Cerebral perfusion in relation to cognitive function and type 2 diabetes.
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ABSTRACT:
SUBMITTER: Tiehuis AM
PROVIDER: S-EPMC2440938 | biostudies-other | 2008 Jul
REPOSITORIES: biostudies-other
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Project description:To explore the effect of T2DM on cerebral perfusion, and the relationship between cerebral perfusion changes and cognitive impairment as well as diabetic variables, by using a whole-brain arterial spin-labeling (ASL) MRI technique. This prospective study was approved by the local institutional review board and was performed between November 2012 and October 2013. All subjects provided informed consent. Forty T2DM patients and 41 age-, sex- and education-matched healthy controls were included. Cerebral blood flow (CBF) map was obtained by pulsed ASL perfusion imaging at 3 T MRI. Voxel-wise comparisons on CBF maps with and without partial volume effects (PVEs) correction were performed between groups. Associations between CBF and cognitive functioning, and between CBF and diabetic variables were investigated by using voxel-wise, whole-brain correlation analyses. In T2DM patients, PVEs uncorrected CBF was decreased in the posterior cingulate cortex (PCC), precuneus and bilateral occipital lobe, and increased in the anterior cingulate cortex (corrected P < .05). These changes were largely unchanged after PVEs correction. Correlation analyses revealed that in patients, hypoperfusion in PCC and precuneus regions were related to higher insulin resistance level and deficits in clock-drawing performance, while the occipital hypoperfusion was associated with worse visual-memory performance, regardless of PVEs correction. The cerebral hypoperfusion pattern in T2DM resembles the pattern observed in the early stage of dementia, and increased insulin resistance might be an important risk factor as well as treatment target for such CBF dysregulation.
| S-EPMC5653700 | biostudies-literature
Project description:AimCerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles' association with SVD.MethodsThis cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA1c 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts).ResultsSVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74-83], 75 [70-80], and 75 [72-81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46-2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy.ConclusionsAlthough the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.
| S-EPMC10148779 | biostudies-literature
Project description:BackgroundCognitive function among apparently healthy adolescents has been associated with cardiovascular morbidity and mortality. We examined the relationship between global and subdomain cognitive scores in adolescence and early-onset type 2 diabetes (T2D) in men and women.MethodsA nationwide, population-based study of 971,677 Israeli born adolescents (56% men; mean age 17.4 years) who were medically examined and their cognitive performance was assessed before compulsory military service during 1992-2010. Data included global and subdomain cognitive Z-scores (problem-solving, verbal abstraction and categorization, verbal comprehension, and mathematical abilities). Data were linked to the Israeli National Diabetes Registry. The relations between global and subdomain scores and incident T2D was determined using Cox proportional hazard models and logistic regression models. Analyses were conducted separately for men and women.FindingsDuring 16,095,122 person-years, 3,570 individuals developed T2D. After adjustment, those in the low compared to the high quintile of global cognitive Z-score had the highest risk for T2D; HR 2.46, (95% CI 2.10-2.88) for men and 2.33 (95% CI 1.88-2.89) for women. A one-unit lower global cognitive Z-score was associated with 1.41 (95% CI 1.34-1.48) and 1.46 (95% CI 1.36-1.56) increased risks for men and women, respectively. The relationship was noted for the cognitive subdomains scores as well as for the global cognitive score, with no heterogeneity across cognitive subdomains.InterpretationThis large nationally representative cohort suggests relationship between global, as well as subdomain cognitive scores in late adolescence, and incident early onset T2D in both sexes, which was independent of socioeconomic status.
