According to the Center for Disease Control and Prevention (CDC) Down syndrome (DS) is a condition in which a person has an extra chromosome. Babies, normally, born with 46 chromosomes but those with down syndrome have an extra copy of the chromosome 21. The medical term for this kind of situation is ‘trisomy’. This trisomy affects how the babies’ body and brains develop. There are another two different causes of DS, in the 4 % of the cases a full or partial copy of the chromosome 21 attaches to another chromosome, which is called ‘translocation’. And the other cause, with a very small percentage of cases are due to a mixture of normal cells with two copies of the chromosome 21 and other cells that suffer a trisomy.
There are many studies which show that at older ages in the case of the mother, the prevalence of DS increases.1,2 The highest frequency of DS cases is found in the groups of parents with an age between 30-39 years.2However, due to higher birth rates in younger women, around the 80% of children with DS are related to women under 35 years.3
The incidence of cognitive decline and dementia is very high in the case of the people with DS. This dementia is thought to be linked with the extra genes present in the people with DS, due to the relation of the chromosome 21 with the amyloid protein precursor (APP), also important in the Alzheimer’s disease (AD). In the amyloid cascade hypothesis of Hardy and Higgins4, the accumulation of amyloid-beta peptide (Aβ), derived from the APP cleavage by the beta secretase and gamma secretase, is the primary cause of AD. The first response is an inflammatory response followed by neuritic injury, hyperphosphorylation of tau protein, and formation of neurofibrillary tangles, leading to cell death and neuronal dysfunction.5,6
1Mai, C. T., Kucik, J. E., Isenburg, J., Feldkamp, M. L., Marengo, L. K., Bugenske, E. M., … for the National Birth Defects Prevention Network. (2013). Selected birth defects data from population-based birth defects surveillance programs in the United States, 2006 to 2010: Featuring trisomy conditions: U.S. Trisomy Conditions: 2006-2010. Birth Defects Research. Part A, Clinical and Molecular Teratology, 97(11), 709–725.
2Sotonica, M., MackicDjurovic, M., Hasic, S., Kiseljakovic, E., Jadric, R., &Ibrulj, A. (2016). Association of parental age and the type of down syndrome on the territory of Bosnia and Herzegovina. Medical archives (Sarajevo, Bosnia and Herzegovina), 70(2), 88.
3Olsen, C. L., Cross, P. K., Gensburg, L. J., & Hughes, J. P. (1996). The effects of prenatal diagnosis, population ageing, and changing fertility rates on the live birth prevalence of Down syndrome in New York State, 1983-1992. Prenatal Diagnosis, 16(11), 991–1002.
4Hardy, J. A., & Higgins, G. A. (1992). Alzheimer’s disease: the amyloid cascade hypothesis. Science (New York, N.Y.), 256(5054), 184–185.
5Bakkar, R. M., Luo, G., Webb, T. A., Crutcher, K. A., & de Courten-Myers, G. M. (2010). Down’s syndrome with Alzheimer’s disease-like pathology: What can it teach us about the amyloid cascade hypothesis? International JournalofAlzheimer’sDisease, 2010, 1–7.
6Schweber M. S. (1989). Alzheimer’s disease and Down syndrome. Progress in clinical and biological research, 317, 247–267.
Tosh, J. L., Rhymes, E. R., Mumford, P., Whittaker, H. T., Pulford, L. J., Noy, S. J., … Wiseman, F. K. (2021). Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models. Scientific Reports, 11(1), 5736.
Lott, I. T., & Head, E. (2019). Dementia in Down syndrome: unique insights for Alzheimer disease research. Nature Reviews. Neurology, 15(3), 135–147.
Wiseman, F. K., Al-Janabi, T., Hardy, J., Karmiloff-Smith, A., Nizetic, D., Tybulewicz, V. L. J., … Strydom, A. (2015). A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nature Reviews. Neuroscience, 16(9), 564–574.
