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New Markers Predict When Diabetic Patients Develop Cognitive Decline

Stroke and subclinical markers of vascular disease may help predict which older patients with type 2 diabetes will develop cognitive decline….

According to Jackie Price, MD, of the University of Edinburgh, and colleagues, in a large cohort study, having had a stroke was significantly associated with estimated lifetime cognitive decline (P<0.001), and certain subclinical markers of vascular disease were associated with cognitive decline over a 4-year period.

Those markers included N-terminal pro-brain natriuretic peptide (NT-proBNP), ankle-brachial index (ABI), and carotid intima-media thickness (cIMT). The first two were significant at P=0.001 and the third at P<0.001.

"Our results provide additional evidence that the impact of vascular disease on cognition may not be restricted to localized cerebral small vessel disease or altered blood flow and ischemic damage as a consequence of stroke, and that cognitive decline could reflect systemic atherosclerotic changes," they wrote.

"NT-proBNP and cIMT both appear to function as biomarkers of risk of late-life cognitive decline, despite their strong associations with subclinical macrovascular disease in different areas of the vasculature (left ventricle and carotid artery, respectively), and may offer valuable information beyond traditional risk factors," they added.

To assess the relationship between vascular disease and cognitive change in older patients with type 2 diabetes, the researchers conducted the Edinburgh Type 2 Diabetes Study (ET2DS) in 831 patients ages 60 to 75. The researchers recorded cardiovascular event history, cIMT, ABI, and and serum NT-proBNP at baseline, and gave seven neuropsychological tests at baseline and at 4 years.

They looked for effects of vascular disease on both estimated lifetime cognitive change, and late-life cognitive change over a 4-year period. Baseline scores and scores at 4 years were also combined to create a standardized general ability factor. Overall, they found that the general ability factor was significantly lower in those with any cardiovascular event at baseline (P<0.001), particularly for angina (P=0.002) and stroke (P<0.001).

A lower score was also associated with measures of subclinical macrovascular disease, though only the association with higher NT-proBNP reached significance based on Bonferroni estimates (P=0.005).

In multivariate analyses, out of the vascular events, only stroke remained significantly associated with estimated lifetime cognitive change (P<0.001).

In terms of 4-year cognitive decline, however, stroke was only weakly associated, while the markers of subclinical vascular disease were significant predictors. "This pattern of results is of interest because, in terms of identifying elderly subjects at risk for subsequent cognitive decline, information on a patient’s future decline may be more valuable compared with information that incorporates past decline," they wrote.

Only four patients had a diagnosis of dementia after 4 years of follow up. There was a "suggestion" that the prevalence of vascular events was higher in patients with dementia, including transient ischemic attack (P=0.046) and MI (P=0.027), but cautioned that the group was too small for subanalysis.

About two dozen more patients converted to mild cognitive impairment (MCI), and the majority (61%) had some form of cardiovascular disease, which was found to be a significantly higher prevalence compared with the rest of the study population that did not progress to MCI (P=0.039).

Price and colleagues concluded that further studies are needed to determine if these markers could be useful clinical tools in predicting cognitive impairment in patients with type 2 diabetes, and if they can help clinicians target interventions to reduce cognitive decline in this population.

Practice Pearls:

  • Markers assessed included N-terminal probrain natriuretic peptide (NT-proBNP), ankle-brachial index (ABI), and carotid intima-media thickness (cIMT).
  • Stroke and subclinical markers of vascular disease may help predict which older patients with type 2 diabetes will develop cognitive decline.

Diabetes Care Feinkohl I, et al "Clinical and subclinical macrovascular disease as predictors of cognitive decline in older patients with type 2 diabetes" Diabetes Care 2013; DOI: 10.2337/dc12-2241.