| S-EPMC8479622 | biostudies-literature
Project description:Objective:To test whether cognitive function is impaired in early states of diabetes and to identify possible risk factors for cognitive impairment. Methods:A cross-sectional analysis within the German Diabetes Study included patients with type 1 or type 2 diabetes within the first year after diagnosis or five years after study inclusion and metabolically healthy individuals. Participants underwent comprehensive metabolic phenotyping and testing of different domains of cognitive function. Linear regression models were used to compare cognition test outcomes and to test associations between cognitive function and possible influencing factors within the groups. Results:In participants with recently diagnosed diabetes, verbal memory was poorer in patients with type 2 diabetes (P = 0.029), but not in type 1 diabetes (P = 0.156), when compared to healthy individuals. Five years after diagnosis, type 2 diabetes patients also showed lower verbal memory than those with type 1 diabetes (P = 0.012). In addition to crystallized intelligence, a higher body mass index among individuals with recently diagnosed type 2 diabetes and male sex among individuals with recently diagnosed type 1 diabetes were associated with impaired verbal memory (all P < 0.05). Conclusion:Verbal memory is impaired in individuals with recently diagnosed type 2 diabetes and likely associated with higher body mass. This trial is registered with the trial registration number NCT01055093.
| S-EPMC6109580 | biostudies-literature
Project description:Subcortical ischemic vascular disease (SIVD) is one of the important causes of cognitive dysfunction, altered amyloid-beta (Aβ) and cerebral perfusion may be involved in the pathophysiological mechanism of SIVD and are closely related to cognitive function. We aimed to investigate altered serum Aβ and cerebral perfusion in patients with SIVD and their correlation with cognitive function. Seventy-four healthy controls (HCs) and 74 SIVD patients, including 38 SIVD patients with no cognitive impairment (SIVD-NCI) and 36 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the measurement of serum Aβ40 and Aβ42 levels, pseudo-continuous arterial spin labeling MRI scanning, and cognitive evaluation. Compared to the healthy controls (HCs), the level of serum Aβ40 and Aβ40/42 ratio increased and Aβ42 decreased in SIVD patients. The serum Aβ40 level and Aβ40/42 ratio in patients with SIVD-MCI were significantly higher than those in the HCs and SIVD-NCI, and the level of Aβ42 in the SIVD-MCI was lower than the HCs. In addition, the serum Aβ40/42 ratio provided high diagnostic accuracy for SIVD and SIVD-MCI, it was further identified as an independent risk factor for cognitive impairment. Patients with SIVD-NCI and SIVD-MCI exhibited both increased and decreased cerebral blood flow (CBF) in regional. The Aβ40/42 ratio was associated with global CBF, while altered global and regional CBF was associated with cognitive deficits. In addition, white matter hyperintensities volume (WMHV) correlated with Aβ40/42 ratio, CBF, and cognition. The relationship between Aβ40/42 ratio and cognition was partially mediated by altered CBF. Based on these results, we conclude that the serum Aβ40/42 ratio may be a potential biomarker that can complement current methods for the prediction and diagnosis of cognitive impairment in SIVD patients. In addition, serum Aβ may play a role in cognitive function by regulating CBF, which provides new insights into the intervention, treatment, and prevention of cognitive impairment in SIVD.
| S-EPMC9608371 | biostudies-literature
Project description:Background:African Americans typically perform worse than European Americans on cognitive testing. Contributions of cardiovascular disease (CVD) risk factors and educational quality to cognitive performance and brain volumes were compared in European Americans and African Americans with type 2 diabetes. Methods:Association between magnetic resonance imaging-determined cerebral volumes of white matter (WMV), gray matter (GMV), white matter lesions (WMLV), hippocampal GMV, and modified mini-mental state exam (3MSE), digit symbol coding (DSC), Rey Auditory Verbal Learning Test (RAVLT), Stroop, and verbal fluency performance were assessed in Diabetes Heart Study Memory in Diabetes (MIND) participants. Marginal models incorporating generalized estimating equations were employed with serial adjustment for risk factors. Results:The sample included 520 African Americans and 684 European Americans; 56 per cent female with mean ± SD age 62.8 ± 10.3 years and diabetes duration 14.3 ± 7.8 years. Adjusting for age, sex, diabetes duration, BMI, HbA1c, total intracranial volume, scanner, statins, CVD, smoking, and hypertension, WMV (p = .001) was lower and WMLV higher in African Americans than European Americans (p = .001), with similar GMV (p = .30). Adjusting for age, sex, education, HbA1c, diabetes duration, hypertension, BMI, statins, CVD, smoking, and depression, poorer performance on 3MSE, RAVLT, and DSC were seen in African Americans (p = 6 × 10-23-7 × 10-62). Racial differences in cognitive performance were attenuated after additional adjustment for WMLV and nearly fully resolved after adjustment for wide-range achievement test (WRAT) performance (p = .0009-.65). Conclusions:African Americans with type 2 diabetes had higher WMLV and poorer cognitive performance than European Americans. Differences in cognitive performance were attenuated after considering WMLV and apparent poorer educational quality based on WRAT.
