Associations of hemoglobin A1c with cognition reduced for long diabetes duration

IntroductionAssociations of some risk factors with poor cognition, identified prior to age 75, are reduced or reversed in very old age. The Protected Survivor Model predicts this interaction due to enhanced survival of those with extended risk factor duration. In a younger sample, this study examines the association of cognition with the mean hemoglobin A1c risk factor over the time at risk, according to its duration.MethodsThe interaction of mean hemoglobin A1c (averageâ =â 9.8%), evaluated over duration (averageâ =â 116.8â months), was examined for overall cognition and three cognitive domains in a sample of 150 â youngâ oldâ veterans (mean ageâ =â 70) with type 2 diabetes.ResultsThe predicted interactions were significant for overall cognition and attention, but not executive functions/language and memory.DiscussionFindings extend the Protected Survivor Model to a â youngâ oldâ sample, from the very old. This model suggests focusing on individuals with good cognition despite prolonged high risk when seeking protective factors.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152553/1/trc2jtrci201911009.pd

Depressive Symptoms Are Associated with Cognitive Function in the Elderly with Type 2 Diabetes

Background: Type 2 diabetes (T2D) is a metabolic condition associated with poor clinical and cognitive outcomes including vascular disease, depressive symptoms, cognitive impairment, and dementia. In the general elderly population, depression has been consistently identified as a risk factor for cognitive impairment/decline. However, the association between depression and cognitive function in T2D has been understudied. Objective: We investigated the association between depression and cognitive function in a large sample of cognitively normal elderly with T2D. Methods: In this cross-sectional study, we examined 738 participants, aged 65–88 years old, enrolled in the Israel Diabetes and Cognitive Decline study. For each cognitive domain (Episodic Memory, Executive Function, Attention/Working Mem- ory, Language/Semantic Categorization) and Overall Cognition, multiple linear regressions assessed its association with depression (score greater than 5 on the 15-item version of the Geriatric Depression Scale [GDS]), adjusting for age, sex, and education. Results: Depression (n = 66, 8.9%) was associated with worse performance on tasks of Executive Function (p = 0.004), Language/Semantic Categorization (p \u3c 0.001), and Overall Cognition (p \u3c 0.002), but not Episodic Memory (p = 0.643) or Attention/Working Memory (p = 0.488). Secondary analyses using GDS as a continuous variable did not sub- stantially change the results. Adjusting also for a history of antidepressant medication use slightly weakened the findings. Conclusion: Significant associations of depression with several cognitive domains and Overall Cognition even in cognitively normal elderly with T2D, suggest that depression may have a role in impaired cognitive function in T2D, which may be attenuated by antidepressants

Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes: Findings From the Action to Control Cardiovascular Risk in Diabetes–Memory in Diabetes (ACCORD-MIND) Study

IMPORTANCE African American individuals have higher dementia risk than individuals of white race/ethnicity. They also have higher rates of type 2 diabetes, which may contribute to this elevated risk. This study examined the association of the following 2 classes of alleles at the haptoglobin (Hp) locus that are associated with poor cognition, cardiovascular disease, and mortality: Hp 1-1 (associated with poor cognition and cerebrovascular disease) and Hp 2-1 and Hp 2-2 (associated with greater risk ofmyocardial infarction and mortality). An additional polymorphism in the promoter region of the Hp 2 allele, restricted to individuals of African descent, yields a fourth genotype, Hp 2-1m. African American adults have a higher prevalence of Hp 1-1 (approximately 30%) compared with individuals of white race/ethnicity (approximately 14%), but the potential role of the Hp genotype in cognition among elderly African American individuals with type 2 diabetes is unknown. OBJECTIVE To assess the association of the Hp genotypes with cognitive function and decline in elderly African American adults with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS This cohort study used publicly available data and specimens from the Action to Control Cardiovascular Risk in Diabetes–Memory in Diabetes (ACCORD-MIND) study to investigate the association of the Hp genotypes with cognitive function and decline in 466 elderly African American participants with type 2 diabetes. The hypothesis was that the Hp 1-1 genotype compared with the other genotypes would be associated with more cognitive impairment and faster cognitive decline in elderly African American adults with type 2 diabetes. The initial ACCORD trialwas performed from October 28, 1999, to September 15, 2014. This was a multicenter clinical study performed in an academic setting. EXPOSURES The Hp genotypes were determined from serum samples by polyacrylamide gel electrophoresis and by enzyme-linked immunosorbent assay. MAIN OUTCOMES AND MEASURES The Mini-Mental State Examination (MMSE) was used to measure cognitive function and change after 40 months. The MMSE score ranges from 0 to 30 points; higher scores represent better cognition. Associations were examined with analysis of covariance and linear regression, adjusting for age, sex, education, baseline glycated hemoglobin level, systolic blood pressure, diastolic blood pressure, cholesterol level, creatinine level, and treatment arm (intensive vs standard). The cognitive change model adjusted also for the baseline MMSE score. RESULTS Among 466 African American study participants (mean [SD] age, 62.3 [5.7] years), 64.8% were women, and the genotype prevalences were 29.4%(n = 137) for Hp 1-1, 36.1%(n = 168) for Hp 2-1, 10.9%(n = 51) for Hp 2-1m, and 23.6%(n = 110) for Hp 2-2. The groups differed in their baseline MMSE scores (P = .006): Hp 1-1 had the lowest MMSE score (mean [SE], 25.68 [0.23]), and Hp 2-1m had the highest MMSE score (mean [SE], 27.15 [0.36]). Using the least squares method, the 40-month decline was significant for Hp 1-1 (mean [SE], −0.41 [0.19]; P = .04) and for Hp 2-2 (mean [SE], −0.68 [0.21]; P = .001). However, the overall comparison across the 4 groups did not reach statistical significance for the fully adjusted model. The interaction of age with the Hp 1-1 genotype on MMSE score decline estimate per year change was significant (mean [SE], −0.87 [0.37]; P = .005), whereas itwas not significant for Hp 2-1 (mean [SE], 0.06 [0.37]; P = .85), Hp 2-1m (mean [SE], −0.06 [0.51]; P = .89), and Hp 2-2 (mean [SE], −0.44 [0.41]; P = .29), indicating that cognitive decline in Hp 1-1 carrierswas accentuated in older ages, whereas it was not significant for the other Hp genotypes. CONCLUSIONS AND RELEVANCE In this study, the Hp 1-1 genotype, which is 2-fold (approximately 30%) more prevalent among African American individuals than among individuals of white race/ ethnicity, was associated with poorer cognitive function and greater cognitive decline than the other Hp genotypes. The Hp gene polymorphism may explain the elevated dementia risk in African American adults. The neuropathological substrates and mechanisms for these associations merit further investigation