Shi, Y., Kirwan, P., Smith, J., MacLean, G., Orkin, S. H., & Livesey, F. J. (2012). A human stem cell model of early Alzheimer’s disease pathology in Down syndrome. Science Translational Medicine, 4(124), 124ra29.
Ness, S., Rafii, M., Aisen, P., Krams, M., Silverman, W., & Manji, H. (2012). Down’s syndrome and Alzheimer’s disease: towards secondary prevention. Nature Reviews. Drug Discovery, 11(9), 655–656.
Wiseman, F. K. (2009). Cognitive enhancement therapy for a model of Down syndrome. Science Translational Medicine, 1(7), 7ps9.
Salehi, A., Faizi, M., Colas, D., Valletta, J., Laguna, J., Takimoto-Kimura, R., … Mobley, W. C. (2009). Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome. ScienceTranslational Medicine, 1(7), 7ra17.
Hardy, J., &Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science (New York, N.Y.), 297(5580), 353–356.
Reeves, R. H., Irving, N. G., Moran, T. H., Wohn, A., Kitt, C., Sisodia, S. S., … Davisson, M. T. (1995). A mouse model for Down syndrome exhibits learning and behaviour deficits. Nature Genetics, 11(2), 177–184.
Kolata, G. (1985). Down syndrome–Alzheimer’s linked. Science (New York, N.Y.), 230(4730), 1152–1153.
Mann, D. M. (1983). The locus coeruleus and its possible role in ageing and degenerative disease of the human central nervous system. MechanismsofAgeing and Development, 23(1), 73–94.
- Down Syndrome Research Foundation
- Down Syndrome Research Center
- Down Syndrome Clinic and Research Center – Kennedy Krieger Institute
- Down Syndrome Consortium – Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Down Syndrome Center – Emory University School of medicine
- Down Syndrome Research Program – Massachusetts General Hospital
The results obtained for the gender-related differences in the prevalence of the dementia in persons with Down syndrome are contradictory.1,2 On one hand, there are some studies where seems that there is not a significant difference in the risk of develop dementia between men and women3, but on the other hand, some studies have reached to the conclusion that women were at increased risk of earlier onset of the disease.5
Taking into account the information available nowadays, is not possible to conclude that the gender is a risk factor in the developing of dementia in the people with DS or in the earlier onset of the disease.
1Lai, F., Kammann, E., Rebeck, G. W., Anderson, A., Chen, Y., & Nixon, R. A. (1999). APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome. Neurology, 53(2), 331–336.
2Schupf, N., Kapell, D., Nightingale, B., Rodriguez, A., Tycko, B., & Mayeux, R. (1998). Earlier onset of Alzheimer’s disease in men with Down syndrome. Neurology, 50(4), 991–995.
3Lai, F., Mhatre, P. G., Yang, Y., Wang, M.-C., Schupf, N., & Rosas, H. D. (2020). Sex differences in risk of Alzheimer’s disease in adults with Down syndrome. Alzheimer’s&Dementia (Amsterdam, Netherlands), 12(1), e12084.
5Seltzer, G. B., Schupf, N., & Wu, H. S. (2001). A prospective study of menopause in women with Down’s syndrome. JournalofIntellectualDisabilityResearch: JIDR, 45(Pt 1), 1–7.
- There are three types of DS:
- Trisomy 21 – 95% cases
- Translocation – 4% cases
- Mosaicism – 1% cases
- DS is the most commonly occurring chromosomal disorder
- It can occur in all the races and economic levels
- The age of the mother is the main risk, showing a high incidence of DS at older ages
- In disease as AD, childhood leukemia, thyroid conditions, congenital heart defects and respiratory and heard problems, DS is a risk factor.
- In 1983 the life expectancy for people with DS was 25 and nowadays, that life expectancy has increased to 60 years of age.
- By age 40, most people with DS have a higher risk of developing AD.
*National Down Syndrome Society and the National Insitute on Aging webpages.