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Down Presymptomatic View of Dementia Characteristics

Mohammad Amin Joshaghanian, Sasan Mohammadi, Zohreh Gholizadeh Ghozloujeh, Mehrdad Farahani, Kurosh Mojtabavi




Down syndrome (DS) is caused by complete or segmental chromosome 21 trisomy that results in neurodegeneration and progressive intellectual disability. Abnormal function in the prefrontal cortex, cerebellum, and hippocampus are the main reasons for cognitive deficits in DS that result in impaired cognitive function, delayed speech and language, learning and memory disability, and behavioral and emotional disorders. There is no specific treatment for DS, and our understanding of the mechanisms of the disorder is incomplete and causes to hamper the development of effective therapies regarding the development of neuropathology and memory loss in DS. Here, we review the literature on cognitive functioning, unique characteristics, environmental considerations, and recent findings on Alzheimer’s disease in DS.


Down syndrome (DS); Dementia; Alzheimer’s Disease; Cognitive deficits, Neurodegeneration


Roizen NJ, Patterson D. Down’s syndrome. Lancet. 2003;361(9365):1281-9. doi: 10.1016/s0140-6736(03)12987-x.

Presson AP, Partyka G, Jensen KM, Devine OJ, Rasmussen SA, McCabe LL, et al. Current estimate of Down syndrome population prevalence in the United States. J Pediatr. 2013;163(4):1163-8. doi: 10.1016/j.jpeds.2013.06.013.

Weijerman ME, van Furth AM, Vonk Noordegraaf A, van Wouwe JP, Broers CJ, Gemke RJ. Prevalence, neonatal characteristics, and first-year mortality of Down syndrome: a national study. J Pediatr. 2008;152(1):15-9. doi: 10.1016/j. jpeds.2007.09.045.

Perkins A. The lowdown on Down syndrome. Nursing Made Incredibly Easy. 2017;15(2):40-6. doi: 10.1097/01. NME.0000511841.85763.77

Matthews DC, Lukic AS, Andrews RD, Marendic B, Brewer J, Rissman RA, et al. Dissociation of Down syndrome and Alzheimer’s disease effects with imaging. Alzheimers Dement (N Y). 2016;2(2):69-81. doi: 10.1016/j.trci.2016.02.004.

Pearlson GD, Breiter SN, Aylward EH, Warren AC, Grygorcewicz M, Frangou S, et al. MRI brain changes in subjects with Down syndrome with and without dementia. Dev Med Child Neurol. 1998;40(5):326-34.

Wiseman FK, Al-Janabi T, Hardy J, Karmiloff-Smith A, Nizetic D, Tybulewicz VL, et al. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nat Rev Neurosci. 2015;16(9):564-74. doi: 10.1038/nrn3983.

Cooper SA, Ademola T, Caslake M, Douglas E, Evans J, Greenlaw N, et al. Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study): a pilot randomised controlled trial. Trials. 2016;17:370. doi: 10.1186/s13063-016-1370-9.

Lotfinia M, Lotfinia AA, Khodaie B, Ahmadi M, Asaadi S, Jafarian M. Propagation of spreading depression: a review of different hypothesis. The Neuroscience Journal of Shefaye Khatam. 2014;2(3):53-64. [Persian].

Ball SL, Holland AJ, Treppner P, Watson PC, Huppert FA. Executive dysfunction and its association with personality and behaviour changes in the development of Alzheimer’s disease in adults with Down syndrome and mild to moderate learning disabilities. Br J Clin Psychol. 2008;47(Pt 1):1-29. doi: 10.1348/014466507x230967.

Lott IT, Dierssen M. Cognitive deficits and associated neurological complications in individuals with Down’s syndrome. Lancet Neurol. 2010;9(6):623-33. doi: 10.1016/ s1474-4422(10)70112-5.

Ball SL, Holland AJ, Hon J, Huppert FA, Treppner P, Watson PC. Personality and behaviour changes mark the early stages of Alzheimer’s disease in adults with Down’s syndrome: findings from a prospective population-based study. Int J Geriatr Psychiatry. 2006;21(7):661-73. doi: 10.1002/gps.1545.

Bittles AH, Bower C, Hussain R, Glasson EJ. The four ages of Down syndrome. Eur J Public Health. 2007;17(2):221-5. doi: 10.1093/eurpub/ckl103.

