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1.
Int Psychogeriatr ; 31(4): 591-595, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30526693

ABSTRACT

Depression and cognitive impairment are highly prevalent in type 2 diabetes (T2D), yet little is known about how their relationship varies by sex. We examined this question in a large T2D sample (N = 897) of non-demented elderly (≥ 65) participating in the Israel Diabetes and Cognitive Decline (IDCD) Study. Cognition was evaluated by a comprehensive neuropsychological battery and depressive symptoms were assessed by the Geriatric Depression Scale (GDS). The results showed that in all but the executive function domain, the association of depressive symptoms with poorer cognitive function was stronger in women than men, with a significant interaction for language/semantic categorization and missed significance for episodic memory. When defining clinical depression as GDS of ≥6, women with depression had significantly poorer language/semantic categorization, episodic memory, and overall cognitive function. Inclusion of antidepressants in the model did not alter substantively the associations. Our results suggest that depressed T2D women may have poorer cognitive performance, highlighting the significance of sex-specific personalized management of depression in elderly diabetics.

2.
Int J Geriatr Psychiatry ; 31(5): 494-501, 2016 May.
Article in English | MEDLINE | ID: mdl-26388309

ABSTRACT

OBJECTIVE: The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function. METHODS: This cross-sectional study evaluated 787 cognitively normal older individuals (>65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education. RESULTS: Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant. CONCLUSIONS: Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African-Americans and Hispanics.


Subject(s)
Cognition/physiology , Diabetes Mellitus, Type 2 , Haptoglobins/genetics , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Attention/physiology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/physiopathology , Executive Function/physiology , Female , Genotype , Humans , Jews , Male , Memory, Short-Term/physiology , Middle Aged , Phenotype , Sex Factors
3.
Alzheimers Dement ; 12(8): 925-9, 2016 08.
Article in English | MEDLINE | ID: mdl-27149905

ABSTRACT

INTRODUCTION: Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood. METHODS: We studied the relationship of waist circumference with five cognitive outcomes (executive functioning, language/semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 845 cognitively normal elderly with type 2 diabetes (T2D). RESULTS: In women, waist circumference was correlated with significantly lower language and/or semantic categorization performance (P < .0001), executive functioning (P = .026), and overall cognition (P = .003) after controlling for age, education, BMI, and cardiovascular, diabetes-related, APOE ε4, and inflammatory potential confounders. Attention/working memory (P = .532) and episodic memory (P = .144) were not associated with waist circumference. These correlations were not found in men. DISCUSSION: These results suggest that central adiposity in elderly women with T2D may increase their risk for dementia.


Subject(s)
Aging , Cognition Disorders/etiology , Diabetes Mellitus, Type 2/complications , Sex Characteristics , Waist Circumference/physiology , Aged, 80 and over , Female , Humans , Male , Risk Factors
4.
J Cross Cult Gerontol ; 31(2): 129-41, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26883764

ABSTRACT

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.


Subject(s)
Aging/psychology , Cognition/physiology , Cross-Cultural Comparison , Educational Status , Hispanic or Latino/psychology , Hispanic or Latino/statistics & numerical data , Neuropsychological Tests/statistics & numerical data , Age Factors , Aged, 80 and over , Costa Rica , Education , Female , Humans , Male , Psychiatric Status Rating Scales , Puerto Rico , Sex Factors
5.
Diabetologia ; 58(4): 736-44, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25628235

