184 research outputs found
Recommended from our members
Long-term Glycemic Control and Dementia Risk in Type 1 Diabetes.
ObjectiveIndividuals with type 1 diabetes have experienced an increase in life expectancy, yet it is unknown what level of glycemic control is ideal for maintaining late-life brain health. We investigated the association of long-term glycemic control with dementia in older individuals with type 1 diabetes.Research design and methodsWe followed 3,433 members of a health care system with type 1 diabetes, aged ≥50 years, from 1996 to 2015. Repeated measurements of hemoglobin A1c (HbA1c), dementia diagnoses, and comorbidities were ascertained from health records. Cox proportional hazards models were fit to evaluate the association of time-varying glycemic exposure with dementia, with adjustment for age, sex, race/ethnicity, baseline health conditions, and frequency of HbA1c measurement.ResultsOver a mean follow-up of 6.3 years, 155 individuals (4.5%) were diagnosed with dementia. Patients with ≥50% of HbA1c measurements at 8-8.9% (64-74 mmol/mol) and ≥9% (≥75 mmol/mol) had 65% and 79% higher risk of dementia, respectively, compared with those with <50% of measurements exposed (HbA1c 8-8.9% adjusted hazard ratio [aHR] 1.65 [95% CI 1.06, 2.57] and HbA1c ≥9% aHR 1.79 [95% CI 1.11, 2.90]). By contrast, patients with ≥50% of HbA1c measurements at 6-6.9% (42-52 mmol/mol) and 7-7.9% (53-63 mmol/mol) had a 45% lower risk of dementia (HbA1c 6-6.9% aHR 0.55 [95% CI 0.34, 0.88] and HbA1c 7-7.9% aHR 0.55 [95% CI 0.37, 0.82]).ConclusionsAmong older patients with type 1 diabetes, those with majority exposure to HbA1c 8-8.9% and ≥9% had increased dementia risk, while those with majority exposure to HbA1c 6-6.9% and 7-7.9% had reduced risk. Currently recommended glycemic targets for older patients with type 1 diabetes are consistent with healthy brain aging
Cognitive dysfunction in diabetes: how to implement emerging guidelines
Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognised as an important comorbidity and complication of diabetes that affects an individual's well-being and diabetes management, and is associated with diabetes treatment-related complications. Recent guidelines therefore recommend screening for cognitive impairment in older individuals with diabetes. In addition, these guidelines suggest that glucose-lowering treatment should be tailored in those diagnosed with cognitive impairment, to reduce the risk of hypoglycaemia and improve treatment adherence. This review gives an overview of cognitive dysfunction in people with diabetes, briefly describing the clinical features of different stages of cognitive dysfunction and their epidemiology. In particular, it addresses essential additional steps that need to be taken to fully implement the emerging guidelines on screening and management of cognitive dysfunction in diabetes into daily practice
Sex, Diabetes Status and Cognition: Findings from the Study of Longevity in Diabetes
INTRODUCTION: Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.
RESEARCH DESIGN AND METHODS: We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D (n=232) and without either T1D or T2D (n=247). We used factor analysis to generate summary scores of cognitive domains and used regression analyses to examine the associations between sex and cognition adjusting for sociodemographic and cardiovascular confounders.
RESULTS: We included 1237 participants (630 women and 607 men) with mean age 68 years. By design, the distribution of men and women in T1D, T2D and no diabetes was similar. Women had better cognitive performance than men in global cognition (β=0.21, 95% CI 0.16 to 0.26), language (β=0.08, 95% CI 0.004 to 0.15), executive function (β=0.13, 95% CI 0.05 to 0.20), episodic verbal memory (β=0.68, 95% CI 0.59 to 0.77) and attention (β=0.20, 95% CI 0.11 to 0.28) but not in episodic visual memory (β=0.006, 95% CI -0.07 to 0.09) adjusting for age and education independent of diabetes status. We did not find an interaction between sex and diabetes status for any of the cognitive outcomes.
