. Insulin resistance in cognitive impairment: the InCHIANTI study. Arch Neurol. 2005 Jul;62(7):1067-72. PubMed.

Recommends

Please login to recommend the paper.

Comments

  1. The authors test the association between cognitive impairment (CI) with and without subcortical vascular abnormalities (SF) and insulin resistance (IR) in a cross-sectional population-based study.

    Geroldi et al. subdivided their CI patients between a large group lacking their criteria for the presence of SF (n = 93) and a considerably smaller group with SF (n = 21). These were compared to individuals without CI (n = 381) and individuals who previously experienced stroke, but had no CI (n = 23). The SF classification was based on clinical evaluation and required the presence of at least two of the three determinants: plastic rigidity, small step gait and dysexecutive features. Determination of CI was based on MMSE scores. Individuals who scored 24 or less were classified as CI. Insulin resistance was evaluated by measuring fasting blood insulin, Insulin Resistance Index and Insulin Sensitivity Index.

    The authors found that a higher percentage of CI/SF+ patients were IR compared to CI/SF-. They conclude that insulin resistance contributes to CI only when there is underlying subcortical vascular disease.

    I think that the interpretation of data, especially when derived from cross-sectional studies of a heterologous population of elderly with a number of comorbidities, can be a daunting task. There is a natural bias to arbitrarily create subgroups that would best fit a testable hypothesis, and this manuscript is a perfect example. Upon examination of the raw data, one could easily observe that among the CI elderly with IR, there was probably an equal number of patients with or without SF. More than 70 percent of the CI/SF- group had fasting blood insulin that fell within the 14 +/- 6 μIU/ml values of the CI/SF+ group. The same picture is reflected in the insulin resistance and sensitivity indexes. What is clear, however, from this and other studies, is that a large number of elderly, whether CI or not, have IR and this may exacerbate other pathobiologies in the periphery or CNS. Insulin is a pleiotrophic hormone. The association of IR with a number of neurodegenerative disorders may be attributed to mechanisms that compromise the cerebrovascular walls or regulate glucose utilization. Additionally, there may be disease-specific mechanisms involved (insulin/insulin-degrading enzyme/amyloid link for AD cases).

    Regardless of the etiology of CI, the presence of IR should not be left unattended. What would be of interest, and of great clinical significance, is to determine whether CI patients with IR experience more rapid onset of dementia compared to CI patients who are not IR, and this can be done in longitudinal studies. A carefully designed study will also provide a better understanding of the mechanisms involved and opportunities to address treatment targets.

    In this regard, other metabolic hormones known to affect CNS function and to modulate insulin action (including leptin, somatostatin, and glucagon) may deserve a closer examination.

Make a Comment

To make a comment you must login or register.