ABSTRACT

AIMS/HYPOTHESIS: The purpose of this study was to investigate whether the association of glycaemic control with cognitive function is modulated by the haptoglobin 1-1 (Hp 1-1) genotype in cognitively normal elderly individuals with type 2 diabetes. METHODS: In this cross-sectional study, we examined 793 participants who were genotyped for Hp (80 Hp 1-1 carriers and 713 Hp 1-1 non-carriers) enrolled in the Israel Diabetes and Cognitive Decline (IDCD) study. Glycaemic control was operationally defined by HbA1c level. The outcome measures were performance in four cognitive domains (episodic memory, attention/working memory, language/semantic categorisation, executive function) and overall cognition, a composite of the domains. Effect sizes were obtained from hierarchical linear regression analyses for each outcome measure, controlling for demographics, type 2 diabetes-related characteristics, cardiovascular risk factors, and their interactions with Hp genotype. RESULTS: Interaction analyses showed significantly stronger associations of HbA1c with poorer cognitive function among Hp 1-1 carriers than non-carriers; attention/working memory (p < 0.001) and overall cognition (p = 0.003). For these two cognitive domains, associations were significant for Hp 1-1 carriers despite the small sample size (p < 0.00001 and p = 0.001, respectively), but not for non-carriers. CONCLUSIONS/INTERPRETATION: Our findings suggest that patients with type 2 diabetes and poor glycaemic control carrying the Hp 1-1 genotype may be at increased risk of cognitive impairment, particularly in the attention/working memory domain. The association of glycaemic control with this domain may indicate cerebrovascular mechanisms.


Subject(s)
Cognition Disorders/genetics , Cognition , Diabetes Mellitus, Type 2/genetics , Glycated Hemoglobin/analysis , Haptoglobins/genetics , Age Factors , Aged , Attention , Biomarkers/blood , Chi-Square Distribution , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/immunology , Executive Function , Female , Genetic Predisposition to Disease , Humans , Israel , Linear Models , Male , Memory, Episodic , Phenotype , Risk Factors
6.
Am J Geriatr Psychiatry ; 22(10): 1055-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24534521

ABSTRACT

OBJECTIVES: It is unclear why duration of type 2 diabetes (T2D) is associated with increased cognitive compromise. High hemoglobin A1c (HbA1c) has also been associated with dementia, and is the primary contributor to T2D complications. Here we investigated whether the association of duration of T2D with cognitive functioning is modulated by HbA1C levels. METHODS: This study examined nondemented community-dwelling T2D elderly (N = 897) participating in the Israel Diabetes and Cognitive Decline study, who were assessed with a broad neuropsychological battery. Subjects were all from the Maccabi Healthcare Services, which has a Diabetes Registry with complete HbA1c measurements since 1998. Partial correlations were performed to examine the modulating effect of HbA1c on the relationship of duration of T2D with five cognitive measures, controlling for sociodemographic and cardiovascular risk factors. RESULTS: An interaction of duration of T2D with HbA1c was associated with executive functioning (p = 0.006), semantic categorization (p = 0.019), attention/working memory (p = 0.011), and overall cognition (p = 0.006), such that the associations between duration of T2D and cognitive impairment increased as HbA1c levels increased-but not for episodic memory (p = 0.984). CONCLUSIONS: Because duration of T2D was associated with cognition in higher HbA1c levels and overall no associations were found in lower HbA1c levels, our results suggest that individuals with T2D may limit their risk of future cognitive decline by maintaining long-term good glycemic control.


Subject(s)
Cognition Disorders/blood , Diabetes Complications/psychology , Diabetes Mellitus, Type 2/psychology , Glycated Hemoglobin/metabolism , Aged , Cognition Disorders/complications , Cohort Studies , Diabetes Complications/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Neuropsychological Tests , Time Factors
7.
J Geriatr Psychiatry Neurol ; 27(4): 266-75, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24759088

ABSTRACT

BACKGROUND: Neuropsychological and depression measures have been found to predict cognitive functioning. We compared these associations among whites and Spanish-speaking Hispanics. METHODS: Fifty-two pairs of whites and Hispanics were matched demographically and clinically in a cross-sectional study. Hierarchical regression analyses predicted Global Deterioration Scale (GDS) rating by baseline neuropsychological tests and depression symptoms. RESULTS: Neuropsychological tests predicted GDS better in whites; depression symptoms--specifically retardation--predicted well in Hispanics but not whites. Immediate recall of the New York University (NYU)-Paragraph Test and the Retardation item of the Hamilton Depression Rating Scale were associated with GDS in Hispanics and delayed recall of the NYU-Paragraph Test and Wechsler Adult Intelligence Scale-Digit Symbol in whites. Neuropsychological tests and depression symptoms predicted GDS differently in Hispanics and whites. DISCUSSION: These results suggest that other measures should be considered to increase the predictive accuracy of neuropsychological tests when assessing cognitive status in Spanish-speaking Hispanics. Additional studies of specific ethnic/racial and sociodemographic subgroups are warranted.