CONCLUSIONS: Women in late mid-life have better cognitive performance than men in many cognitive domains independent of the presence of T1D or T2D. Further work is required to understand whether these differences change over time or in older cohorts and to understand their relationship to subsequent dementia
Recommended from our members
Development of a machine learning algorithm to predict the residual cognitive reserve index
Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an MRI-based residual approach. An eXtreme Gradient Boosting machine learning algorithm was trained to predict this residual reserve index (RRI) using three models: Minimal (basic clinical data, such as age, education, anthropometrics, and blood pressure), Extended (Minimal model plus cognitive screening, word reading, and depression measures), and Full [Extended model plus Clinical Dementia Rating (CDR) and Everyday Cognition (ECog) scale]. External validation was performed in an independent sample of ADNI 1/3/GO participants (N = 1640), which examined whether the effects of brain change on cognitive change were moderated by the machine learning models' cognitive reserve estimates. The three machine learning models differed in their accuracy and validity. The Minimal model did not correlate strongly with the criterion standard (r = 0.23) and did not moderate the effects of brain change on cognitive change. In contrast, the Extended and Full models were modestly correlated with the criterion standard (r = 0.49 and 0.54, respectively) and prospectively moderated longitudinal brain-cognition associations, outperforming other cognitive reserve proxies (education, word reading). The primary difference between the Minimal model-which did not perform well as a measure of cognitive reserve-and the Extended and Full models-which demonstrated good accuracy and validity-is the lack of cognitive performance and informant-report data in the Minimal model. This suggests that basic clinical variables like anthropometrics, vital signs, and demographics are not sufficient for estimating cognitive reserve. Rather, the most accurate and valid estimates of cognitive reserve were obtained when cognitive performance data-ideally augmented by informant-reported functioning-was used. These results indicate that a dynamic and accessible proxy for cognitive reserve can be generated for individuals without neuroimaging data and gives some insight into factors that may promote resilience
Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis
Objective To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases
rPOP: Robust PET-Only Processing of Community Acquired Heterogeneous Amyloid-PET Data
The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (18F-florbetapir/FBP, 18F-florbetaben/FBB or 18F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with the image as it is. We validate rPOP with n = 740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the Imaging Dementia—Evidence for Amyloid Scanning – Brain Health Registry sub-study (IDEAS-BHR) and n = 1,518 scans from the Alzheimer\u27s Disease Neuroimaging Initiative (n = 1,249 FBP, n = 269 FBB), including heterogeneous acquisition and reconstruction protocols. After running rPOP, a standard quantification to extract Standardized Uptake Value ratios and the respective Centiloids conversion was performed. rPOP-based amyloid status (using an independent pathology-based threshold of ≥24.4 Centiloid units) was compared with either local visual reads (IDEAS-BHR, n = 663 with complete valid data and reads available) or with amyloid status derived from an MRI-based PET processing pipeline (ADNI, thresholds of \u3e20/\u3e18 Centiloids for FBP/FBB). Finally, within the ADNI dataset, we tested the linear associations between rPOP- and MRI-based Centiloid values. rPOP achieved accurate warping for N = 2,233/2,258 (98.9%) in the first pass. Of the N = 25 warping failures, 24 were rescued with manual reorientation and origin reset prior to warping. We observed high concordance between rPOP-based amyloid status and both visual reads (IDEAS-BHR, Cohen\u27s k = 0.72 [0.7–0.74], ∼86% concordance) or MRI-pipeline based amyloid status (ADNI, k = 0.88 [0.87–0.89], ∼94% concordance). rPOP- and MRI-pipeline based Centiloids were strongly linearly related (R2:0.95, p\u3c0.001), with this association being significantly modulated by estimated PET resolution (β= -0.016, p\u3c0.001). rPOP provides reliable MRI-free amyloid-PET warping and quantification, leveraging widely available software and only requiring an attenuation-corrected amyloid-PET image as input. The rPOP pipeline enables the comparison and merging of heterogeneous datasets and is publicly available at https://github.com/leoiacca/rPO
Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis.
IMPORTANCE: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets. OBJECTIVE: To identify novel genetic loci and pathways associated with AS. DESIGN, SETTING, AND PARTICIPANTS: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019. EXPOSURES: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples. MAIN OUTCOMES AND MEASURES: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography. RESULTS: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]). CONCLUSIONS AND RELEVANCE: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target
Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging
http://deepblue.lib.umich.edu/bitstream/2027.42/55438/1/Haan M, Homocysteine, b vitamins, and the incidence of dementia, 2007.pd
World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia
© 2020 The Authors. Alzheimer\u27s & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer\u27s Association Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer\u27s disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline—from at-risk asymptomatic states to early symptomatic stages—in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies
- …