High Hemoglobin A1c and Diabetes Predict Memory Decline in the Health and Retirement Study

Marden, Jessica R.; Mayeda, Elizabeth Rose; Tchetgen, Eric J. Tchetgen; Kawachi, Ichiro; Glymour, M. Maria

doi:10.1097/wad.0000000000000182

Cited by 39 publications

(34 citation statements)

References 39 publications

(59 reference statements)

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Section: Possible Mechanism Underlying the Connectionsupporting

confidence: 53%

“…High levels of HbA1c were found to be associated with high white matter hyperintensity, which suggest a possible role of HbA1c behind the decline in memory in elderly patients with diabetes (Tamura et al, 2017). This was further supported by the data which revealed memory decline when the HbA1c levels were higher than normal (Marden, Mayeda, Tchetgen, Kawachi, & Glymour, 2017 Apart from the role of insulin, HbA1c and GSK-3β, several metabolic changes like disturbed alanine, lactate, glutamine, glutamate, and glycine levels were suggested as a link to cognitive dysfunction in diabetic mice brain (Zheng et al, 2017). Also, islet amyloid polypeptide (IAPP) was found to interact with Aβ and accelerate its pathology.…”

Section: Possible Mechanism Underlying the Connectionmentioning

confidence: 52%

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Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease

Jash

Gondaliya

Kirave

et al. 2019

Drug Development Research

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Diabetes mellitus (DM) is a gradually rising metabolic disease which is currently affecting millions of people worldwide. Diabetes is associated with various complications like nephropathy, neuropathy, retinopathy, diabetic foot, cognitive impairment, and many more. Evidence suggests that cognitive dysfunction is a rising complication of diabetes which adversely affects the brain of patients suffering from diabetes. Age‐related memory impairment is a complication having its major effect on people suffering from diabetes and Alzheimer's. Patients suffering from diabetes are at two times higher risk of developing cognitive dysfunction as compared with normal individuals. Multiple factors which are involved in diabetes related complications are found to play a role in the development of neurodegeneration in Alzheimer's. The problem of insulin deficiency and insulin resistance is well reported in diabetes but there are many studies which suggest dysregulation of insulin levels as a reason behind the development of Alzheimer's. As the link between diabetes and Alzheimer disease (AD) is deepening, there is a need to understand the plausible tie‐ins between the two. Emerging role of major factors like insulin imbalance, advanced glycation end products and micro‐RNA's involved in diabetes and Alzheimer's have been discussed here. This review helps in understanding the plausible mechanism underlying the pathophysiology of amyloid beta (Aβ) plaque formation and tau hyperphosphorylation as well provides information about studies carried out in this area of research. The final thought is to enhance the scientific knowledge on this correlation and develop future therapeutics to treat the same.

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Section: Possible Mechanism Underlying the Connectionsupporting

confidence: 53%

Section: Possible Mechanism Underlying the Connectionmentioning

confidence: 52%

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease

Jash

Gondaliya

Kirave

et al. 2019

Drug Development Research

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“…In the Framingham Heart Study, fasting plasma glucose (FPG) was strongly associated with abnormalities of the cerebral microstructure and cognition, particularly in memory and attention domains, with consistent results even in young adults . Rolandsson et al observed a negative association between fasting and 2‐hour plasma glucose and episodic memory in women without type 2 diabetes, but not in men , and in the Health and Retirement Study, increased glycated hemoglobin (HbA1c) levels were associated with longitudinal memory decline . Impaired insulin sensitivity measured using the homeostatic model assessment (HOMA) index also was associated with cognitive dysfunction .…”

Section: Introductionmentioning

confidence: 95%

Glycated Hemoglobin, but not Insulin Sensitivity, is Associated with Memory in Subjects with Obesity