Deb S, Braganza J. Comparison of rating scales for the diagnosis of dementia in adults with Down’s syndrome. J Intellect Disabil Res. 1999;43 (Pt 5):400-7. doi: 10.1046/j.1365- 2788.1999.043005400.x.

Deb S, Hare M, Prior L. Symptoms of dementia among adults with Down’s syndrome: a qualitative study. J Intellect Disabil Res. 2007;51(Pt 9):726-39. doi: 10.1111/j.1365- 2788.2007.00956.x.

Tsao R, Kindelberger C, Fréminville B, Touraine R, Gerald B. Variability of the aging process in dementia-free adults with Down syndrome. Am J Intellect Dev Disabil. 2015;120(1):3- 15. doi: 10.1352/1944-7558-120.1.3.

Holland AJ, Hon J, Huppert FA, Stevens F, Watson P. Population-based study of the prevalence and presentation of dementia in adults with Down’s syndrome. Br J Psychiatry. 1998;172:493-8. doi: 10.1192/bjp.172.6.493.

Tassé MJ, Navas Macho P, Havercamp SM, Benson BA, Allain DC, Manickam K, et al. Psychiatric conditions prevalent among adults with Down syndrome. J Policy Pract Intellect Disabil. 2016;13(2):173-80. doi: 10.1111/jppi.12156.

Vahia VN. Diagnostic and statistical manual of mental disorders 5: a quick glance. Indian J Psychiatry. 2013;55(3):220-3. doi: 10.4103/0019-5545.117131.

Fletcher RJ, Barnhill J, McCarthy J, Strydom A. From DSM to DM-ID. J Ment Health Res Intellect Disabil. 2016;9(3):189- 204. doi: 10.1080/19315864.2016.1185324.

Jaruratanasirikul S, Limpitikul W, Dissaneevate P, Booncharoen P, Tantichantakarun P. Comorbidities in Down syndrome livebirths and health care intervention: an initial experience from the birth defects registry in Southern Thailand. World J Pediatr. 2017;13(2):152-7. doi: 10.1007/s12519-016-0093-z.

McCarron M, McCallion P, Reilly E, Mulryan N. A prospective 14-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Disabil Res. 2014;58(1):61-70. doi: 10.1111/jir.12074.

Alexander M, Petri H, Ding Y, Wandel C, Khwaja O, Foskett N. Morbidity and medication in a large population of individuals with Down syndrome compared to the general population. Dev Med Child Neurol. 2016;58(3):246-54. doi: 10.1111/ dmcn.12868.

Arya R, Kabra M, Gulati S. Epilepsy in children with Down syndrome. Epileptic Disord. 2011;13(1):1-7. doi: 10.1684/ epd.2011.0415.

Lott IT, Doran E, Nguyen VQ, Tournay A, Movsesyan N, Gillen DL. Down syndrome and dementia: seizures and cognitive decline. J Alzheimers Dis. 2012;29(1):177-85. doi: 10.3233/ jad-2012-111613.

Taghdiri MM, Omidbeigi M, Asaadi S, Azargashb E, Ghofrani M. Childhood Epilepsy; Prognostic Factors in Predicting the Treatment Failure. Iran J Child Neurol. 2017;11(1):21-8.

Sobey CG, Judkins CP, Sundararajan V, Phan TG, Drummond GR, Srikanth VK. Risk of Major Cardiovascular Events in People with Down Syndrome. PLoS One. 2015;10(9):e0137093. doi: 10.1371/journal.pone.0137093.

Buss L, Fisher E, Hardy J, Nizetic D, Groet J, Pulford L, et al. Intracerebral haemorrhage in Down syndrome: protected or predisposed? F1000Res. 2016;5. doi: 10.12688/ f1000research.7819.1.

de Sola S, de la Torre R, Sanchez-Benavides G, Benejam B, Cuenca-Royo A, Del Hoyo L, et al. A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials. Front Psychol. 2015;6:708. doi: 10.3389/fpsyg.2015.00708.

Sinai A, Hassiotis A, Rantell K, Strydom A. Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB). PLoS One. 2016;11(5):e0153917. doi: 10.1371/journal.pone.0153917.

Startin CM, Hamburg S, Hithersay R, Davies A, Rodger E, Aggarwal N, et al. The LonDownS adult cognitive assessment to study cognitive abilities and decline in Down syndrome. Wellcome Open Res. 2016;1:11. doi: 10.12688/ wellcomeopenres.9961.1.