Subject(s)
Cognition Disorders/ethnology , Dementia/ethnology , Depression/ethnology , Hispanic or Latino/psychology , Neuropsychological Tests/standards , White People/psychology , Aged , Aged, 80 and over , Cognition , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Cross-Sectional Studies , Dementia/diagnosis , Dementia/psychology , Depression/diagnosis , Depression/psychology , Educational Status , Female , Humans , Language , Male , Middle Aged , Neuropsychological Tests/statistics & numerical data , New York , Predictive Value of Tests , Psychiatric Status Rating Scales , Regression Analysis
8.
Int J Geriatr Psychiatry ; 29(3): 299-309, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23925856

ABSTRACT

OBJECTIVE: To evaluate the relationships of age, education, and gender with performance on neuropsychological tests in a cognitively intact, older Israeli sample with type 2 diabetes (T2D). METHODS: We examined 862 participants, 65-84 years old, enrolled in the Israel Diabetes and Cognitive Decline study. Multiple regression assessed associations of performance on 17 neuropsychological tests, including the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery, with age, education, and gender. RESULTS: Higher education and younger age were consistently associated with better performance. Women outperformed men on all memory tasks; men outperformed women on two non-verbal measures. These patterns of demographic associations with cognitive performance were very similar to those of US cohorts. CONCLUSIONS: In a cognitively intact, older Israeli sample with T2D, better test performance is associated primarily with higher education, followed by younger age and gender differences. Although T2D is associated with cognitive deficits, it recapitulates the patterns of relationships between cognitive performance and demographic characteristics seen in non-T2D diabetic samples.


Subject(s)
Aging/psychology , Cognition/physiology , Diabetes Mellitus, Type 2/psychology , Age Factors , Aged , Aged, 80 and over , Educational Status , Female , Humans , Israel , Male , Neuropsychological Tests , Regression Analysis , Sex Factors
9.
Diabetes Res Clin Pract ; 195: 110149, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36427629

ABSTRACT

AIMS: This randomized control trial compared an adaptive computerized cognitive training intervention with a non-adaptive version. The primary hypothesis predicted better diabetes self-management in type 2 diabetes patients at 6 months post-intervention than baseline in the adaptive arm, with seven secondary outcomes. METHODS: Intent-to-treat analysis of veterans without dementia aged 55+ from the Bronx, NY and Ann Arbor, MI (N = 90/per arm) used linear mixed model analyses. RESULTS: Contrary to the hypothesis, only memory showed more improvement in the adaptive arm (p < 0.01). Post-hoc analyses combined the two arms; self-management improved at six-months post-intervention (p < 0.001). Memory, executive functions/attention, prospective memory, diastolic blood pressure, and systolic blood pressure improved (p < 0.05); hemoglobin A1c and medication adherence did not improve significantly. CONCLUSIONS: The adaptive computerized cognitive training was not substantially better than non-adaptive, but may improve memory. Post-hoc results for the combined arms suggest computer-related activities may improve diabetes self-management and other outcomes for middle-aged and older patients with type 2 diabetes. Practice effects or awareness of being studied cannot be ruled out.


