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T2DM, poor renal function exert independent, additive effect on risk of cognitive decline

Jairia Dela Cruz
15 Sep 2017

Type 2 diabetes mellitus (T2DM) and impaired renal function are both independently related to abnormal brain structure, as well as poorer cognitive test performance at year 2 following stroke, according to the TABASCO* study.

“Our results demonstrate an additive effect of T2DM and chronic kidney disease (CKD) on cognitive decline because presence of both conditions doubles the risk for poststroke cognitive decline relative to the presence of one [and quadruples the risk when compared with having neither T2DM nor CKD],” the authors said.

In TABASCO, a prospective cohort of stroke/transient ischaemic attack survivors, 507 patients (mean age 67.4 years; 59.4 percent male) underwent cognitive assessments at baseline and at 2 years poststroke. All patients also underwent 3-T magnetic resonance imaging (MRI) at baseline to measure white matter volume and integrity, ischaemic lesions, and brain and hippocampal volumes. [Stroke 2017;48:2368-2374]

MRI data revealed that T2DM and impaired renal function, expressed as estimated creatinine clearance (eCCl) <60 mL/min, were associated with lower brain and hippocampal volumes, decreased cortical thickness, and worse white matter microstructural integrity.

Moreover, cognitive assessment data poststroke showed that both conditions were associated with poorer cognitive scores. Specifically, T2DM was independently related to worse results in memory, executive functions, attention and total cognitive scores; and eCCl <60 mL/min to worse results in memory, visuospatial and total cognitive scores.

A total of 100 patients (19.7 percent) developed cognitive impairment during the 2-year follow-up, among whom 13 had dementia and 87 had mild cognitive impairment.

T2DM (relative hazard ratio [HR], 1.96; 95 percent CI, 1.04 to 3.67; p=0.036) and eCCl <60 mL/min (relative HR, 1.97; 1.01 to 3.83; p=0.046) emerged as significant predictors of cognitive impairment in a multivariate forward stepwise Cox regression model. Other important predictors were older age (≥65 years; relative HR, 3.35; p=0.002) and years of education <12 (relative HR, 1.95; p=0.041).

Patients with both eCCl <60 mL/min and T2DM were twice as likely as those with either condition alone to develop cognitive impairment within 2 years from their index event, and the risk was fourfold higher compared with patients without T2DM and poor renal function (relative HR, 3.8; p=0.004).

In light of the present data and with ageing in the general population, “prevention of cognitive decline becomes a key element for future trials and novel medications,” the authors said.

Furthermore, the impact of recently developed drugs for diabetes mellitus on cognition has not been directly evaluated and does not play a role in current treatment decision algorithms, the authors pointed out.

“Risk prognostication and advanced brain imaging may guide the selection of appropriate therapy to stop or delay vascular cognitive decline in patients with T2DM,” they added.

There are some caveats to interpreting the findings, including the enrolment of only postmild stroke or transient ischaemic attack patients and the inability to take into account other parameters of metabolic control (eg, fasting blood glucose), parameters of insulin resistance and hypoglycaemic events.

*Tel Aviv brain acute stroke cohort

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