| Title: | Relationship Between Glycemia and Cognitive Function, Structural Brain Outcomes, and Dementia: A Mendelian Randomization Study in the UK Biobank. |
| Journal: | Diabetes |
| Published: | 15 Jun 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33632741/ |
| DOI: | https://doi.org/10.2337/db20-0895 |
| URL: | https://diabetesjournals.org/diabetes/article-pdf/70/10/2313/628539/db200895.pdf |
| Citations: | 29 (19 in last 2 years) as of 8 Aug 2024 |
Publication 5882
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
We investigated the relationship between glycemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomization (MR). Data were from the UK Biobank (n = ∼500,000). Our exposures were genetic instruments for type 2 diabetes (157 variants) and HbA1c (51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal volume (HV), white matter hyperintensity volume (WMHV), and Alzheimer dementia (AD). We also investigated associations between genetic variants for RT (43 variants) and diabetes and HbA1c We used conventional inverse-variance-weighted (IVW) MR alongside MR sensitivity analyses. Using IVW, genetic liability to type 2 diabetes was not associated with RT (exponentiated β [expβ] = 1.00 [95% CI 1.00; 1.00]), visual memory (expβ = 1.00 [95% CI 0.99; 1.00]), WMHV (expβ = 0.99 [95% CI 0.97; 1.01]), HV (β-coefficient mm3 = -2.30 [95% CI -12.39; 7.78]) or AD (odds ratio [OR] 1.15 [95% CI 0.87; 1.52]). HbA1c was not associated with RT (expβ = 1.00 [95% CI 0.99; 1.02]), visual memory (expβ = 0.99 [95% CI 0.96; 1.02]), WMHV (expβ = 1.03 [95% CI 0.88; 1.22]), HV (β = -21.31 [95% CI -82.96; 40.34]), or risk of AD (OR 1.09 [95% CI 0.42; 2.83]). IVW showed that reaction time was not associated with diabetes risk (OR 0.94 [95% CI 0.54; 1.65]), or with HbA1c (β-coefficient mmol/mol = -0.88 [95% CI = -1.88; 0.13]) after exclusion of a pleiotropic variant. Overall, we observed little evidence of causal association between genetic instruments for type 2 diabetes or peripheral glycemia and some measures of cognition and brain structure in midlife.</p>
23 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Blood Glucose
- Brain
- Cognition
- Dementia
- Diabetes Mellitus, Type 2
- Female
- Genome-Wide Association Study
- Glycated Hemoglobin
- Humans
- Male
- Memory
- Mendelian Randomization Analysis
- Middle Aged
- Organ Size
- Polymorphism, Single Nucleotide
- Prognosis
- Reaction Time
- Risk Factors
- United Kingdom
- White Matter
10 Authors
- Victoria Garfield
- Aliki-Eleni Farmaki
- Ghazaleh Fatemifar
- Sophie V Eastwood
- Rohini Mathur
- Christopher T Rentsch
- Spiros Denaxas
- Krishnan Bhaskaran
- Liam Smeeth
- Nish Chaturvedi
Enabling scientific discoveries that improve human health