Subject(s)
Cognitive Dysfunction , Diabetes Mellitus, Type 2 , Self-Management , Veterans , Middle Aged , Humans , Aged , Diabetes Mellitus, Type 2/drug therapy , Cognition , Glycated Hemoglobin , Cognitive Dysfunction/psychology
10.
Am J Geriatr Psychiatry ; 19(4): 357-63, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20808140

ABSTRACT

OBJECTIVE: There is evidence that major depression increases the risk for dementia, but there is conflicting evidence as to whether depression may accelerate cognitive decline in dementia. The authors tested the hypothesis that decline in cognitive function over time is more pronounced in patients with dementia with comorbid depression, when compared with patients with dementia without depression history. DESIGN: Prospective, longitudinal cohort study of aging. SETTING: Nursing home. PARTICIPANTS: Three hundred thirteen elderly nursing home residents (mean age at baseline: 86.99 years, standard deviation = 6.7; 83.1% women). At baseline, 192 residents were diagnosed with dementia, and another 27 developed dementia during follow-up. Thirty residents suffered from major depression at any point during the study, and 48 residents had a history of depression. MEASUREMENTS: The authors measured cognitive decline using change in Mini-Mental State Examination (MMSE) scores over up to 36 months. The authors calculated multilevel regression models to estimate the effects of age, gender, education, dementia status, depression, depression history, and an interaction between dementia and depression, on change in MMSE scores over time. RESULTS: Beyond the effects of age, gender, and education, residents showed steeper cognitive decline in the presence of dementia (ß = -13.69, standard error = 1.38) and depression (ß = -4.16, SE = 1.2), which was further accelerated by the presence of both depression and dementia (ß = -2.72, SE = 0.65). CONCLUSIONS: In dementia, the presence of depression corresponds to accelerated cognitive decline beyond gender and level of education, suggesting a unique influence of depression on the rate of cognitive decline in dementia.


Subject(s)
Cognition Disorders/psychology , Dementia/psychology , Depressive Disorder, Major/psychology , Aged, 80 and over , Aging/psychology , Cognition Disorders/complications , Cohort Studies , Dementia/complications , Depressive Disorder, Major/complications , Female , Humans , Male , Neuropsychological Tests , Psychiatric Status Rating Scales
11.
Int J Geriatr Psychiatry ; 24(12): 1429-37, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19382130

ABSTRACT

BACKGROUND: The mini-mental state exam (MMSE) has been used to address questions such as determination of appropriate cutoff scores for differentiation of individuals with intact cognitive function from patients with dementia and rate of cognitive decline. However, little is known about the relationship of performance in specific cognitive domains to subsequent overall decline. OBJECTIVE: To examine the specific and/or combined contribution of four MMSE domains (orientation for time, orientation for place, delayed recall, and attention) to prediction of overall cognitive decline on the MMSE. METHODS: Linear mixed models were applied to 505 elderly nursing home residents (mean age = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine the relationship between baseline scores of these domains and total MMSE scores over time. RESULTS: Orientation for time was the only domain significantly associated with MMSE decline over time. Combination of poor delayed recall with either attention or orientation for place was associated with significantly increased decline on the MMSE. CONCLUSIONS: The MMSE orientation for time predicts overall decline on MMSE scores over time. A good functioning domain added to good functioning delayed recall was associated with slower rate of decline.


Subject(s)
Aging/psychology , Cognition Disorders/diagnosis , Dementia/diagnosis , Neuropsychological Tests , Aged , Aged, 80 and over , Dementia/psychology , Disease Progression , Female , Geriatric Assessment/methods , Humans , Linear Models , Male , Mental Recall/physiology , Middle Aged , Nursing Homes , Predictive Value of Tests
12.
Alzheimers Dement (N Y) ; 5: 926-932, 2019.
Article in English | MEDLINE | ID: mdl-31890856

ABSTRACT

INTRODUCTION: Associations 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. METHODS: The interaction of mean hemoglobin A1c (average = 9.8%), evaluated over duration (average = 116.8 months), was examined for overall cognition and three cognitive domains in a sample of 150 "young-old" veterans (mean age = 70) with type 2 diabetes. RESULTS: The predicted interactions were significant for overall cognition and attention, but not executive functions/language and memory. DISCUSSION: Findings extend the Protected Survivor Model to a "young-old" sample, from the very old. This model suggests focusing on individuals with good cognition despite prolonged high risk when seeking protective factors.

