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Alzheimer's Disease in Two Populations: A Comparative Study

Patrick J. Fox, Ph.D. and Elizabeth Pohlman, M.A. from the University of California, San Francisco are conducting a research study to understand what it is like to be diagnosed and treated for Alzheimer's disease. They are studying people of old age and people with Down syndrome. Participants will be interviewed with their primary caregivers or guardians. Some individuals may be asked to participate in a longitudinal study, with 4 follow-up visits over a year.

If you have been evaluated for Alzheimer's disease and you have Down syndrome, you are eligible for this study. Primary caregivers or guardians are also included in the study. There is no financial compensation for participation. The study has been approved by the UCSF Committee on Human Research.

For more information, please contact Elizabeth Pohlman at or call (415) 933-6451.

Issue No. 6, Spring 2006

We hope that you like the new rotating image on our home page, featuring people with Down syndrome from our online community. If you would like to share a picture of your daughter or son, we are always glad to enhance our website with more photographs. At this point, we could especially use images of older people with Down syndrome.

As we have had several inquiries about the drug piracetam, we will discuss this substance in relation to therapy in Down syndrome. The drug piracetam is thought to enhance cognitive function in a variety of conditions such as Alzheimer’s disease, dyslexia and stroke. Anecdotal reports suggest that this substance might enhance cognition in Down syndrome, but this claim remains controversial, especially since there is a lack of scientific evidence.

Please contact us if you have questions or comments.



In the spotlight

Piracetam and Down Syndrome
By Sietske Heyn, Ph.D.

In the mid 90ies, media reports, including personal testimonies from parents, publicized the hypothesis that piracetam could improve cognition in children with Down syndrome (1). This publicity, together with advocacy through parent support groups, led to a surge in the administration of this drug to children with Down syndrome. Although anecdotal evidence from parents suggests that piracetam improves cognitive abilities in their children with Down syndrome, there is very little scientific evidence to support this claim.

Piracetam belongs to a class of substances called nootropics that is said to enhance cognitive abilities. It has been available for over thirty years and has been used in attempts to improve cognitive abilities and dysfunction in a variety of conditions, including Alzheimer’s disease (2), developmental dyslexia (3; 4), and stroke (5). Piracetam has also been used in the treatment of vertigo (6), myoclonus (7), and sickle cell anemia (8; 9).

Piracetam is a cyclic derivative of gamma-aminobutric acid (GABA), which plays a key role as a neurotransmitter at inhibitory synapses in the brain. Although piracetam chemically resembles GABA, its mechanism of action appears to be unrelated to the properties of this neurotransmitter (10). The exact mechanism whereby piracetam acts is still not clear, but it influences neuronal and vascular functions (10). On a neuronal level, piracetam modulates neurotransmission in a range of neurotransmitter systems (including cholinergic and glutamatergic), has neuroprotective and anticonvulsant properties, and improves neuroplasticity (Reviewed in 10).

Animal studies (mostly in mice and rats) have demonstrated some improvements in learning and memory while on piracetam (Reviewed in 11). In humans, research results on the efficacy of piracetam as cognitive enhancer have been much more inconsistent and inconclusive. Piracetam has not consistently shown to have beneficial effects in adult-onset cognitive decline (11). In a one-year trial with a high piracetam dose (8 g per day) cognition did not improve in patients with probable Alzheimer’s disease, though it did appear to slow down cognitive decline to some degree (2). Piracetam has also been tested in children with the neurodevelopmental disorder dyslexia. Several studies reported significant benefits on verbal and language-based learning tasks and minimal side effects in dyslexic children, but several other studies reported no benefits at all (Reviewed in 12).

To date, only one systematic study has been reported in the scientific literature that set out to determine whether piracetam therapy might enhance cognition in children with Down syndrome. Eighteen children with Down syndrome (aged 6.5-13 years) completed a randomized, double-blind, placebo-controlled crossover study (1). After their baseline cognitive abilities were assessed, each child was randomly assigned to one of two treatment groups. Treatment consisted of either 4 months on piracetam (80-100 mg/kg per day in 3 doses, 8 hours apart), followed by 4 months on placebo, or 4 months on placebo followed by 4 months on piracetam. After each 4-month treatment phase, a wide range of tests was performed to look for differences in cognitive performance and behavior, while taking piracetam versus placebo. The tests covered many functional domains such as attention, learning and memory, perceptual abilities, executive function, and fine motor and visuomotor skills. In addition, parents and teachers were asked to complete standardized questionnaires at each test phase. The scientists did not find strong evidence to indicate piracetam therapy improved cognition or behavior in children with Down syndrome. They did, however, observe adverse side effects in 7 children. These side effects included aggressiveness or violent behavior (4 children), agitation or irritability (2 children), sexual arousal (2 children), poor sleep (1 child), and decreased appetite (1 child).

