Background: As many as 25% of older HIV⁺ adults meet research criteria for dementia (HAD) in the era of HAART. To date, there are no HAD markers specific for this age group. We previously published that diabetes is associated with degree of cognitive impairment among older HIV⁺ adults. In the current study, we theorize that metabolic dysfunction (e.g., insulin resistance) may itself be a risk factor and test the hypothesis that increased insulin resistance is associated with a greater cognitive impairment, independently of diabetes.

Methods:  The Hawaii Aging with HIV Cohort is a longitudinal cohort evaluating cognition and neurological outcomes annually among older (aged  ³50; n = 157) compared with younger (<40; n = 128) HIV⁺ individuals. We measured serum glucose levels on fresh specimens at the time of cognitive testing and later measured serum insulin levels from stored frozen serum drawn at the same time. We then calculated insulin resistance using the homeostasis model of assessment and analyzed the relationship between that and concurrent cognition status, based on consensus determination using American Academy of Neurology criteria:  normal or near normal cognition, minor cognitive motor disorder, and HAD.

Results:  Among the 272 participants enrolled, 166 had fasting specimens on at least 1 annual visit. After excluding patients with substance dependence, a positive urine drug screen, or a history of stroke, data from 74 older and 71 younger patients were analyzed. Among older patients, mean insulin resistance levels were 2.43, 4.69, and 4.90 for normal or near normal cognition, minor cognitive motor disorder, and HAD, respectively (p = 0.013, OR 1.21 [1.04 to 1.40], log reg). The relationship among older patients remained after adding CD4 count, gender, ethnicity, and HAART status (on or off) to the model (p = 0.031). In contrast, among younger patients the levels were 3.45, 3.21, and 2.81, respectively (p = 0.661, log reg). Among all patients (young and old combined) who do not have diabetes (n = 129), homeostasis model of assessment correlated to cognitive diagnosis (p = 0.047).

Conclusions:  We report that insulin resistance (independent of diabetes) may be a novel risk factor for cognitive impairment with particular applicability to older HIV⁺ patients. It is not clear that the neuropathogenesis is specific to HIV, itself; however, common pathways such as oxidative stress may make older patients particularly vulnerable to cognitive sequelae with chronic HIV. Further analyses are underway.