13.
J Alzheimers Dis ; 69(2): 401-411, 2019.
Article in English | MEDLINE | ID: mdl-31006684

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) is prevalent in the general United States population, and in the veteran population. T2DM has consistently been linked to increased risk for cognitive impairment, dementia, and Alzheimer's disease. Computerized cognitive training (CCT) is practical and inexpensive cognitive interventions that is an alternative to medication. OBJECTIVE: To report the recruitment methods and challenges to date in an ongoing two-site randomized controlled trial (RCT) of CCT on cognitive function and T2DM management in an older non-demented veteran population. METHODS: Veterans are recruited primarily by targeted mailings or by direct contact at clinics and presentations. RESULTS: From 1,459 original contacts, 437 expressed initial interest, 111 provided informed consent, and 97 completed baseline assessments. Participants from the two VA Medical Centers differed in demographics and baseline characteristics. Comparing recruitment methods, the proportion of individuals contacted who were ultimately consented was significantly less from mailings (5%) than other sources (20%), primarily face- to-face clinic visits (χ2 (1) = 38.331, p < 0.001). CONCLUSIONS: Mailings are cost-effective, but direct contact improved recruitment. Not using or lacking access to computers and ineligibility were major reasons for non-participation. Within-site comparisons of demographically diverse sites can address confounding of demographic and other site differences.


Subject(s)
Alzheimer Disease/therapy , Cognitive Behavioral Therapy/methods , Cognitive Dysfunction/therapy , Diabetes Mellitus, Type 2/therapy , Patient Selection , Therapy, Computer-Assisted/methods , Aged , Aged, 80 and over , Alzheimer Disease/epidemiology , Alzheimer Disease/psychology , Cognitive Behavioral Therapy/trends , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/psychology , Female , Humans , Male , Mental Status and Dementia Tests , Middle Aged , Risk Factors , Therapy, Computer-Assisted/trends , United States/epidemiology , United States Department of Veterans Affairs/trends , Veterans
14.
Article in English | MEDLINE | ID: mdl-30809196

ABSTRACT

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.

15.
J Alzheimers Dis ; 65(2): 683-692, 2018.
Article in English | MEDLINE | ID: mdl-30103313

ABSTRACT

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 Memory, 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 < 0.001), and Overall Cognition (p < 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 substantially 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.


Subject(s)
Cognition , Depression/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/psychology , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Prospective Studies
16.
JAMA Netw Open ; 1(7): e184458, 2018 11 02.
Article in English | MEDLINE | ID: mdl-30646354

ABSTRACT

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 of myocardial 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 trial was 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 it was 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 carriers was 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.


Subject(s)
Black or African American/genetics , Cognition Disorders/genetics , Cognition , Diabetes Mellitus, Type 2/genetics , Genotype , Haptoglobins/genetics , Polymorphism, Genetic , Age Factors , Aged , Alleles , Cardiovascular Diseases/genetics , Cognition Disorders/ethnology , Cognition Disorders/etiology , Cohort Studies , Dementia/ethnology , Dementia/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/ethnology , Disease Progression , Female , Humans , Male , Memory , Mental Status and Dementia Tests , Middle Aged , Risk Factors
17.
Diabetes Care ; 40(9): 1187-1193, 2017 09.
Article in English | MEDLINE | ID: mdl-28634202

