The relationship between glycaemia, cognitive function, structural brain outcomes and dementia: A Mendelian randomization study in the UK Biobank

We investigated the relationship between glycaemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomisation (MR). Data were from 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 and white matter hyperintensity volumes, Alzheimer’s 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 reaction time (exponentiated ß=1.00, 95%CI=1.00; 1.00), visual memory (expß=1.00, 95%CI=0.99; 1.00), white matter hyperintensity volume (WMHV) (expß=0.99, 95%CI=0.97; 1.01), hippocampal volume (HV) (ß coefficient mm3=4.56, 95%CI=-3.98; 13.09) or AD (OR 0.89, 95%CI=0.78; 1.01). HbA1c was not associated with RT (expß=1.01, 95%CI=1.00; 1.01), WMHV (expß=0.94, 95%CI=0.81; 1.08), HV (ß=7.21, 95%CI=-54.06; 68.48), or risk of AD (OR 0.94, 95%CI=0.47; 1.86), but HbA1c was associated with visual memory (expß=1.06, 95%CI=1.05; 1.07) using a weighted median. IVW showed that reaction time was not associated with diabetes risk (OR 0.96, 95%CI=0.63; 1.46) or with HbA1c (ß coefficient mmol/mol=-0.08, 95%CI=-0.57; 0.42). Overall, we observed little evidence of causal association between genetic instruments for T2D or peripheral glycaemia and some measures of cognition and brain structure in midlife.

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The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomization Study in the UK Biobank

10.2337/figshare.14096678.v2 ◽

2021 ◽

Author(s):

Victoria Garfield ◽

Aliki-Eleni Farmaki ◽

Ghazaleh Fatemifar ◽

Sophie V. Eastwood ◽

Rohini Mathur ◽

...

Keyword(s):

Type 2 Diabetes ◽

Reaction Time ◽

Cognitive Function ◽

White Matter ◽

Visual Memory ◽

White Matter Hyperintensity ◽

Uk Biobank ◽

The Relationship ◽

Genetic Instruments

We investigated the relationship between glycaemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomisation (MR). Data were from 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 and white matter hyperintensity volumes, Alzheimer’s 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 reaction time (exponentiated ß=1.00, 95%CI=1.00; 1.00), visual memory (expß=1.00, 95%CI=0.99; 1.00), white matter hyperintensity volume (WMHV) (expß=0.99, 95%CI=0.97; 1.01), hippocampal volume (HV) (ß coefficient mm3=4.56, 95%CI=-3.98; 13.09) or AD (OR 0.89, 95%CI=0.78; 1.01). HbA1c was not associated with RT (expß=1.01, 95%CI=1.00; 1.01), WMHV (expß=0.94, 95%CI=0.81; 1.08), HV (ß=7.21, 95%CI=-54.06; 68.48), or risk of AD (OR 0.94, 95%CI=0.47; 1.86), but HbA1c was associated with visual memory (expß=1.06, 95%CI=1.05; 1.07) using a weighted median. IVW showed that reaction time was not associated with diabetes risk (OR 0.96, 95%CI=0.63; 1.46) or with HbA1c (ß coefficient mmol/mol=-0.08, 95%CI=-0.57; 0.42). Overall, we observed little evidence of causal association between genetic instruments for T2D or peripheral glycaemia and some measures of cognition and brain structure in midlife.

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The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomization Study in the UK Biobank

10.2337/figshare.14096678 ◽

2021 ◽

Author(s):

Victoria Garfield ◽

Aliki-Eleni Farmaki ◽

Ghazaleh Fatemifar ◽

Sophie V. Eastwood ◽

Rohini Mathur ◽

...

Keyword(s):

