Treatment of Alzheimer's Disease

Inkblot: The Undergraduate Journal of Psychology • Vol. 2 • September 2013 | 43 Treatment of Alzheimer’s Disease: A Comparison of Racetam Compounds and Current Medication Jaeger Lam and Bryanna Graves Abstract The purpose of this paper is to examine whether oxiracetam and aniracetam are more effective than donepezil and tacrine, two drugs currently used to treat Alzheimer’s disease. Past research suggests that oxiracetam and aniracetam are more therapeutically efficacious than donepezil and tacrine in the treatment of Alzheimer’s disease symptoms (i.e., cognitive deterioration, tolerability, and quality of life). Oxiracetam and aniracetam appear to reverse the cognitive deficits of Alzheimer’s disease, whereas donepezil and tacrine seem to only slow down the deterioration of cognitive abilities. Research also suggests that oxiracetam and aniracetam may cause improvements in quality of life, whereas donepezil and tacrine provide mild, if any, improvement in quality of life. Future research on Alzheimer’s treatment should be conducted on large populations and focus on direct comparisons of the efficacy between Racetam and non-Racetam compounds. This literature review will discuss the effects of anirace- n.d.). The use of aniracetam and oxiracetam in treating tam and oxiracetam on patients afflicted with Alzheim- Alzheimer’s disease was researched heavily in the 1990s er’s disease. Alzheimer’s disease is an irreversible and (Bottini, Vallar, Cappa, Monza, Scarpini, Baron, & Scar- progressive disease. Symptoms of the disease include lato, 1992; Dager, Loebel, Claypool, Case, Budech, & deterioration in memory, dysfunctional daily living, Dunner, 1992; Davis, Thal, Gamzu, Davis, Woolson, changes in mood and personality, confusion, impaired Gracon, & Doody, 1992; Gouliaev, & Senning, 1994). communication, and loss of bowel and bladder control These studies have shown that the Racetam compounds (National Institutes of Health (NIH), n.d.). decrease symptoms of Alzheimer’s disease. However, Alzheimer’s disease is caused by a combination the research and clinical use of oxiracetam and ani- of genetic and environmental factors (Gatz, 2006). Typ- racetam has come to a standstill for unknown reasons ical onset of Alzheimer’s disease is above the age of 60 (Kenda & Matagne, 2012). years. A definite diagnosis of Alzheimer’s disease can- Past studies have looked into how these drugs not be determined until an autopsy is performed. Due interact with the brain. Oxiracetam and aniracetam to the need for an autopsy to be performed, individu- work in similar ways: oxiracetam stimulates acetylcho- als may be diagnosed with possible Alzheimer’s disease line utilization in the hippocampus and indirectly stim- through questionnaires, memory diagnostics, blood ulates AMPA glutamate receptors (Gouliaev and Sen- tests, urinalyses, and brain imaging. (NIH, n.d.). ning, 1994). Aniracetam, on the other hand, enhances Current approaches to treating Alzheimer’s dis- the efficacy of AMPA-induced calcium influx, increases ease focus on drug therapy (NIH, n.d.). The purpose of acetylcholine content in the hippocampus and cerebral using drugs is to slow down or delay the onset of symp- cortex, and decreases the dopamine level in the stria- toms in those afflicted with Alzheimer’s disease (NIH, tum and the hypothalamus. An important characteris- 44 | Inkblot: The Undergraduate Journal of Psychology • Vol. 2 • September 2013 tic of these Racetam compounds relates to their effect ness of Bottini et al.’s (1992) study was its small sample on acetylcholine in the hippocampus. Acetylcholine size of 65 participants. Nonetheless, a study by Maina, in the hippocampus has been associated with learning Fiori, Torta, Fagiani, Ravizza, Bonavita, and Macciolli activation and memory; animal models with induced (2008), found similar results using a larger sample size memory impairments have found behavioral deficits in of 289 participants. In particular, the oxiracetam group learning, as well as a decrease in hippocampal acetyl- showed significant improvement on the Blessed De- choline (Roland, 2003). mentia Scale (BDS); the BDS contains scales that mea- Currently, relatively newer and more popular sure information, memory, and concentration abilities, medications, such as donepezil and tacrine, have been all of which are indicators of cognitive improvement. discovered and are now first-line treatments for Al- In a study by Villardita, Grioli, Lomeo and Cattaneo’s zheimer’s disease. Whether these new medications are (1992), similar results in cognitive improvement were more effective than Racetam compounds is an issue that found, where cognitive ability was operationalized as must be addressed. This literature review will explore memory retention, and was tested using