Carotid Intima-Media Thickness as a Predictor of Response to Cholinesterase Inhibitors in Alzheimer's Disease: An Open-Label Trial

Modrego, Pedro J.; Rios, Consuelo; Trullen, José M. Pérez; García-Gómara, Maria J.; Errea, José M.
March 2009
CNS Drugs;2009, Vol. 23 Issue 3, p253
Academic Journal
Background: Cholinesterase inhibitors are modestly effective in treating patients with Alzheimer's disease. However, there may be important inter-individual variations ranging from no improvement at all to significant improvement and long periods of stabilization. Carotid atherosclerosis is associated with cognitive decline in elderly people. Objective: The objective of this study was to investigate whether carotid intima-media thickness (IMT) predicts response to cholinesterase inhibitors in Alzheimer's disease. Patients and methods: A series of 54 patients with mild to moderate Alzheimer's disease were enrolled consecutively in an open-label trial. At baseline, all patients were assessed on the following clinical scales: Mini-Mental State Examination, Clinical Dementia Rating, the Hachinski Ischemic Scale, Blessed Dementia Rating Scale, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Neuropsychiatric Inventory (NPI) and a daily-living activities scale (Disability Assessment for Dementia [DAD]). Investigations included magnetic resonance imaging of the brain and a colour echo-Doppler scan of the carotid arteries to measure the maximum IMT. Patients were then commenced on galantamine treatment for 6 months, after which scores on the ADAS-cog, NPI and DAD scales were reassessed. Results: A total of 50 patients completed the study. Their mean age was 77.78 years (SD 6.51 years); 34 patients were female. Galantamine treatment decreased the mean NPI score from 17.68 to 13.86 points, but this difference was not statistically significant (p = 0.07). On the ADAS-cog scale, a modest and nonsignificant mean difference of -0.4 points (p = 0.7) was observed. A weak (correlation coefficient r = 0.4) but significant correlation between IMT and changes in clinical scale score was found, with low carotid IMT being shown to be a predictor of response on both the ADAS-cog (p = 0.003) and NPI (p = 0.006) scales; these findings were corroborated in multivariate analysis. For men, the correlation was stronger (r = 0.7 and 0.8 for the ADAS-cog and NPI scales, respectively). Conclusion: Although the magnitude of effect was moderate, carotid IMT could be a significant predictor of clinical response to cholinesterase inhibitors in patients with Alzheimer's disease.


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