Liogier d’Ardhuy X, Edgin JO, Bouis C, de Sola S, Goeldner C, Kishnani P, et al. Assessment of Cognitive Scales to Examine Memory, Executive Function and Language in Individuals with Down Syndrome: Implications of a 6-month Observational Study. Front Behav Neurosci. 2015;9:300. doi: 10.3389/ fnbeh.2015.00300.

Hessl D, Sansone SM, Berry-Kravis E, Riley K, Widaman KF, Abbeduto L, et al. The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions. J Neurodev Disord. 2016;8(1):35. doi: 10.1186/ s11689-016-9167-4.

Walsh DM, Doran E, Silverman W, Tournay A, Movsesyan N, Lott IT. Rapid assessment of cognitive function in down syndrome across intellectual level and dementia status. J Intellect Disabil Res. 2015;59(11):1071-9. doi: 10.1111/ jir.12200.

Gutman M, Moskovic E, Jeret JS. Computerised cognitive testing of individuals with Down’s syndrome and Alzheimer’s disease. J Intellect Disabil Res. 2016;60(2):179-81. doi: 10.1111/jir.12227.

Startin CM, Rodger E, Fodor-Wynne L, Hamburg S, Strydom A. Developing an Informant Questionnaire for Cognitive Abilities in Down Syndrome: The Cognitive Scale for Down Syndrome (CS-DS). PLoS One. 2016;11(5):e0154596. doi: 10.1371/journal.pone.0154596.

Asaadi S, Ashrafi F, Omidbeigi M, Nasiri Z, Pakdaman H, Amini-Harandi A. Persian version of frontal assessment battery: correlations with formal measures of executive functioning and providing normative data for Persian population. Iran J Neurol. 2016;15(1):16-22.

Blok JB, Scheirs JGM, Thijm NS. Personality and behavioural changes do not precede memory problems as possible signs of dementia in ageing people with Down syndrome. Int J Geriatr Psychiatry. 2017;32(12):1257-63. doi: 10.1002/gps.4606.

Sabbagh MN, Chen K, Rogers J, Fleisher AS, Liebsack C, Bandy D, et al. Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer’s dementia. Alzheimers Dement. 2015;11(8):994-1004. doi: 10.1016/j. jalz.2015.01.006.

Jennings D, Seibyl J, Sabbagh M, Lai F, Hopkins W, Bullich S, et al. Age dependence of brain beta-amyloid deposition in Down syndrome: An [18F] florbetaben PET study. Neurology. 2015;84(5):500-7. doi: 10.1212/wnl.0000000000001212.

Lin AL, Powell D, Caban-Holt A, Jicha G, Robertson W, Gold BT, et al. (1)H-MRS metabolites in adults with Down syndrome: Effects of dementia. Neuroimage Clin. 2016;11:728-35. doi: 10.1016/j.nicl.2016.06.001.

Annus T, Wilson LR, Hong YT, Acosta-Cabronero J, Fryer TD, Cardenas-Blanco A, et al. The pattern of amyloid accumulation in the brains of adults with Down syndrome. Alzheimers Dement. 2016;12(5):538-45. doi: 10.1016/j. jalz.2015.07.490.

Salem LC, Sabers A, Kjaer TW, Musaeus C, Nielsen MN, Nielsen AG, et al. Quantitative Electroencephalography as a Diagnostic Tool for Alzheimer’s Dementia in Adults with Down Syndrome. Dement Geriatr Cogn Dis Extra. 2015;5(3):404-13. doi: 10.1159/000438857.

Eady N, Courtenay K, Strydom A. Pharmacological management of behavioral and psychiatric symptoms in older adults with intellectual disability. Drugs Aging. 2015;32(2):95- 102. doi: 10.1007/s40266-014-0236-7.

De la Torre R, De Sola S, Pons M, Duchon A, de Lagran MM, Farre M, et al. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol Nutr Food Res. 2014;58(2):278-88. doi: 10.1002/mnfr.201300325.

Sano M, Aisen PS, Andrews HF, Tsai WY, Lai F, Dalton AJ. Vitamin E in aging persons with Down syndrome: a randomized, placebo-controlled clinical trial. Neurology. 2016;86(22):2071-6. doi: 10.1212/wnl.0000000000002714.


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