Type 2 Diabetes ◽

Reaction Time ◽

Cognitive Function ◽

White Matter ◽

Visual Memory ◽

White Matter Hyperintensity ◽

Uk Biobank ◽

The Relationship ◽

Genetic Instruments

We investigated the relationship between glycaemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomisation (MR). Data were from 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 and white matter hyperintensity volumes, Alzheimer’s 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 reaction time (exponentiated ß=1.00, 95%CI=1.00; 1.00), visual memory (expß=1.00, 95%CI=0.99; 1.00), white matter hyperintensity volume (WMHV) (expß=0.99, 95%CI=0.97; 1.01), hippocampal volume (HV) (ß coefficient mm3=4.56, 95%CI=-3.98; 13.09) or AD (OR 0.89, 95%CI=0.78; 1.01). HbA1c was not associated with RT (expß=1.01, 95%CI=1.00; 1.01), WMHV (expß=0.94, 95%CI=0.81; 1.08), HV (ß=7.21, 95%CI=-54.06; 68.48), or risk of AD (OR 0.94, 95%CI=0.47; 1.86), but HbA1c was associated with visual memory (expß=1.06, 95%CI=1.05; 1.07) using a weighted median. IVW showed that reaction time was not associated with diabetes risk (OR 0.96, 95%CI=0.63; 1.46) or with HbA1c (ß coefficient mmol/mol=-0.08, 95%CI=-0.57; 0.42). Overall, we observed little evidence of causal association between genetic instruments for T2D or peripheral glycaemia and some measures of cognition and brain structure in midlife.

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The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomization Study in the UK Biobank

10.2337/figshare.14096678.v3 ◽

2021 ◽

Author(s):

Victoria Garfield ◽

Aliki-Eleni Farmaki ◽

Ghazaleh Fatemifar ◽

Sophie V. Eastwood ◽

Rohini Mathur ◽

...

Keyword(s):

Type 2 Diabetes ◽

Reaction Time ◽

Cognitive Function ◽

White Matter ◽

Visual Memory ◽

White Matter Hyperintensity ◽

Uk Biobank ◽

The Relationship ◽

Genetic Instruments

We investigated the relationship between glycaemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomisation (MR). Data were from 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 and white matter hyperintensity volumes, Alzheimer’s 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 reaction time (exponentiated ß=1.00, 95%CI=1.00; 1.00), visual memory (expß=1.00, 95%CI=0.99; 1.00), white matter hyperintensity volume (WMHV) (expß=0.99, 95%CI=0.97; 1.01), hippocampal volume (HV) (ß coefficient mm3=4.56, 95%CI=-3.98; 13.09) or AD (OR 0.89, 95%CI=0.78; 1.01). HbA1c was not associated with RT (expß=1.01, 95%CI=1.00; 1.01), WMHV (expß=0.94, 95%CI=0.81; 1.08), HV (ß=7.21, 95%CI=-54.06; 68.48), or risk of AD (OR 0.94, 95%CI=0.47; 1.86), but HbA1c was associated with visual memory (expß=1.06, 95%CI=1.05; 1.07) using a weighted median. IVW showed that reaction time was not associated with diabetes risk (OR 0.96, 95%CI=0.63; 1.46) or with HbA1c (ß coefficient mmol/mol=-0.08, 95%CI=-0.57; 0.42). Overall, we observed little evidence of causal association between genetic instruments for T2D or peripheral glycaemia and some measures of cognition and brain structure in midlife.

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Relationship Between Type 2 Diabetes and White Matter Hyperintensity: A Systematic Review

Frontiers in Endocrinology ◽

10.3389/fendo.2020.595962 ◽

2020 ◽

Vol 11 ◽

Author(s):

Dan-Qiong Wang ◽

Lei Wang ◽

Miao-Miao Wei ◽

Xiao-Shuang Xia ◽

Xiao-Lin Tian ◽

...

Keyword(s):

Type 2 Diabetes ◽

White Matter ◽

Structural Changes ◽

White Matter Lesions ◽

Poor Performance ◽

White Matter Hyperintensity ◽

Diabetic Microangiopathy ◽

The Relationship ◽

The Brain

White matter (WM) disease is recognized as an important cause of cognitive decline and dementia. White matter lesions (WMLs) appear as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Previous studies have shown that type 2 diabetes (T2DM) is associated with WMH. In this review, we reviewed the literature on the relationship between T2DM and WMH in PubMed and Cochrane over the past five years and explored the possible links among the presence of T2DM, the course or complications of diabetes, and WMH. We found that: (1) Both from a macro- and micro-scopic point of view, most studies support the relationship of a larger WMH and a decrease in the integrity of WMH in T2DM; (2) From the relationship between brain structural changes and cognition in T2DM, the poor performance in memory, attention, and executive function tests associated with abnormal brain structure is consistent; (3) Diabetic microangiopathy or peripheral neuropathy may be associated with WMH, suggesting that the brain may be a target organ for T2DM microangiopathy; (4) Laboratory markers such as insulin resistance and fasting insulin levels were significantly associated with WMH. High HbA1c and high glucose variability were associated with WMH but not glycemic control.