The Association of Depressive Symptoms With Brain Volume Is Stronger Among Diabetic Elderly Carriers of the Haptoglobin 1-1 Genotype Compared to Non-carriers

Aim: Depression is highly prevalent in type 2 diabetes and is associated with lower adherence to medical treatments, worse glycemic control, and increased risk for diabetes-related complications. The mechanisms underlying depression in type 2 diabetes are unclear. The haptoglobin (Hp) genotype is associated with type 2 diabetes related complications including increased risk for cerebrovascular pathology and worse cognitive performance. Its relationship with depression is unknown. We investigated the role of Hp genotype on the association of depression with brain and white matter hyperintensities (WMH) volumes.Methods: Depressive symptoms (measured with the 15-item Geriatric Depression Scale), brain MRI, and Hp genotypes, were examined in elderly subjects with type 2 diabetes [29 (13.8%) Hp 1–1 carriers and 181 (86.2%) non-carriers]. The interaction of Hp genotype with number of depressive symptoms on regional brain measures was assessed using regression analyses.Results: The significant interactions were such that in Hp 1–1 carriers but not in non-carriers, number of depressive symptoms was associated with overall frontal cortex (p = 0.01) and WMH (p = 0.04) volumes but not with middle temporal gyrus volume (p = 0.43).Conclusions: These results suggest that subjects with type 2 diabetes carrying the Hp 1–1 genotype may have higher susceptibility to depression in the context of white matter damage and frontal lobe atrophy. The mechanisms underlying depression in diabetes may differ by Hp genotype

Decreased Motor Function Is Associated with Poorer Cognitive Function in Elderly with Type 2 Diabetes

Background/Aims: Impaired motor function has been associated with cognitive impairment and dementia, but this relationship is poorly understood in elderly with type 2 diabetes (T2D). We thus investigated it in a large sample (n = 726) of cognitively normal elderly with T2D. Methods: In this cross-sectional study, hierarchical linear regressions assessed correlations of 3 motor measures (timed walk, grip strength, and self-reported motor difficulties) with episodic memory, attention/working memory, semantic categorization, executive function, and overall cognition controlling for demographics. Results: Longer timed walk and weaker grip strength were associated with poorer performance in all cognitive domains except episodic memory. Conclusions: Associations of motor and cognitive functions in T2D and non-T2D samples are consistent. A lack of association of motor function with episodic memory may suggest non-Alzheimer's disease-related underlying mechanisms

Neuropsychological Test Performance in Cognitively Normal Spanish-speaking Nonagenarians with Little Education

To find associations of age, sex, and education with neuropsychological test performance in cognitively normal Spanish-speaking Costa Rican nonagenarians with little education; to provide norms; and to compare their performance with similar Puerto Ricans. For 95 Costa Ricans (90–102 years old, 0–6 years of education), multiple regression assessed associations with demographics of performance on six neuropsychological tests. Analyses of covariance compared them with 23 Puerto Ricans (90–99 years old). Younger age and being female—but not education—were associated with better performance on some neuropsychological tests, in particular episodic memory. The Puerto Ricans performed better on learning and memory tasks. In cognitively intact Spanish-speaking nonagenarians with little or no education, education did not affect test performance. Additional studies of the effect of education on cognitive performance are warranted in other samples with extremely low education or old age. National differences in performance highlight the importance of group-specific norms.National Institutes of Health/[R21TW009258]/NIH/Estados UnidosUniversidad de Costa Rica/[]/UCR/Costa RicaAlzheimer’s Association/[]//Estados UnidosUCR::Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM)UCR::Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí