Article 6 [W7] - Neurocognition and T1D Flashcards
Abstract
Mild cognitive dysfunction is a well-established complication of diabetes and its management, although large numbers of psychologists and health professionals may be unaware of its existence, clinical implications, and etiology.
Drawing on results from key studies, systematic reviews, and meta-analyses, this article delineates the neurocognitive phenotypes characteristic of Type 1 diabetes (T1D) and Type 2 diabetes (T2D), and identifies the most plausible risk factors, both those that may be modifiable, like degree of metabolic control, and those that cannot be changed, like the age when a child or adult is diagnosed.
Most children and adults with T1D typically manifest lower scores on measures of intelligence and academic achievement, attention, psychomotor speed, and executive functions. These effects are especially pronounced in those who develop diabetes early in life, before the age of 6 or 7 years.
Chronically elevated blood glucose values increase the risk of both cognitive dysfunction and microstructural changes in white matter tracts.
Poorer metabolic control accelerates the rate of cognitive decline over time, and research suggests that improving metabolic control may slow the rate of decline.
Psychologists and behavioral scientists can play a key role in preventing the onset of cognitive complications or in ameliorating their severity by implementing behavioral strategies known to increase adherence to medical regimens and improve metabolic control.
Children/Adolescents with T1D
T1D is primarily a disorder in childhood. Not all children are equally affected by diabetes.
When developing diabetes before the age of 6 or 7, they have an elevated risk of mild to moderate severe dysfunction affecting all cognitive domains, including learning and memory. After this age = less severe dysfunction. Young adults diagnosed before the age of 7 were also more likely to show evidence of mild to moderate cerebral atrophy.
IQ even continues to decline somewhat through young adulthood as diabetes duration increases, especially in those with early onset. Unknown however if these changes continue into later adulthood.
Diabetes associated cognitive dysfunction emerges soon after diagnosis. 2 Years after diagnosis developmental delays on tests of intelligence were found for children with onset before the age of 4 showing the greatest delay. Brain volumetric changes are present in younger children
Reduced gray matter volume (GMV) was evident in multiple posterior brain regions, including the cerebellum, whereas increased GMV was seen in multiple prefrontal and temporal regions in children of around 7 years. White matter volumes were unaffected. (white matter refers to areas of myelinated neurons). Surprisingly this difference in volume was not found for older children or even adolescents.
Microstructural abnormalities appear soon after diagnosis. Both white and gray matter microstructural anomalies are more prominent in children and adolescents than are volumetric differences. In adolescents reduced white matter integrity was found in tracts within the superior parietal lobule, the corpus callosum, and the posterior limb of the internal capsule. Reduced gray matter integrity in the thalamus and putamen.
Earlier onset of diabetes, longer exposure to higher glucose levels, and greater variability in blood glucose were all associated with greater microstructural damage, and in turn lower IQ.
All studies have found that the diagnosis of diabetes before the age of 7 is the strongest risk factor for neurocognitive dysfunction in individuals with T1D. These abnormalities appear in patients within 12 to 24 months of diagnosis, suggesting that their emergence is not dependent on extensive exposure to elevated blood glucose levels or on the development of microvascular complications. Also remarkable is the fact that childhood-onset diabetes is not associated with a rapid and continuous decline in cognition over time.
At this time it is not possible to rule out the possibility that severe hypoglycemia may affect brain function and structure in children. Severe hypoglycemia => occurs for example when a diabetes patient experiences high blood glucose levels and then overcorrects that with their next insulin dose. That way they experience a hypoglycemic event. So basically very low blood glucose levels.
Diathesis or vulnerability hypothesis => The onset of diabetes, which is normally accompanied by elevated blood glucose levels, triggers a series of structural and functional changes within the brain and at the blood-brain barrier (BBB). Those events increase the permeability of the BBB to larger molecules and potentially neurotoxins, which in turn alters the milieu interieur of the brain, potentially interfering with the process of normal brain development. The first 4 to 5 years of life are a critical period where multiple brain systems may be especially labile, the resulting alterations in brain organization may induce a diathesis or predisposition that increases the individual’s vulnerability to additional brain insults at any time thereafter.
Adults with T1D
Pattern of mild cognitive dysfunction similar to that seen in children, but with slightly larger effect sizes.
Largest effects were seen for intelligence, psychomotor speed, cognitive flexibility, and executive functioning, attention and visual perceptual skills.
The strongest predictor for the cognitive dysfunction here was the presence of microvascular complications.
Gray matter volumetric reductions appear in multiple brain regions. Reductions in basically all subregions of the frontal lobes, as well as in regions of the insula and lobule of the parietal cortex. Studies about younger and middle aged adults also found gray matter reductions in frontal or parietal lobes.
Lower microstructural integrity was seen in the posterior corona radiata and the optic radiations for middle aged adults with a long history of diabetes.
Synthesis: Just like children, adults with type I diabetes also earn slightly below average verbal IQ scores, and perform more poorly on tests of attention, psychomotor speed, and executive functions, but they retain normal learning and memory skills.