word recall and Racetam research that is focused on certain aspects of word recognition. the disease (cognitive ability, and quality of life), includ- Other studies, however, have brought the effica- ing a comparison between Racetam containing drugs cy of oxiracetam on cognitive ability into question. For and recent medications, in terms of their therapeutic example, a study by Green, Goldstein, Auchus, Presley, efficacy. Clark, Van Tuyl, and Karp (1992) found no therapeutic efficacy of the oxiracetam treatment on Alzheimer’s The Racetam Compounds disease. This study, however, had a number of flaws: a small sample size of 24 participants; withdrawal of par- Oxiracetam ticipant results; plausible bias (funded by GSK pharma- Oxiracetam, like other Racetam compounds, is ceuticals); and premature termination after one month, not currently prescribed as a treatment for Alzheimer’s instead of the planned three months. Despite its short- disease. However, studies suggest that oxiracetam has comings, the study concluded that oxiracetam did not the ability to slow down, or completely halt, the dis- offer meaningful clinical improvement in cognitive ease’s progression. There are a number of studies that functioning. It is important to note that studies where have shown an improvement in patients’ symptoms researchers found significant positive results were per- pertaining to cognitive ability. In a double-blind, be- formed over a minimum period of 12 weeks (Bottini tween-patient study conducted by Bottini et al. (1992), et al. 1992; Maina, et al., 1989; Villardita et al., 1992). the administration of 1600 mg/day of oxiracetam was Thus, the research suggests that oxiracetam requires at observed to significantly improve phonemic memory, least 12 weeks to demonstrate observable positive ef- semantic memory, short-term memory recall, and rec- fects on participants afflicted with Alzheimer’s disease. ognition in Alzheimer’s disease patients. In contrast, a After a thorough review of the oxiracetam literature, steady deterioration in cognitive ability, according to only one methodologically imperfect study was found results found from the same group of neuropsychologi- (see Green et al., 1992). Evidence found in the major- cal tests, was observed in the placebo condition. Most ity of articles suggests that oxiracetam may be effective noteworthy were the results of the semantic memory in improving the cognitive functioning of participants tests (including short story recall, semantic tasks, digit with Alzheimer’s disease (Bottini, et al., 1992; Dager, et span tests, and word list tests), which showed significant al., 1992; Maina, et al., 1989). improvements in the oxiracetam group. A major weak- Quality of life was another factor that was seen Inkblot: The Undergraduate Journal of Psychology • Vol. 2 • September 2013 | 45 to be improved by the use of oxiracetam. Villardita, et ability concerns (Bottini, et al., 1992; Dager, et al., 1992; al., (1992) found improved quality of life (as measured Maina, et al., 1989; Villardita, Grioli, Lomeo, Cattane, by the non-self-report Luria Alternating Series and In- & Parini, 2008). As discussed, however, the available strumental Activities of Daily Living) in a portion of research is limited. Additionally, since the elderly are their participants medicated with oxiracetam, though often prescribed medication unrelated to Alzheimer’s these improvements were not entirely consistent after disease, further research needs to be conducted involv- 12 months of usage. Bottini et al. (1992) also found im- ing drug interactions. proved quality of life in the oxiracetam group, as measured by the Italian Quality of Life Scale (IQLS), over Aniracetam the course of 12 weeks, when compared to a placebo There have been a small number of studies group. A study by Maina et al. (1989) made similar con- conducted on the use of aniracetam in the treatment clusions based on the Psychic and Somatic Complaints of Alzheimer’s disease. One such study was a double- in the Elderly (IPSC-E) questionnaire. A case study by blind placebo study conducted by Senin, Abate, Fies- Dager et al. (1992) found that, at an individual level, pa- chi & Gori (1991). In this particular study, researchers tients who were treated with oxiracetam were reported looked at the Rey-15 word test as a measure of memory as being more sociable, performing better in functions feigning, the Corsi test as an assessment of visuo-spatial of daily living, and having a higher positive affect and short term working memory, and the Raven colored level of independent functioning. Upon patients’ dis- progressive matrices as a measure of abstract reason- continuation of the medication, a progressive decline in ing. Some other factors examined in

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