| S-EPMC5861881 | biostudies-other
Project description:To test associations between statin use and cognitive impairment in adults with childhood-onset type 1 diabetes (T1D).In 2010-13, n = 108 middle-aged participants from ongoing observational Pittsburgh Epidemiology of Diabetes Complications Study underwent neurocognitive assessment (mean age and T1D duration of 49 and 41 years, respectively). All were diagnosed with childhood-onset (i.e., prior to age 18) T1D between 1950 and 1980 and were seen within one year of diagnosis at Children's Hospital of Pittsburgh. Self-reported statin use (yes/no and if yes, name of statin) was collected biennially from parent study baseline (1986-1988) to time of neurocognitive testing. Logistic regression models tested associations between statin use groups and cognitive impairment (defined as having two or more cognitive test scores 1.5SD or worse than published norms) while linear regression models tested associations between statin use groups and cognitive domain z-scores (domains: Verbal IQ, memory, executive function, psychomotor speed, and visuo-construction). All models controlled for education and age. To address confounding by indication, models were repeated using a propensity score for statin use.Of the 108 participants, 51 reported never using statins. Median duration of statin use among the 57 ever users was 6 years. These 57 ever statin users were split to create two groups (≤ or > median years of statin use): 1-6 years (n = 25), and 7-12 years (n = 32). Compared with never users, using statins 1-6 years tripled the odds of cognitive impairment (OR = 3.16; 95%CI: 0.93-10.72; P = 0.06) and using statins 7-12 years almost quintupled the odds of cognitive impairment (OR = 4.84; 95%CI: 1.63-14.44; P = 0.005). Compared with never users, using statins 1-6 or 7-12 years was related to worse performance in the memory domain (β = -0.52; P = 0.003, and -0.39; P = 0.014, respectively). Adjusting for coronary artery disease, low density lipoprotein cholesterol, and Apo E4 status did not substantially alter results, and none of these covariates were significantly related to cognitive outcomes (all P > 0.05). Propensity score analyses support that associations between poor cognitive outcomes and statin use were not due merely to confounding by indication.Statin use was associated with cognitive impairment, particularly affecting memory, in these middle-aged adults with childhood-onset T1D, whom at this age, should not yet manifest age-related memory deficits.
| S-EPMC5483427 | biostudies-other
Project description:BackgroundFew data on the pathology of cerebral vessel disease, dementia, and cognition are available. We examined the association of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer's disease dementia and cognitive function.MethodsThis cross-sectional study included men and women aged 65 years or older who had yearly clinical assessments and had agreed to brain autopsy at the time of death, as part of one of two cohort studies of ageing (The Religious Orders Study and the Rush Memory and Aging Project). Individuals without dementia or with Alzheimer's disease dementia, and with complete neuropathological data, are included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Clinical data recorded between 1994 and 2015 were used to determine presence of Alzheimer's disease dementia. Systematic neuropathological assessments documented the severity of cerebral large vessel (atherosclerosis) and small vessel (arteriolosclerosis) disease. By use of regression analyses adjusted for demographics, gross and microscopic infarcts, and Alzheimer's disease pathology, we examined associations of vessel disease severity (mild, moderate, and severe) with odds of probable and possible Alzheimer's disease dementia and cognitive function.FindingsStudy enrolment began in January, 1994, and two cohort studies are ongoing. 