Diabetes in Midlife and Cognitive Change Over 20 Years

Rawlings, Andreea M.; Sharrett, A. Richey; Schneider, Andrea L.C.; Coresh, Josef; Albert, Marilyn; Couper, David J.; Griswold, Michael; Gottesman, Rebecca F.; Wagenknecht, Lynne E.; Windham, B. Gwen; Selvin, Elizabeth

doi:10.7326/m14-0737

Cited by 367 publications

(316 citation statements)

References 34 publications

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“…1,[6][7][8][9] In a 9-year longitudinal study of 824 Catholic nuns, priests, and brothers, those with T2D showed, for instance, ∼1.6-fold increased risk of developing AD. 10 The Atherosclerosis Risk in Communities study, 11 the Whitehall II study, 12 and other studies have confirmed such an association, as reviewed by Cukierman et al 13 Pathologic features of AD include deposit of extracellular amyloid plaques that consist of aggregated amyloid b-protein (Ab) and formation of soluble Ab oligomers. Ab originates from the proteolysis of the Amyloid Precursor Protein (APP) 14 by the sequential enzymatic actions of b-site APP-cleaving enzyme 1 and g-secretase.…”

Section: What's Known On This Subjectmentioning

confidence: 93%

Biomarkers of Alzheimer Disease, Insulin Resistance, and Obesity in Childhood

Luciano¹,

Barraco²,

Muraca³

et al. 2015

PEDIATRICS

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OBJECTIVE: To answer the question of whether onset of insulin resistance (IR) early in life enhances the risk of developing dementia and Alzheimer disease (AD), serum levels of 2 molecules that are likely associated with development of AD, the amyloid b-protein 42 (Ab42) and presenilin 1 (PSEN1), were estimated in 101 preschoolers and 309 adolescents of various BMI.METHODS: Participants (215 boys; 48.8%) were normal weight (n = 176; 40%), overweight (n = 135; 30.7%), and obese (n = 129; 29.3%). The HOmeostasis Model of IR (HOMA-IR), HOMA percent b-cell function (HOMA-b) and QUantitative Insulin-sensitivity Check Index (QUICKI) were calculated. RESULTS:Obese adolescents had values of Ab42 higher than overweight and normal-weight peers (190.2 6 9.16 vs 125.9 6 7.38 vs 129.5 6 7.65 pg/mL; P , .0001) as well as higher levels of PSEN1 (2.34 6 0.20 vs 1.95 6 0.20 vs 1.65 6 0.26 ng/mL; P , .0001). Concentrations of Ab42 were significantly correlated with BMI (r = 0.262; P , .0001), HOMA-IR (r = 0.261; P , .0001) and QUICKI (r = 20.220; P , .0001). PSEN1 levels were correlated with BMI (r = 0.248; P , .0001), HOMA-IR (r = 0.242; P , .0001), and QUICKI (r = 20.256; P , .0001). Western blot analysis confirmed that PSEN1 assays measured the full-length protein.CONCLUSION: Obese adolescents with IR present higher levels of circulating molecules that might be associated with increased risk of developing later in elderly cognitive impairment, dementia, and AD. WHAT'S KNOWN ON THIS SUBJECT:Insulin resistance plays a role in obesity. Recently it has been associated with increased risk of AD. Ab42 and PSEN1 are molecules associated with increased risk of later AD. Patients affected by AD show elevated levels of plasma Ab42.WHAT THIS STUDY ADDS: Levels of Ab42 and PSEN1 are significantly elevated in obese adolescents and correlated with the degree of both adiposity and systemic insulin resistance. Dr Manco conceptualized and designed the study, performed assays, analyzed data and interpreted results, contributed to the discussion, and critically revised the manuscript; Ms Luciano and Ms Barraco conceptualized and designed the study, performed assays, analyzed data and interpreted results, and drafted the manuscript; Drs Muraca, Ottino, Sforza, Rustico, and Morino and Ms Spreghini enrolled patients, collected growth data, and revised the manuscript for important intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. This condition has been termed as "brain insulin resistance" and seems to be a constant trait that precedes clinical symptoms of dementia and AD even for decades. Researchers refer to AD also as "type 3 diabetes" by virtue of the analogous brain glucose hypometabolism that characterizes both conditions and the high rate of their co-occurrence. 1,4,5 Patients with T2D exhibit an increased risk of developing cognitive impairment and dementia and, vice versa, impaired fasting glucose and diabetes are highly prevalent among patients...

