Esther van den Berg

Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: A systematic comparison of their impact on cognition

Vascular risk factors, such as type 2 diabetes mellitus, hypertension, dyslipidemia and obesity, have been associated with an increased risk of cognitive dysfunction, particularly in the elderly. The aim of this systematic review was to compare these risk factors with regard to the nature and magnitude of the associated cognitive decrements. Cross-sectional and longitudinal studies that assessed cognitive functioning in non-demented persons in relation to diabetes/impaired glucose metabolism (k = 36), hypertension (k = 24), dyslipidemia (k = 7) and obesity (k = 6) and that adjusted or matched for age, gender and education were included. When possible, effect sizes (Cohens d) were computed per cognitive domain. Diabetes and hypertension were clearly associated with cognitive decrements; the results for obesity and dyslipidemia were less consistent. Effect sizes were moderate (median approximately -0.3) for all risk factors. Decline was found in all cognitive domains, although the effects on cognitive speed, mental flexibility and memory were most consistent. Methodological aspects of included studies and implications of these findings are discussed.

Cognitive dysfunction in patients with type 2 diabetes.

People with diabetes mellitus are at increased risk of cognitive dysfunction and dementia. This review explores the nature and severity of cognitive changes in patients with type 2 diabetes. Possible risk factors such as hypo‐ and hyperglycemia, vascular risk factors, micro‐ and macrovascular complications, depression and genetic factors will be examined, as well as findings from brain imaging and autopsy studies. We will show that type 2 diabetes is associated with modest cognitive decrements in non‐demented patients that evolve only slowly over time, but also with an increased risk of more severe cognitive deficits and dementia. There is a dissociation between these two ‘types’ of cognitive dysfunction with regard to affected age groups and course of development. Therefore, we hypothesize that the mild and severe cognitive deficits observed in patients with type 2 diabetes reflect separate processes, possibly with different risk factors and aetiologies. Copyright

The Backward Span of the Corsi Block-Tapping Task and Its Association With the WAIS-III Digit Span

The Corsi Block-Tapping Task measures visuospatial short-term and working memory, but a standardized backward condition is lacking. The authors present a standardized backward procedure that was examined in 246 healthy older adults (ages 50 to 92), comparing the results with the Digit Span subtest of the Wechsler Adult Intelligence Scale— Third Edition. Principal component analysis resulted in a two-factor model, dissociating a verbal and a spatial working-memory factor. Also the Corsi backward is not more difficult than the Corsi forward, in contrast to the Digit Span backward that is more difficult than the Digit Span forward. This may suggest that the Corsi Block-Tapping Task backward task relies on processing within working-memorys slave systems, whereas the Digit Span backward also relies on the central executive component of working memory. Finally, regression-based normative data and cutoff scores for older adults are presented for use in clinical practice.

Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes

OBJECTIVE Type 2 diabetes is associated with a moderate degree of cerebral atrophy and a higher white matter hyperintensity (WMH) volume. How these brain-imaging abnormalities evolve over time is unknown. The present study aims to quantify cerebral atrophy and WMH progression over 4 years in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 55 patients with type 2 diabetes and 28 age-, sex-, and IQ-matched control participants had two 1.5T magnetic resonance imaging scans with a 4-year interval. Volumetric measurements of total brain, peripheral cerebrospinal fluid (CSF), lateral ventricles, and WMH were performed with k-nearest neighbor–based probabilistic segmentation. All volumes were expressed as percentage of intracranial volume. Linear regression analyses, adjusted for age and sex, were performed to compare brain volumes between the groups and to identify determinants of volumetric change within the type 2 diabetic group. RESULTS At baseline, patients with type 2 diabetes had a significantly smaller total brain volume and larger peripheral CSF volume than control participants. In both groups, all volumes showed a significant change over time. Patients with type 2 diabetes had a greater increase in lateral ventricular volume than control participants (mean adjusted between-group difference in change over time [95% CI]: 0.11% in 4 years [0.00 to 0.22], P = 0.047). CONCLUSIONS The greater increase in lateral ventricular volume over time in patients with type 2 diabetes compared with control participants shows that type 2 diabetes is associated with a slow increase of cerebral atrophy over the course of years.

A detailed profile of cognitive dysfunction and its relation to psychological distress in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (DM2) is a common metabolic disorder. DM2 is associated with cognitive impairments, and with depressive symptoms, which occur in about one third of patients. In the current study we compared the cognitive profile and psychological well-being of 119 patients with DM2 (mean age: 66 +/- 6; mean duration: 9 +/- 6 years) with 55 age and education matched-control participants. Groups were compared on cognitive performance in five major cognitive domains, psychological wellbeing [assessed by Symptom Checklist (SCL)-90-R and the Beck Depression Inventory (BDI-II)] and abnormalities on brain MRI. We hypothesized an interrelationship between cognition, MRI abnormalities, and psychological well-being. DM2 patients performed significantly worse than controls on cognitive tasks, especially on tasks that required more mental efficiency, although the differences were modest (effect sizes Cohen d < .6). We speculate that DM2 patients have a diminished ability to efficiently process unstructured information. Patients with DM2 had significantly higher scores on the SCL-90-R (p < .001) and on the BDI-II (p < .001) and worse MRI ratings than controls, but psychological distress did not correlate with cognition, MRI ratings or biomedical characteristics. Contrary to our hypothesis, cognitive disturbances and psychological distress thus seem independent symptoms of the same disease.