Another study was conducted to evaluate the efficacy of piracetam on cognitive performance in a mouse model of Down syndrome to ascertain whether there was a clear preclinical rational for its use in Down syndrome (13). Ts65Dn mice have been used quite extensively as a model for Down syndrome and show many of the characteristic learning and memory deficits observed in children with Down syndrome (14) (See also News & Views issue No. 2). The researchers compared the performance of Ts65Dn mice with their normal littermates in the Morris water maze task - an established model for testing certain types of spatial learning and memory in mice and rats. Normal mice and Ts65Dn mice were tested on a range of piracetam doses (daily injections of either 0, 75, 150, or 300 mg/kg piracetam) for eight weeks. The test phase started after 4 weeks of treatment. While cognitive performance in the water maze improved somewhat for the normal mice during piracetam treatment, Ts65Dn mice showed no improvement. The authors conclude that these experiments do not provide support for the use of piracetam to enhance cognition in Down syndrome.

What conclusion can be drawn from these piracetam studies? Although piracetam has been used as therapy in a variety of conditions over the past thirty years, limited data in children and mouse models show no indication that piracetam is effective in improving cognition in Down syndrome. Anecdotal reports on the efficacy of certain treatment regimens for children should be viewed with caution as side effects may outweigh benefits.



References

Lobaugh, NJ, Karaskov, V, Rombough, V, Rovet, J, Bryson, S, Greenbaum, R, Haslam, RH, and Koren, G (2001) Piracetam therapy does not enhance cognitive functioning in children with Down syndrome. Arch Pediatr Adolsec Med. 155:442-448
Click here to view the abstract and download a free copy of the article

Croisile B, Trillet, M, Fondarai, J, Laurent, B, Mauguière, F, and Billardon, M (1993) Long-term and high-dose piracetam treatment of Alzheimer’s disease. Neurology. 43:301-305

Wilsher, C, Atkins, G, and Manfield, P (1985) Effect of piracetam on dyslexic’s reading ability. J Learn Disab. 18(1):19-25

Ackerman, PT, Dykman, RA, Holloway, C, Paal, NP, and Gocio, MY (1991) A trial of piracetam in two subgroups of students with dyslexia enrolled in summer tutoring. J Learn Disab. 24(9):542-549

Berthier, ML(2005) Poststroke aphasia: epidemiology, pathophysiology and treatment. Drugs Aging. 22(2):163-182

Oosterveld, WJ (1999) The effectiveness of piracetam in vertigo. Pharmacopsychiatry. 32(Suppl 1):54-60

Fedi, M, Reutens, D, Dubeau, F, Andermann, E, D’Agostino, and D, Andermann, F (2001) Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy. Arch Neuol. 58:781-786

El-Hazmi, MA, Warsy, AS, al-Fawaz, I, Opawoye, AO, Taleb, HA, Howsawi, Z, Mohamed, AA, Aly, AW, Refai, S, Sugathan, PS, Rab, AS, Ahmed, HB, Abulaban, M, Abdulkader, AM, and Farid, M (1996) Piracetam is useful in the treatment of children with sickle cell disease. Acta Haematol. 96(4):221-226.

Alvim, RC, Viana, MB, Pires, MAS, Franklin, HMOH, Paula, MJ, Brito, AC, Oliveira, TF, and Rezende, PV (2004) Inefficacy of piracetam in the prevention of painful crises in children and adolescents with sickle cell disease. Acta Haematol. 113:228-233

Winblad, B (2005) Piracetam: A review of pharmacological properties and clinical uses. CNS Drug Rev. 11(2):169-182

Vernon, MW, and Sorkin, EM (1991) Piracetam. An overview of its pharmacological properties and a review of its therapeutic use in senile cognitive disorders. Drugs Aging. 1(1):17-35

Capone, GT (1998) Drugs that increase intelligence?: Application for childhood cognitive impairment. Mental Retard Dev Disab Res Rev. 4:36-49

Moran, TH, Capone, GT, Knipp, S, Davisson, MT, Reeves, RH, and Gearhart, JD (2002) The effects of piracetam on cognitive performance in a mouse model of Down’s syndrome. Physiology & Behavior. 77:403-409
Click here to view the paper’s abstract

Reeves, R.H., Irving, N.G., Moran, T.H., Wohn, A., Kitt, C., Sisodia, S.S., Schmidt, C., Bronson, R.T., and Davisson, M.T. (1995) A mouse model for Down syndrome exhibits learning and behavior deficits. Nature Genetics. 11:177-184

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