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Section: What's Known On This Subjectmentioning

confidence: 93%

Biomarkers of Alzheimer Disease, Insulin Resistance, and Obesity in Childhood

Luciano¹,

Barraco²,

Muraca³

et al. 2015

PEDIATRICS

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“…To control the effect of age and education on scores, the subjects were stratified into the three age groups (34-44-45-64 and 65+ years) and the four levels of education (<8, 8-10, 11-14 and 14+ years of schooling) we used in this study. Lowered global cognitive function is defined as one or more standard deviation below average in each age and education strata [4,28]. Besides, as our study aims to perform multiple cognitive tests over time, we will be able to investigate the direction and magnitude of the influence of education on aging cognitive decline of this cohort of workers from a developing country.…”

Section: Discussionmentioning

confidence: 99%

“…Even though functional impairment is required for a diagnosis of dementia, longitudinal analyses of an agerelated cognitive decline rely mainly upon psychometrics procedures that are strongly dependent on educational background [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Education Plays a Greater Role than Age in Cognitive Test Performance among Participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Passos

Giatti

Chor

et al. 2015

International Journal of Epidemiology

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Background: Brazil has gone through fast demographic, epidemiologic and nutritional transitions and, despite recent improvements in wealth distribution, continues to present a high level of social and economic inequality. The ELSA-Brasil, a cohort study, aimed at investigating cardiovascular diseases and diabetes, offers a great opportunity to assess cognitive decline in this aging population through time-sequential analyses drawn from the same battery of tests over time. The purpose of this study is to analyze the influence of sex, age and education on cognitive tests performance of the participants at baseline. Methods: Analyses pertain to 14,594 participants with aged 35 to 74 years, who were functionally independent and had no history of stroke or use of neuroleptics, anticonvulsants, cholinesterase inhibitors or antiparkinsonian agents. Mean age was 52.0 ± 9.0 years and 54.2 % of participants were women. Cognitive tests included the word memory tests (retention, recall and recognition), verbal fluency tests (VFT, animals and letter F) and Trail Making Test B. Multivariable linear regression analysis was used to determine the influence of sociodemographic characteristics on the distribution of the final score of each test. Results: Women had significant and slightly higher scores than men in all memory tests and VFT, but took more time to perform Trail B. Reduced performance in all tests was seen with an increase age and, more importantly, with decrease level of education. The word list and VFT scores decreased at about one word for every 10 years of age; whereas higher-educated participants scored four words more on the word list test, and six or seven more correct words on VFT, when compared to lower-educated participants. Additionally, the oldest and less educated participants showed significant lower response rates in all tests. Conclusions: The higher influence of education than age in this Brazilian population reinforce the need for caution in analyzing and diagnosing cognitive impairments based on traditional cognitive tests and the importance of searching for education-free cognitive tests, especially in low and middle-income countries.

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“…A meta-analysis of longitudinal studies reported that individuals with diabetes had 1.21-fold significantly increased odds of having Alzheimer's disease, 1.51-fold higher risk for any dementia and 1.21 higher risk for mild cognitive impairment compared to non-diabetic individuals [3]. Another large study revealed that diabetes in midlife was associated with a 19% greater cognitive decline over 20 year period [4]. Aging itself has also an independent impact on greater risk of cognitive decline.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin Levels in Elderly, Diabetic Patients with Mild Cognitive Impairment

Górska-Ciebiada¹,

Cypryk²,

Borkowska³

et al. 2018

Neuropsychiatry

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Objective:The etiology of cognitive impairment in diabetes is unknown, but probably associated with many factors. One of the recent hypotheses suggests that ghrelin could be involved in cognitive impairment in diabetic patients. It has been reported that ghrelin signaling occurs in the hippocampus and improves memory and spatial learning. The aim of this study was to evaluate serum levels of ghrelin in elderly, diabetic patients with and without mild cognitive impairment (MCI) and to determine the predictors of having MCI in elderly diabetics. Methods:The cross-sectional study was conduct among 276 elderly subjects with type 2 diabetes. 87 patients with MCI and 189 controls were selected according to the criteria proposed by the MCI Working Group of the European Consortium on Alzheimer's Disease (using the Montreal Cognitive Assessment: MoCA score). Data of biochemical parameters and biomarkers were collected. The serum levels of ghrelin were assessed using ELISA kit. Results:Serum levels of ghrelin were significantly lower in patients with MCI compared to controls. In MCI patients serum ghrelin levels were positively correlated with MoCA score and negatively correlated with HbA1c and BMI. The logistic regression models revealed that variables which increased the likelihood of diagnosis of MCI in elderly diabetic patients were: lower levels of ghrelin, higher levels of HbA1c, hypertension, previous cardiovascular disease, increased number of co-morbidities, and less years of formal education. Conclusion:In summary, serum levels of ghrelin were decreased in MCI elderly diabetic patients compared to controls and associated with poor MoCA score. The results indicated that lower ghrelin levels may be a risk factor for a cognitive impairment in diabetic, elderly patients. Further prospective larger studies are needed to confirm the role of this marker in the progression to dementia.

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Diabetes in Midlife and Cognitive Change Over 20 Years

Cited by 367 publications

References 34 publications

Biomarkers of Alzheimer Disease, Insulin Resistance, and Obesity in Childhood

Biomarkers of Alzheimer Disease, Insulin Resistance, and Obesity in Childhood

Education Plays a Greater Role than Age in Cognitive Test Performance among Participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Ghrelin Levels in Elderly, Diabetic Patients with Mild Cognitive Impairment

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