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Postprandial Hyperglycemia Is Associated With White Matter Hyperintensity and Brain Atrophy in Older Patients With Type 2 Diabetes Mellitus

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2018.00273 ◽

2018 ◽

Vol 10 ◽

Cited By ~ 6

Author(s):

Noriko Ogama ◽

Takashi Sakurai ◽

Shuji Kawashima ◽

Takahisa Tanikawa ◽

Haruhiko Tokuda ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

White Matter ◽

Brain Atrophy ◽

Older Patients ◽

Postprandial Hyperglycemia ◽

White Matter Hyperintensity

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Severe tardive dyskinesia induced by domperidone in presenile and non-dementia type 2 diabetes man with alcohol misuse showing albuminocytological dissociation and white matter hyperintensity

BMJ Case Reports ◽

10.1136/bcr-2018-228789 ◽

2019 ◽

Vol 12 (5) ◽

pp. e228789 ◽

Cited By ~ 1

Author(s):

Akinori Kanzaki ◽

Hidetoshi Tada ◽

Akihito Otsuka ◽

Tadashi Nakamura

Keyword(s):

Type 2 Diabetes ◽

White Matter ◽

Tardive Dyskinesia ◽

Blood Brain Barrier ◽

Alcohol Misuse ◽

Brain Barrier ◽

White Matter Hyperintensity ◽

Barrier Dysfunction ◽

Blood Brain

Domperidone has difficulty passing the blood–brain barrier, thus rarely causes tardive dyskinesia. Furthermore, its symptoms in adults are generally mild. Although both alcohol and diabetes are thought to increase the risk of development of tardive dyskinesia, their impact remains controversial, especially diabetes, and factors related to worsened tardive dyskinesia have not been clearly elucidated. A 59-year-old man with type 2 diabetes and history of alcohol misuse, who had been chronically prescribed domperidone at 15 mg/day, showed severe tardive dyskinesia, which was remitted within several days by stopping the drug. In our case, albuminocytological dissociation and white matter hyperintensity on MRI were confirmed, which were thought to be related to blood–brain barrier dysfunction. This present findings indicate that alcohol misuse and type 2 diabetes, as well as albuminocytological dissociation and white matter hyperintensity may result in severe tardive dyskinesia, even in individuals receiving domperidone.

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Sex-Related Differences in Brain Volumes and Cerebral Blood Flow Among Overweight and Obese Adults With Type 2 Diabetes: Exploratory Analyses From the Action for Health in Diabetes Brain Magnetic Resonance Imaging Study

The Journals of Gerontology Series A ◽

10.1093/gerona/glz090 ◽

2019 ◽

Vol 75 (4) ◽

pp. 771-778 ◽

Cited By ~ 2

Author(s):

Mark A Espeland ◽

Kathleen M Hayden ◽

Samuel N Lockhart ◽

Hussein N Yassine ◽

Siobhan Hoscheidt ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

White Matter ◽

Magnetic Resonance ◽

Magnetic Resonance Images ◽

White Matter Hyperintensity ◽

Obese Adults ◽

Brain Volumes

Abstract Background Sex may be an important modifier of brain health in response to risk factors. We compared brain structure and function of older overweight and obese women and men with type 2 diabetes mellitus. Methods Cross-sectional cognitive assessments and magnetic resonance images were obtained in 224 women and 95 men (mean age 69 years) with histories of type 2 diabetes mellitus and overweight or obesity. Prior to magnetic resonance images, participants had completed an average of 10 years of random assignment to either multidomain intervention targeting weight loss or a control condition of diabetes support and education. Total (summed gray and white) matter volumes, white matter hyperintensity volumes, and cerebral blood flow across five brain regions of interest were analyzed using mixed-effects models. Results After covariate adjustment, women, compared with men, averaged 10.9 [95% confidence interval 3.3, 18.5; ≈1%] cc greater summed region of interest volumes and 1.39 [0.00002, 2.78; ≈54%] cc greater summed white matter hyperintensity volumes. Sex differences could not be attributed to risk factor profiles or intervention response. Their magnitude did not vary significantly with respect to age, body mass index, intervention assignment, or APOE-ε4 genotype. Sex differences in brain magnetic resonance images outcomes did not account for the better levels of cognitive functioning in women than men. Conclusions In a large cohort of older overweight or obese adults with type 2 diabetes mellitus, differences in brain volumes and white matter disease were apparent between women and men, but these did not account for a lower prevalence of cognitive impairment in women compared with men in this cohort. Trial registration NCT00017953.

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