. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron. 2012 May 10;74(3):467-74. PubMed.


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  1. In my opinion the manuscript is very thought provoking and describes a problem of great interest. However, the literature on this matter is not homogeneous.

    It would be interesting to do a follow-up study of these patients. This issue needs to be more thoroughly investigated, although the cognitive results obtained with levetiracetam (LEV) are indeed very encouraging. The implications of this study are adequately discussed, and the results do support these conclusions, but a univocal interpretation of such positive results is not easy. The section on patients and methods is fairly good, except that there is no comment made about local authority approval or patient consent. There is also no discussion of adverse events. What are the main dosages of LEV utilized in the study? The limitations, namely the small number of patients, and the possibility that they are not adequately matched in a small study like this, are not fully discussed.

    It has been suggested that LEV may influence the brain's metabolism in areas devoted to attention and language, similar to what has been suggested with piracetam, the other pyrrolidone derivative found to be associated with improved learning, memory, and attention. In fact, there is some evidence that piracetam enhances glucose utilization and cellular metabolism in the brain. LEV was initially studied in animal models of cognitive impairment with the primary objective of finding a drug more effective than piracetam. However, LEV was initially considered to be more effective in preventing seizures.

    Our experience of LEV is clinical. We structured a clinical trial to evaluate efficacy, tolerability, and cognitive effects of levetiracetam (LEV) in patients with seizures and Alzheimer’s disease (AD). This was a prospective, randomized, three-arm parallel group, case-control study in 95 patients: LEV (n = 38), phenobarbital (PB) (n = 28), and lamotrigine (LTG) (n = 29). A four-week dose adjustment was followed by a 12-month evaluation period. The three groups were compared to a control group (n = 68) to evaluate cognitive effects. We examined drug effects cross-sectionally at baseline, six, and 12 months. LEV was well tolerated and maintained its efficacy during all long-term management of AD. LEV improved cognitive performance, specifically attention level and oral fluency items. LEV had a benign and neuropsychological side effect profile, making it a cognitively safe drug to use for controlling established seizures in patients with dementia. The mean daily dose of LEV monotherapy was 956 mg (range: 500 to 2,000 mg/day).