ABSTRACT

OBJECTIVE: This study aimed to analyze the relationship of variability in hemoglobin A1c (HbA1c) over years with subsequent depressive symptoms. RESEARCH DESIGN AND METHODS: Subjects (n = 837) were participants of the Israel Diabetes and Cognitive Decline (IDCD) study, which aimed to examine the relationship of characteristics of long-term type 2 diabetes with cognitive decline. All pertain to a diabetes registry established in 1998, which contains an average of 18 HbA1c measurements per subject. The results presented here are based on the IDCD baseline examination. Symptoms of depression were assessed using the 15-item version of the Geriatric Depression Scale (GDS). To quantify the association between variability in glycemic control (measured as the SD of HbA1c measurements [HbA1c-SD]) since 1998 with the number of depression symptoms at IDCD baseline, incidence rate ratios (IRRs) and corresponding 95% CIs were estimated via negative binomial regression modeling and used to account for the overdispersion in GDS scores. RESULTS: Subjects' ages averaged 72.74 years (SD 4.63 years), and the mean number of years in the diabetes registry was 8.7 (SD 2.64 years). The mean GDS score was 2.16 (SD 2.26); 10% of subjects had a GDS score ≥6, the cutoff for clinically significant depression. Mean HbA1c significantly correlated with HbA1c-SD (r = 0.6625; P < 0.0001). The SD, but not the mean, of HbA1c measurements was significantly associated with the number of subsequent depressive symptoms. For each additional 1% increase in HbA1c-SD, the number of depressive symptoms increased by a factor of 1.31 (IRR = 1.31 [95% CI 1.03-1.67]; P = 0.03). CONCLUSIONS: Variability in glycemic control is associated with more depressive symptoms.


Subject(s)
Depression/diagnosis , Diabetes Mellitus, Type 2/blood , Glycated Hemoglobin/analysis , Aged , Blood Glucose/analysis , Cross-Sectional Studies , Depression/blood , Depression/complications , Diabetes Mellitus, Type 2/complications , Female , Humans , Israel , Male , Registries
18.
J Alzheimers Dis ; 44(3): 927-35, 2015.
Article in English | MEDLINE | ID: mdl-25374105

ABSTRACT

We studied the relationship of adult body height with five cognitive outcomes (executive functioning, semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 897 cognitively normal elderly with type 2 diabetes. Regression analyses controlling for sociodemographic, cardiovascular, and diabetes-related risk factors and depression demonstrated that in males, shorter stature was associated with poorer executive functioning (p = 0.001), attention/working memory (p = 0.007), and overall cognition (p = 0.016), but not with episodic memory (p = 0.715) or semantic categorization (p = 0.948). No relationship between height and cognition was found for females. In cognitively normal type 2 diabetes male subjects, shorter stature, a surrogate for early-life stress and poor nutrition, was associated with cognitive functions.


Subject(s)
Aging/psychology , Body Height , Cognition Disorders/etiology , Diabetes Mellitus, Type 2/complications , Sex Characteristics , Statistics as Topic , Aged , Attention , Executive Function , Female , Humans , Male , Memory, Short-Term , Neuropsychological Tests
19.
Eur Neuropsychopharmacol ; 24(12): 1961-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24529419

ABSTRACT

Postmortem studies have shown that cerebrovascular disease (CVD) neuropathology occurs frequently in type 2 diabetes (T2D) through mechanisms associated with chronic hyperglycemia such as advanced glycation end-products (AGEs). The involvement of T2D in Alzheimer׳s disease (AD)-type neuropathology has been more controversial. While postmortem data from animal studies have supported the involvement of T2D in AD-type neuropathology through insulin mechanism that may affect the development of neuritic plaques and neurofibrillary tangles (NFTs), findings from postmortem studies in humans, of the association of T2D with AD, have been mainly negative. To complicate matters, medications to treat T2D have been implicated in reduced AD-type neuropathology. In this review we summarize the literature on animal and human postmortem studies of T2D neuropathology, mainly the mechanisms involved in hyperglycemia-related CVD neuropathology and hyperinsulinemia-related AD-type neuropathology.


Subject(s)
Alzheimer Disease/complications , Alzheimer Disease/pathology , Brain/metabolism , Brain/pathology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Insulin/metabolism , Alzheimer Disease/metabolism , Animals , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/metabolism , Cerebrovascular Disorders/pathology , Diabetes Mellitus, Type 2/complications , Humans , Hyperglycemia/complications , Hyperglycemia/pathology , Hyperinsulinism/complications , Hyperinsulinism/pathology
20.
Dement Geriatr Cogn Dis Extra ; 4(1): 103-12, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24926308

ABSTRACT

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.

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