective for people with dementia?, (2) Are counselling/psychotherapeutic interventions effective for care-givers of people with dementia? and (3) Which modes of delivery are most effective for people with dementia and care-givers of people with dementia? A systematic literature search was conducted in MEDLINE (via PubMed), PsycINFO and CINAHL in March 2019. Keyword searches were employed with the terms ‘dement*’, ‘counsel*’, ‘psychotherapy’, ‘therap*’, ‘care’ and ‘outcome’, for the years 2000–2019. Thirty-one papers were included in the review, from seven countries. Twenty studies were randomised controlled trials (RCTs) or adopted a quasi-experimental design. The remaining studies were qualitative or single-group repeated-measures design. The review identified variation in the counselling/psychotherapeutic approaches and mode of delivery. Most interventions adopted either a problem-solving or cognitive behavioural therapy approach. Mixed effectiveness was found on various outcomes. The importance of customised modifications for people with dementia was highlighted consistently. Understanding the dyadic relationships between people with dementia and their care-givers is essential to offering effective interventions and guidance for practitioners is needed. Information about the cognitive impairment experienced by participants with dementia was poorly reported and is essential in the development of this research area. Future studies should consider the impact of cognitive impairment in developing guidance for counselling/psychotherapeutic intervention delivery for people with dementia.


2016 ◽  
Vol 12 ◽  
pp. P234-P234
Author(s):  
Hiroko H. Dodge ◽  
Jian Zhu ◽  
Tiffany F. Hughes ◽  
Beth E. Snitz ◽  
Chung-Chou H. Chang ◽  
...  

2019 ◽  
Author(s):  
Michael Wenzel ◽  
Alexander Leunig ◽  
Shuting Han ◽  
Darcy S. Peterka ◽  
Rafael Yuste

SUMMARYProlonged medically-induced coma (pMIC), a procedure performed in millions of patients worldwide, leads to cognitive impairment, yet the underlying brain mechanism remains unknown. No experimental studies of medically-induced coma (MIC) exceeding ~6 hours exist. For MIC of less than 6 hours, studies in developing rodents have documented transient changes of cortical synapse formation. However, in adulthood, cortical synapses are thought to become stabilized. Here, we establish pMIC (up to 24 hrs) in adolescent and mature mice, and combine repeated behavioral object recognition assessments with longitudinal two-photon imaging of cortical synapses. We find that pMIC affects cognitive function, and is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the post-anesthetic period is dominated by synaptic loss. These results carry profound implications for intensive medical care, as they point out at significant structural side effects of pMIC on cortical brain synaptic architecture across age levels.


2020 ◽  
Author(s):  
Erica Dove ◽  
Rosalie Wang ◽  
Karl Zabjek ◽  
Arlene Astell

BACKGROUND While exercise can benefit the health and well-being of people with dementia or mild cognitive impairment, many exercise programs offered to this population are passive, unengaging, and inaccessible, resulting in poor adherence. Motion-based technologies are increasingly being explored to encourage exercise participation among people with dementia or mild cognitive impairment. However, the impacts of using motion-based technologies with people with dementia or mild cognitive impairment on variables including balance, movement confidence, and cognitive function have yet to be determined. OBJECTIVE The purpose of this study is to examine the impacts of a group motion-based technology intervention on balance, movement confidence, and cognitive function among people with dementia or mild cognitive impairment. METHODS In this quasi-experimental pre- and posttest design, we will recruit 24 people with dementia or mild cognitive impairment from 4 adult day programs and invite them to play Xbox Kinect bowling in a group setting, twice weekly for 10 weeks. We will require participants to speak and understand English, be without visual impairment, and be able to stand and walk. At pretest, participants will complete the Mini-Balance Evaluation Systems Test (Mini-BESTest) and the Montreal Cognitive Assessment (MoCA). We will video record participants during weeks 1, 5, and 10 of the intervention to capture behavioral indicators of movement confidence (eg, fluency of motion) through coding. At posttest, the Mini-BESTest and MoCA will be repeated. We will analyze quantitative data collected through the Mini-BESTest and the MoCA using an intent-to-treat analysis, with study site and number of intervention sessions attended as covariates. To analyze the videos, we will extract count and percentage data from the coded recordings. RESULTS This study will address the question of whether a group motion-based technology intervention, delivered in an adult day program context, has the potential to impact balance, movement confidence, and cognitive function among people with dementia or mild cognitive impairment. The project was funded in 2019 and enrollment was completed on February 28, 2020. Data analysis is underway and the first results are expected to be submitted for publication in 2021. CONCLUSIONS This study will assess the feasibility and potential benefits of using motion-based technology to deliver exercise interventions to people with dementia or mild cognitive impairment. This work can also be used as the basis for developing specific software and future exercise programs using motion-based technology for people with dementia or mild cognitive impairment, as well as understanding some of the conditions in which these programs can be delivered. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/18209


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