Relationship Between Glycemia and Cognitive Function, Structural Brain Outcomes, and Dementia: A Mendelian Randomization Study in the UK Biobank.
Diabetes
; 70(10): 2313-2321, 2021 10.
Article
in En
| MEDLINE
| ID: mdl-33632741
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 = â¼500,000). 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 ß [expß] = 1.00 [95% CI 1.00; 1.00]), visual memory (expß = 1.00 [95% CI 0.99; 1.00]), WMHV (expß = 0.99 [95% CI 0.97; 1.01]), HV (ß-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 (expß = 1.00 [95% CI 0.99; 1.02]), visual memory (expß = 0.99 [95% CI 0.96; 1.02]), WMHV (expß = 1.03 [95% CI 0.88; 1.22]), HV (ß = -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 (ß-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood Glucose
/
Brain
/
Cognition
/
Dementia
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
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Female
/
Humans
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Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Diabetes
Year:
2021
Type:
Article
Affiliation country:
United kingdom