Downs Syndrome - Dementia Downs Term Paper

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[J-L Gueant2 et. al, (2005)]

Cognitive Functioning and Dementia

2001 study at the university of Guelph, Ontario, Canada has shown that the level of cognitive functioning may have implications for the onset of dementia among downs syndrome patients. The base for the research was the accepted theory that higher education implies greater 'synaptic reserve'. Earlier studies among healthy population has revealed that many years of education have an effect of slowing down the onset of Alzheimer's. Therefore in this study the researchers compared DS patients exhibiting symptoms of dementia and those without such symptoms and correlated them with other factors such as levels of education, recreational activities, employment, etc. In all, 35 adults subjects in the age ranging between 26 and 67 years were included for the study. All the subjects were periodically observed over 3 years and assessed for their decline based on Neuropsychological tests, reports from caregivers, and the Dementia Scale for Down syndrome. Applying the statistical tool of regression analysis, the researchers found that decline was directly related to cognitive functioning and that higher cognitive functioning implied lesser decline. It was also identified from the study that the level of cognitive functioning was by itself related to the other variables such as education, employment and other activities. Since higher cognitive functioning resulted in lesser decline and since cognitive functioning is by itself positively dependent of the environmental variables (education, employment, hobbies, etc.), there is a direct inference that improving cognitive functioning holds the key to preventing the onset of dementia or at least deferring its onset among the Down syndrome population. [Temple, (Feb 2001)]

One recent research looked at the prospect of improving cognitive performance by restoring the communication channels in the hippocampus region, which is primarily responsible for forming, sorting and storing of memories. The researchers used the mouse model Ts65Dn for their study as it replicates very closely the brain model of a downs syndrome patient. Previous research had reported that too much inhibitory signaling maybe the reason for imbalance in the hippocampus communication. (Kleschevnikow et al., 2004). The researches from Stanford University used two behavioral tests (object recognition task and spontaneous alternation task) along with electrophysiological tests on the brain samples from the mouse model to study long-term potentiation (LTP) for exploring the physiological causes behind learning, retention and recalling. The researchers used young Ts65Dn mice along with wild type mouse (WT) as control subjects. Results showed that Ts65Dn subjects exhibited considerable cognitive impairment. Then the researchers administered minor doses of picrotoxin (PTX), bilobalide (BB), and pentylenetetrazol (PTZ) and continued with the experiments. These drugs have a suppressive effect on the inhibitory signals in the hippocampus. To the surprise of the researchers they found that the Ts65Dn mice treated with the drugs performed considerably better in new 'object recognition' and in particular, those mice treated with PTZ, showed improved cognitive performance even when tested 2 months after the withdrawal of the treatment. This latest research result provides new hope of reversing hippocampal communication problems and thus a new pharmacological approach to dementia. [Sietske Heyn, 2007]

Proactive Screening for Dementia

Some studies have focused on the importance and effect of a proactive strategy towards identification and management of dementia in adults with Down's syndrome. Kalsy 2005 is one recent study, which showed that a proactive screening strategy for adults with intellectual disabilities using neuropsychological and behavioral data obtained from clinical assessment could be an effective way to manage dementia. The researchers from the university of Birmingham also outlined psychological interventions for the different stages of dementia. The results based on 18 subjects who were referred to the program showed that a dedicated psychology service and care provision under a multimodal framework is essential for effective management of patients with DS and dementia.

Kalsy (2005)] more recent research focused on developing a valid dementia screening system for adults with downs syndrome. The researchers gathered information from caregivers of a total of 193 DS patients and developed a dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID). The DSQIID was found to have good 'construct validity' and good psychometric properties for screening dementia among Down syndrome patients. [Shoumitro Deb,, (2007)]


Downs syndrome is a debilitating chromosomal disorder that impairs cognitive functions. The disorder is most commonly associated with the other serious condition dementia, and together they severely cripple the patient. Alzheimer's type dementia is the most common one among DS adults. Though several researchers have studied downs syndrome and dementia as co morbid conditions, early diagnosis of dementia in DS patients is largely neglected as symptoms tend to be sidelined as part of downs syndrome. Thus pharmaceutical intervention for dementia in downs syndrome patients is relatively late in most cases. As some studies above have indicated, prevention is better than cure and though controlling dementia may at this time may not be a totally viable idea it is essential that every effort should be focused on delaying the onset of dementia among the DS population. Improving the cognitive functioning by engaging the patient in useful and stimulating activities is one such approach as was mentioned in the research by Temple 2001. Proactive screening for dementia among Down syndrome patients is a suggested solution to the problem of under identified cases of dementia and to facilitate early diagnosis and therapy. Using the DSQIID would be a good way to screen for dementia among the DS population.