Arnoriaga-Rodríguez

Blasco

Coll

et al. 2019

Obesity

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Objective: Obesity has been related to later-life dementia. Serum glucose levels and insulin resistance are known to influence cognition in individuals with diabetes. This study aimed to evaluate memory function in middle-aged individuals with obesity in association with glucose metabolism and brain iron content. Methods: This was a cross-sectional case-control study including 121 participants aged 27.2 to 66.6 years (56 without obesity, 65 with obesity) stratified according to sex and menopausal status. Insulin sensitivity, body composition, brain iron content, and memory function were evaluated by euglycemic hyperinsulinemic clamp, dual-energy x-ray absorptiometry, magnetic resonance relaxometry (R2*), and California Verbal Learning Test, respectively. Results: Women with obesity, but not men, had lower scores in some California Verbal Learning Tests in association with metabolic parameters and increased brain iron content compared with controls. Fasting plasma glucose, glycated hemoglobin (HbA1c; within normal range), and R2* were negatively associated with memory scores, whereas insulin sensitivity showed positive associations. Remarkably, only HbA1c levels and R2* in the right inferior fronto-orbital region remained significant after controlling for age, sex, education, and BMI. Conclusions: Impairments in memory function in middle-aged women with obesity are associated with HbA1c levels and brain iron content independently of insulin sensitivity. These results may have implications in the design of therapeutic strategies in women with obesity.Obesity (2019) 27, 932-942.

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“…They go well along with the longitudinal data of the large U.S. Health and Retirement Study [16]. The strength of the effect of hyperglycemia may be deduced from the fact that the significant relationships of HbA1c to cognitive performance could be even found in a cross-sectional examination of a moderately large non-representative sample of memory clinic patients.…”

Section: Resultsmentioning

confidence: 69%

Glycilated Hemoglobin and Cognitive Impairment

Binder¹,

Marczak²,

Adler³

2017

Int J Neurol Neurother

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Objective: Hyperglycemia and type 2 diabetes mellitus have been shown to have a negative impact on cognitive performance in older adults. In order to assess the relevance of this effect in memory clinic patients, we examined the relationship between hyperglycemia and cognition in an unselected out-patient sample. Design:In a cross-sectional study in memory clinic patients, glycosylated hemoglobin (HbA1c) was determined and related to cognitive performance, subjective memory impairment, and self-perceived cognitive blackouts. Results:The frequency of mild cognitive impairment or mild dementia of the Alzheimer type was increased 1.7-fold in subjects with hyperglycemia. The HbA1c value was negatively correlated with global cognitive performance as well as with orientation, short-term memory and visuospatial capabilities. The frequency of cognitive blackouts was positively correlated with HbA1c levels and it was increased in hyperglycemic subjects.Conclusions: Hyperglycemia could be confirmed as a major risk factor for cognitive impairment. This could be shown even in a non-representative cross-sectional memory clinic sample. Thus, the HbA1c determination may be recommended for a routine diagnostic memory clinic work-up. KeywordsDiabetes mellitus, Hyperglycemia, HbA1c, Mild cognitive impairment, Dementia, Alzheimer, Subjective memory impairment, Cognitive blackouts, Memory clinic [7]. Even prediabetes and insulin resistance are associated with cognitive decline and brain atrophy [8].Diabetes may compromise cognitive function by various mechanisms, such as brain vascular lesions, insulin resistance, oxidative stress, the accumulation of advanced glycilation end products, inflammation or a competition of insulin and β-amyloid on the insulin-degrading enzyme [9].This may also apply to subjects with prediabetes as reflected by a moderately increased HbA1c level. Accordingly, it has been shown that the HbA1c value correlates with the rate of brain atrophy [10] and that it predicts conversion to dementia and mild cognitive impairment [11]. Glycosilated hemoglobin (HbA1c) is a measure of blood glucose concentration over the past two to three months and is used both for the diagnosis of diabetes and the assessment of diabetes management [12].We studied the effects of diabetes and hyperglycemia as determined by elevated HbA1c values on cognitive performance, subjective memory impairment and self-perceived cognitive blackouts in a group of patients of our memory clinic. Subjects and MethodsThe analyses were carried out in 113 patients consecutively presenting for the first time for memory assessment at our memory clinic. They were 70 women (61.9%) and 43 men (38.1%) at ages between 50 and 87 years (mean ± SD: 61.2 ± 9.1 years). Subjects with a history of neurological disorder, with an actual neurological or psychiatric disorder, or with a medication that may compromise cognitive performance were not

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High Hemoglobin A1c and Diabetes Predict Memory Decline in the Health and Retirement Study

Cited by 39 publications

References 39 publications

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease

Glycated Hemoglobin, but not Insulin Sensitivity, is Associated with Memory in Subjects with Obesity

Glycilated Hemoglobin and Cognitive Impairment

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