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© 2002 by the American Diabetes Association, Inc.
Letters: Observations |
Atorvastatin, Diabetic Dyslipidemia, and Cognitive Functioning
1 Department of Internal Medicine, University Hospital Rotterdam, The Netherlands
2 Department of Neurology, University Hospital Rotterdam, The Netherlands
3 Julius Center for Patient Oriented Research, Utrecht, The Netherlands
4 Department of Anthropogenetics, University Medical Center Nijmegen, The Netherlands
Cognitive functioning is reduced in patients with type 2 diabetes as compared with age-matched patients without diabetes (1). In particular, verbal memory and complex information processing are affected in patients with diabetes, which has an impact on daily functioning (2). The severity of cognitive dysfunction in patients with diabetes presumably results from an interaction between risk factors for macro- and microvascular disease (3). Previous studies suggest a positive association between indexes of cognitive impairment and elevation of plasma triglyceride level (4,5). The effect of lowering serum triglyceride levels by gemfibrozil on cognitive functioning has been investigated in elderly hypertriglyceridemic patients (11 of the 44 patients had diabetes). Lowering triglyceride levels appeared beneficial to cerebral perfusion and cognitive performance after 4–6 months (6). Therefore, we studied in the Diabetes Atorvastatin Lipid Intervention (DALI) study (7), the effect of atorvastatin on diabetic dyslipidemia and cognitive functioning. Thirty patients with diabetes, aged 45–75 years, with fasting triglycerides between 1.5 and 6.0 mmol/l and total cholesterol levels between 4.0 and 8.0 mmol/l, and without ischemic heart and cerebrovascular disease were included. Patients received placebo (n = 8), 10 mg atorvastatin (n = 7), or 80 mg atorvastatin (n = 11) during 30 weeks. Two patients withdrew before the end of the study for personal reasons, and two patients withdrew because of protocol violation. Fasting lipids and neuropsychological tests were assessed at baseline and after 30 weeks. The neuropsychological test-battery was composed in line with the findings of previous studies with comparable groups (1). Orientation and auditory-verbal memory were tested, as well as attention, psychomotor speed, and executive functioning. Furthermore, we estimated premorbid intelligence with the Dutch version of the National Adult Reading Test (NLV). Baseline characteristics, lipids, and neuropsychological tests results did not differ between the intervention groups. The mean HbA1c was 8.1 ± 1.0%, and the diabetes duration was 8.9 ± 5.9 years. Atorvastatin 10 and 80 mg respectively reduced plasma triglyceride by 19 and 39%, total cholesterol by 27 and 42%, and LDL cholesterol by 36 and 56%. The baseline results of the auditory-verbal memory test were below mean (i.e., 
1 SD) in 71% of the study population, in comparison with the normative data (8). The baseline results on the other neuropsychological tests did not differ from a nondiabetic population. The verbal memory test (CVLT) improved 24% (a mean of seven extra words) after 30 weeks of treatment with atorvastatin 80 mg. In the atorvastatin 10 mg group, the CVLT improved only 8% (a mean of two extra words), and in the placebo group, no effect was observed. Verbal memory improvement correlated with an increase in HDL cholesterol (r = 0.67, P < 0.05), a reduction in LDL cholesterol (r = -0.34, P < 0.05), and a reduction in triglycerides (r = -0.34, P = 0.07) after adjustment for age, baseline HDL cholesterol, LDL cholseterol, triglycerides, and verbal memory in the entire population. Atorvastatin did not affect psychomotor speed, attention, and executive functioning.
To summarize, in this small cohort of hyperlipidemic patients with type 2 diabetes who were treated with atorvastatin, verbal memory improvement was associated with improvement of the diabetic dyslipidemia profile. Low- and high-dose atorvastatin had no significant effect on cognitive functioning.
Footnotes
Address correspondence to Ingrid Berk-Planken, Department of Internal Medicine, University Hospital Dijkzigt, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: Berk{at}inw3.azr.nl.
References
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Dornan TL, Peck GM, Dow JDC, Tattersall RB: A community survey of diabetes in the elderly. Diabet Med 9:860–865, 1992[Medline]
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Ryan CM, Geckle M: Why is learning and memory dysfunction in type 2 diabetes limited to older adults? Diabete Metab Res Rev 16:308–315, 2000
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Perlmuter LC, Nathan DM, Goldfinger SH, Russo PA, Yates J, Larkin M: Triglyceride levels affect cognitive function in noninsulin-dependent diabetics. J Diabetic Complications 2:210–213, 1988[Medline]
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Helkala EL, Niskanen L, Vinamaki h, Partanen J, Uusitupa M: Short-term and long-term memory in elderly patients with NIDDM. Diabetes Care 18:681–685, 1995[Abstract]
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Rogers RL, Meyer JS, McClintic K, Mortel KF: Reducing hypertriglyceridemia in elderly patients with cerebrovascular disease stabilizes or improves cognition and cerebral perfusion. Angiology 40:260–269, 1989
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The DALI Study Group: The effect of aggressive versus standard lipid lowering by atorvastatin on diabetic dyslipidemia. Diabetes Care 24:1335–1341, 2001
[Abstract/Free Full Text]
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Mulder JL, Dekker R, Dekker PH: Verbale Leer en geheugen Test Handleiding (Dutch manual). Lisse, Swets and Zeitlinger, 1996
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