1143 individuals were included in our analyses (median age at death 88·8 years; 478 [42%] with Alzheimer's disease dementia). Moderate-to-severe atherosclerosis was present in 445 (39%) individuals, and arteriolosclerosis in 401 (35%) individuals. Each level increase in the severity of atherosclerosis or arteriolosclerosis was associated with significantly higher odds of Alzheimer's disease dementia (odds ratio [OR] for atherosclerosis 1·33, 95% CI 1·11-1·58; OR for arteriolosclerosis 1·20, 1·04-1·40). Atherosclerosis was associated with lower scores for global cognition (estimate -0·10 [SE 0·04], p=0·0096) and four cognitive domains (episodic memory -0·10 [0·04], p=0·017; semantic memory -0·11 [0·05], p=0·018; perceptual speed -0·14 [0·04], p=0·00080; and visuospatial abilities -0·13 [0·04], p=0·0080), but not working memory (-0·05 [0·04], p=0·21). Arteriolosclerosis was associated with lower scores for global cognition (estimate -0·10 [0·03], p=0·0015) and four domains (episodic memory -0·12 [0·04], p=0·00090; semantic memory -0·10 [0·04], p=0·013; working memory -0·07 [0·03], p=0·045; perceptual speed -0·12 [0·04], p=0·0012), and a non-significant association was noted for visuospatial abilities (-0·07 [0·03], p=0·052). Findings were unchanged in analyses controlling for the presence of APOE ε4 allele or vascular risk factors.InterpretationCerebral atherosclerosis and arteriolosclerosis are associated with Alzheimer's disease dementia, and are also associated with low scores in most cognitive domains. Cerebral vessel pathology might be an under-recognised risk factor for Alzheimer's disease dementia.FundingUS National Institutes of Health.
| S-EPMC4969105 | biostudies-literature
Project description:ObjectivePatients with type 1 diabetes now live long enough to experience cognitive decline. During middle age, they show mild cognitive deficits, but it is unknown whether severity increases with aging or whether cognitive profiles are similar to those of age-matched peers with and without diabetes.Research design and methodsWe tested and compared cognition in 82 individuals with 50 or more years of type 1 diabetes (Medalists), 31 age-matched individuals with type 2 diabetes, and 30 age-matched control subjects without diabetes. Medical histories and biospecimens were collected. We also evaluated the association of complications with cognition in Medalists only.ResultsCompared with control subjects, both individuals with type 1 diabetes and individuals with type 2 diabetes performed worse on immediate and delayed recall (P ≤ 0.002) and psychomotor speed in both hands (P ≤ 0.01) and showed a trend toward worse executive function (P = 0.05). In Medalists, cardiovascular disease was associated with decreased executive function and proliferative diabetic retinopathy with slower psychomotor speed.ConclusionsBoth patients with type 1 and patients with type 2 diabetes showed overall worse cognition than control subjects. Further, in Medalists, a relationship between complications and cognition was seen. Although both groups with diabetes showed similar deficit patterns, the underlying mechanisms may be different. Now that patients with type 1 diabetes are living longer, efforts should be made to evaluate cognition and to identify modifying behaviors to slow decline.
| S-EPMC6054500 | biostudies-literature
Project description:ObjectiveCognitive impairments in type 1 diabetes may result from hyperglycemia-associated cerebral microangiopathy. We aimed to identify cerebral microangiopathy and skin microvascular dysfunction-as a surrogate marker for generalized microvascular function-as predictors of cognitive performance over time.MethodsIn this prospective cohort study, 25 type 1 diabetes patients with proliferative retinopathy and 25 matched healthy controls underwent neurocognitive testing at baseline and after follow-up (3.8 ± 0.8 years). At baseline, 1.5-T cerebral magnetic resonance imaging was used to detect WML and cerebral microbleeds. Skin capillary perfusion was assessed by means of capillary microscopy.ResultsIn type 1 diabetes patients, but not in healthy controls, the presence of WML (ß = -0.419; P = 0.037) as well as lower skin capillary perfusion (baseline: ß = 0.753; P < 0.001; peak hyperemia: ß = 0.743; P = 0.001; venous occlusion: ß = 0.675; P = 0.003; capillary recruitment: ß = 0.549; P = 0.022) at baseline was associated with lower cognitive performance over time, independent of age, sex, HbA1c, and severe hypoglycemia. The relationship between WML and lower cognitive performance was significantly reduced after adjusting for capillary perfusion.ConclusionsThese data fit the hypothesis that cerebral microangiopathy is a manifestation of generalized microvascular dysfunction, leading to lower cognitive performance.
| S-EPMC6593465 | biostudies-literature