Accelerated cognitive decline in patients with type 2 diabetes: MRI correlates and risk factors

Type 2 diabetes mellitus is associated with an increased risk of cognitive decline and dementia. We examined brain imaging correlates and vascular and metabolic risk factors of accelerated cognitive decline in patients with type 2 diabetes.

Heart failure and cognitive function in the general population: the Hoorn Study

To examine whether reduced cognitive functioning can be observed in early stages of left ventricular (LV) dysfunction and heart failure.

Presence and progression of white matter hyperintensities and cognition A meta-analysis

Objective: We aimed to quantify the effects of white matter hyperintensities (WMHs) on specific cognitive functions with particular attention to WMH progression and localization. Methods: PubMed (January 1990–July 2013) and bibliographies from included articles were used. Studies that were included (1) used MRI; (2) had a population-based or case-control design with a healthy control group that could be used for analysis; (3) matched/adjusted for age, sex, and education; and (4) addressed ≥1 predefined cognitive domains with ≥1 validated neuropsychological tests. Data were independently extracted by 2 investigators. Pearson r was extracted/calculated and used as the common metric for the effect size across studies. Results: Twenty-three cross-sectional and 14 longitudinal studies were included with a total of 8,685 and 7,731 participants. Presence of WMHs was significantly associated with concurrent cognitive deficits in all examined domains: general intelligence (Fisher z −0.10, 95% confidence interval [CI] −0.19 to −0.04), memory (−0.08, −0.13 to −0.06), processing speed (−0.11, −0.17 to −0.07), attention and executive functions (−0.11, −0.16 to −0.07), and perception/construction (−0.15, −0.21 to −0.07). Similar effect sizes were observed for cognitive decline over time. WMH progression was associated with greater cognitive decline, particularly for general intelligence (Fisher z −0.31, 95% CI −0.5 to −0.02) and attention and executive functions (−0.32, −0.34 to −0.28). Conclusions: The small but robust and consistent effects of WMHs on all cognitive domains suggest a more global effect on cognition than previously thought. Progression of WMHs was associated with even worse cognitive functioning, most pronounced in attention and executive functioning.

Associations between retinal microvascular changes and dementia, cognitive functioning, and brain imaging abnormalities: a systematic review.

Retinal microvascular changes can be visualized noninvasively and have been associated with cognitive decline and brain changes in relation to aging and vascular disease. We systematically reviewed studies, published between 1990 and November 2012, on the association between retinal microvascular changes and dementia, cognitive functioning, and brain imaging abnormalities, in the context of aging and vascular risk factors. In cross-sectional studies (k = 26), retinal microvascular changes were associated with the presence of dementia (range of odds ratios (ORs) 1.17;5.57), with modest decrements in cognitive functioning in nondemented people (effect sizes -0.25;0.03), and with brain imaging abnormalities, including atrophy and vascular lesions (ORs 0.94;2.95). Longitudinal studies were more sparse (k = 9) and showed no consistent associations between retinal microvascular changes and dementia or cognitive dysfunctioning 3 to 15 years later (ORs and hazard ratios 0.77;1.55). However, there were indications of prospective associations with brain imaging abnormalities ((ORs) 0.81;3.19). In conclusion, particularly in cross-sectional studies there is a correlation between retinal microvascular changes and dementia, cognitive impairment, and brain imaging abnormalities. Associations are strongest for more severe retinal microvascular abnormalities. Retinal microvascular abnormalities may offer an important window on the brain for etiological studies.

Microvascular Determinants of Cognitive Decline and Brain Volume Change in Elderly Patients with Type 2 Diabetes

Background/Aims: The present study examined the relationship between microvascular complications and cognitive decline and the development of structural brain abnormalities over a period of 4 years in patients with type 2 diabetes mellitus (T2DM). Methods: Sixty-eight elderly patients with T2DM had 2 cognitive assessments with a 4-year interval. Two MRI scans, performed at the same time as the cognitive assessments, were available from 55 patients. Changes in cognitive performance over time were expressed as a regression-based index (RBI). Automated volumetric measurements of total brain, lateral ventricles and white matter hyperintensities were performed. The relationship between baseline microvascular complications [diabetic retinopathy, peripheral neuropathy or albuminuria (micro- or macroalbuminuria)] and cognition and brain volumes was examined with linear regression analyses adjusted for age and sex (for cognition also for IQ). Results: At baseline, diabetic retinopathy was present in 18% of patients, peripheral neuropathy in 36%, albuminuria in 15%. Retinopathy or neuropathy were not significantly associated with baseline cognition or brain volumes, or changes in these measures over time. Albuminuria was associated with a lower composite RBI score, indicating accelerated cognitive decline (adjusted mean difference between patients with or without albuminuria: –0.58, 95% CI –0.85 to –0.31, p < 0.001). Conclusion: Albuminuria predicted accelerated cognitive decline in patients with T2DM, but other microvascular complications were unrelated to accelerated cognitive decline or brain MRI abnormalities.