We are making new grounds in studying the genetic causes for the disease with the identitification of amyloid precursor protein as the chief cause for the onset of dementia. The discovery of the possible role of the cholesterol transporter ABCG1 and the more recent research on homocysteine metabolism and its effect on the onset of alzheimer's type dementia among Down syndrome patients have shed new light into the genetics of downs syndrome. This new knowledge is indispensible for our future pharmacogentic efforts and is expected to provide a new ray of hope to the DS population. Pharmacological therapy based on the latest research on pentylenetetrazol (PTZ) and picrotoxin (PTX) are also promising with the successful trial on mice model. The fact that these drugs could not only reverse the disrupted hippocampal communication but also sustain it is really an encouraging prospect in the treatment of dementia associated with downs syndrome. In future, with our improved understanding of the genomics of the condition it would be possible to totally cure the disorder but until then providing quality care for the patients is of utmost priority. Periodic screening and an active and involved approach to care giving is necessary to defer the onset of and to minimize the impairment due to dementia associated with DS. A collaborative effort on the part of the physicians representing different neurological specialties, nurses and the care givers is essential for providing quality care for people afflicted with DS and other co morbid conditions.


Lisa R. Stanton and Rikus H. Coetzee (2004), 'Down's syndrome and Dementia', Advances in Psychiatric Treatment (2004) 10: 50-58, Available at,

Tyrrell J, Cosgrave M, McCarron M, Mcpherson J, Calvert J, Kelly a, McLaughlin M, Gill M & Lawlor BA, (Dec 2001), 'Dementia in people with Down's syndrome', Int Journal of geriatric Psychiatry, 16(12): 1168-74

J.D. Pinter, MD; W.E. Brown, BA, S. Eliez, MD; J.E. Schmitt, BS; G.T. Capone, MD; and a.L. Reiss, MD, (2001), 'Amygdala and hippocampal volumes in children with Down syndrome: A high-resolution MRI study', Neurology 2001; 56:972-974

Huxley, Adam; Van-Schaik, Paul; Witts, Paul, (Dec 2005), 'A Comparison of Challenging Behaviour in an Adult Group with Down's Syndrome and Dementia Compared with an Adult Down's Syndrome Group without Dementia', British Journal of Learning Disabilities, v33 n4 p188-193

Deb S, Braganza J, Norton N. et al. Apoliprotein E. e4 allele influences the manifestation of Alzheimer's disease in adults with Down's syndrome. British Journal of Psychiatry 2000; 176: 468-472

Oliver, C. & Adams, D. (2007). The neuropsychological assessment of the early signs of dementia in adults with Down syndrome. Journal of Intellectual Disability Research, 51, 661.

Kalsy, S., McQuillan, S., Adams, D., Lloyd, V., Basra, T., Konstantinidi, E., Broquard, M., Peters S. & Oliver, C. (2005). 'A proactive psychological screening strategy for dementia in adults with Down syndrome: Preliminary description of service use and evaluation' Journal of Policy and Practice in Intellectual Disabilities, 2, 116-125.

Nicole Schupf, PhD,(2002), 'Genetic and host factors for Dementia in Downs syndrome' the British Journal of Psychiatry (2002) 180: 405-410

Stefan J. Teipel, M.D., Mark B. Schapiro, M.D., Gene E. Alexander, Ph.D., Jack S. Krasuski, M.D., Barry Horwitz, Ph.D., Christian Hoehne, Hans-Jurgen Mller, M.D., Stanley I. Rapoport, M.D., and Harald Hampel, M.D, (Oct 2003) 'Relation of Corpus Callosum and Hippocampal Size to Age in Nondemented Adults With Down's Syndrome', Am J. Psychiatry 160:1870-1878

Gavin H. Tansley1,*, Braydon L. Burgess1,*, Matt T. Bryan & Wellington et. al, (May 2007), 'The cholesterol transporter…[continue]

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