Progression of brain atrophy and cognitive decline in diabetes mellitus

Elderen, Saskia G. C. van; Roos, Albert de; Craen, Anton J. M. de; Westendorp, Rudi G. J.; Blauw, Gerard J.; Jukema, J. Wouter; Bollen, Edward L.E.M.; Middelkoop, H.A.M.; Buchem, Mark A. van

doi:10.1212/wnl.0b013e3181f25f06

Cited by 188 publications

(158 citation statements)

References 37 publications

(38 reference statements)

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“…The reduction in mean total brain volume is 0.2-0.6 SD units, comparable with 3-5 years of normal aging (16)(17)(18). Longitudinal case-control and population-based studies have demonstrated brain volume loss in patients with diabetes that is similar to or up to three times the atrophy rate of normal aging (16)(17)(18)(19). The loss of brain tissue is most clearly reflected by accelerated expansion of the ventricles (16,17,19).…”

Section: Type 2 Diabetesmentioning

confidence: 76%

“…Most crosssectional studies report an association between brain volume and executive functioning or processing speed (21). One longitudinal study found an association between baseline brain atrophy and decline in immediate memory but not in delayed memory (18). Two studies directly examined whether brain volume mediated the relationship between type 2 diabetes and cognitive dysfunction and reported contrasting results: gray matter volume significantly mediated the relationship with executive functioning and memory in one study (22), but in another study, between-group differences in cognition were largely independent of MRI markers of brain atrophy (19).…”

Section: Type 2 Diabetesmentioning

confidence: 99%

“…The relation between type 2 diabetes and WMH is more controversial. Several studies that assessed WMH volumes with (semi)automated methods reported no difference between patients with type 2 diabetes and control subjects in cross-sectional (18,22,32) or longitudinal analyses (18). Other studies reported that WMH volumes were increased in patients with diabetes (7,17,19,33).…”

Section: Type 2 Diabetesmentioning

confidence: 99%

“…Some studies observe that diabetes-associated cognitive decline is independent of SVD burden (18), whereas others report slight (19) or evident mediation of SVD (infarcts, WMH, but not microbleeds) in the associations of diabetes with memory, processing speed, and executive functioning (33).…”

Section: Type 2 Diabetesmentioning

confidence: 99%

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Brain Changes Underlying Cognitive Dysfunction in Diabetes: What Can We Learn From MRI?

2014

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Diabetes is associated with cognitive dysfunction and an increased risk of dementia. This article addresses findings with brain MRI that may underlie cognitive dysfunction in diabetes. Studies in adults with type 1 diabetes show regional reductions in brain volume. In those with a diabetes onset in childhood, these volume reductions are likely to reflect the sum of changes that occur during brain development and changes that occur later in life due to exposure to diabetes-related factors. Type 2 diabetes is associated with global brain atrophy and an increased burden of small-vessel disease. These brain changes occur in the context of aging and often also in relation to an adverse vascular risk factor profile. Advanced imaging techniques detect microstructural lesions in the cerebral gray and white matter of patients with diabetes that affect structural and functional connectivity. Challenges are to further unravel the etiology of these cerebral complications by integrating findings from different imaging modalities and detailed clinical phenotyping and by linking structural MRI abnormalities to histology. A better understanding of the underlying mechanisms is necessary to establish interventions that will improve long-term cognitive outcomes for patients with type 1 and type 2 diabetes.Interest in the effect of diabetes on the brain is growing. It is now clear that type 1 diabetes is associated with modest decrements in cognitive functioning, which are most marked in patients with an early childhood diabetes onset (1). These decrements in adults with type 1 diabetes are most evident in the domains of general intelligence, psychomotor speed, and mental flexibility (2). On these domains, the magnitude of the decrements is ;0.3 to 0.7 SD units relative to people without diabetes (2). This implies that, on average, the performance of people with diabetes on these domains is at the 30th to the 40th percentile of control values. The progression of cognitive decrements in adults with type 1 diabetes, relative to people without diabetes, is generally slow, except in subgroups of patients with marked microvascular complications, who may show more marked decline (1).Modest decrements in cognitive functioning, evident on the domains of verbal and visual memory, information processing speed, and executive functioning, have also been noted in people with type 2 diabetes across all age groups (3). Similar to type 1 diabetes, effect sizes are small to moderate (0.3 to 0.4 SD units) (4) and follow a slow progression over time, only modestly exceeding the rate of normal aging-related cognitive decline (3). In older people, however, particularly older than the age of 65, type 2 diabetes is also associated with more severe forms of cognitive impairment. Data from large epidemiological surveys link diabetes to an increased dementia risk. A meta-analysis estimated that people with type 2 diabetes have a relative risk of vascular dementia of 2.5 (95% CI 2.1-3.0) and that of Alzheimer disease is 1.5 (95% CI 1.2-1.8) relative to indiv...

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Section: Type 2 Diabetesmentioning

confidence: 76%

Section: Type 2 Diabetesmentioning

confidence: 99%

Section: Type 2 Diabetesmentioning

confidence: 99%

Section: Type 2 Diabetesmentioning

confidence: 99%

See 2 more Smart Citations

Brain Changes Underlying Cognitive Dysfunction in Diabetes: What Can We Learn From MRI?

2014

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“…Furthermore, studies of structural magnetic resonance imaging (MRI) show that in T2D cognitive impairment is associated with greater levels of vascular lesions as well as with brain atrophy [6][7][8][9][10] . Prospective MRI studies also show that in T2D brain atrophy occurs at faster rates than in normal ageing 11,12 , suggesting that T2D accelerates neurodegeneration. Animal studies provide additional evidence to show that inducing T2D/insulin resistance (IR) can promote the pathological changes characteristic of Alzheimer's disease (AD), specifically accumulation of amyloid-beta (Aβ) and tau (see review ref.…”

Section: Growing Evidence Supports the Hypothesis That Type 2 Diabetementioning

confidence: 97%

[P4–134]: Insulin Resistance Is Associated With Reductions in Specific Cognitive Domains and Increases in CSF Tau in Cognitively Normal Adults

Laws

Gaskin

Woodfield

et al. 2017

Alzheimer's & Dementia

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Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstratesEpidemiological studies indicate that Type 2 diabetes (T2D) is associated with an increased risk of dementia [1][2][3][4][5] . Clinical studies using cross-sectional designs support this association by showing that cognition is worse in patients with T2D as compared to matched controls without T2D 6,7 . Furthermore, studies of structural magnetic resonance imaging (MRI) show that in T2D cognitive impairment is associated with greater levels of vascular

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Insulin Receptor and the Pathophysiology of Alzheimer Disease

Zemva

Schubert

2013

Metabolic Syndrome and Neurological Disorders

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Progression of brain atrophy and cognitive decline in diabetes mellitus

Cited by 188 publications

References 37 publications

Brain Changes Underlying Cognitive Dysfunction in Diabetes: What Can We Learn From MRI?

Brain Changes Underlying Cognitive Dysfunction in Diabetes: What Can We Learn From MRI?

[P4–134]: Insulin Resistance Is Associated With Reductions in Specific Cognitive Domains and Increases in CSF Tau in Cognitively Normal Adults

Insulin Receptor and the Pathophysiology of Alzheimer Disease

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