What is a case study that illustrates typical Alzheimer disease (AD) in Down syndrome (DS) progression?

Answer

A male born in 1930 was admitted to an institution for individuals with mental retardation in 1939. He died in the institution in 1991, and diagnosis of DS was confirmed by chromosomal analysis. The following is the author's account of disease evolution in this individual, who was observed from disease onset, and demonstrates the complexity of the medical issues involved.

Clinical presentation before the beginning of AD was as follows:

Patient had no behavioral problems and was pleasant and congenial
Patient followed simple commands and understood simple orders
Patient walked independently and also was independent in ADLs
Patient consumed a normal diet
Patient performed housework and showered well
Patient had good leisure skills and an active social program, participated in dances and outdoor trips, and sang with the radio
Patient understood that he had to leave the building when a fire alarm sounded
Patient's score on the Vineland Adaptive Behavior Scale in 1975, at the age of 45 years, was 4.9 years; this remained the same when he was aged 49 years

The following is a yearly description of the patient’s symptoms as he developed AD:

1981 (51 y) - The patient's first symptoms were disorientation, confusion, and behavior changes; he refused to accept that the program activity in which he was involved was over; he refused to return to his residence; he was found wandering the grounds crying and yelling in a state of confusion
1982 (52 y) - The patient showed increased forgetfulness and had emotional problems and periods of agitation manifested by verbal outbursts and throwing of objects
1983 (53 y) - The patient needed consistent prompting to perform ADLs; he was still capable of showering and changing clothes daily; leisure skills were unchanged; he exhibited 3 incidents of major aggression and agitation; his score on the Vineland Adaptive Behavior Scale decreased to 3 years
1984 (54 y) - The patient demonstrated poor participation in social activities as a consequence of frequent sleeping; ADLs required increased assistance, although he remained independent; a choking episode was observed
1985 (55 y) - Regression steadily continued; disorientation, confusion, wandering, forgetfulness, and sleeping increased; the patient's behavior deteriorated; he would undress in the dining room and at work; ADLs also regressed, and he needed more help though remaining independent; he frequently was found wandering outside his residence and unable to find his way; occasionally, he could not find his bedroom; the score on the Vineland Adaptive Behavior Scale decreased to 2.1 years
1986 (56 y) - The patient exhibited photomyoclonic response; he had myoclonic seizures and difficulty walking; ADLs regressed further; he still could eat and drink but had to be reminded constantly to do so; he was transferred to a safer and more restrictive environment
1987 (57 y) - Generalized tonic-clonic seizures appeared; the patient became aggressive, and his gait deteriorated markedly, though he was still able to walk; he occasionally needed a wheelchair; he fed himself using adaptive equipment; toilet training was scheduled, but a few accidents occurred
1988 (58 y) - The patient became lethargic; inappropriate behavior became frequent; he no longer was able to walk independently or feed himself; he frequently lost sphincter control; he could not tolerate bus rides into the community; he still enjoyed music and expressed pleasure by smiling and laughing
1989 (59 y) - The patient developed aspiration pneumonia; he was totally dependent for ADLs; he required a wheelchair, and his social interaction became very poor; he developed urinary incontinence
1990 (60 y) - The patient suffered from frequent bouts of pneumonia; he no longer was able to swallow and was fed through a naso gastric tube; a feeding tube (percutaneous endoscopic gastronomy) was placed; incontinence necessitated the use of diapers; he had minimal interaction with his surroundings and slept most of the time; occasionally, he conveyed pleasure and displeasure by laughing or crying
1991 (61 y) - The patient showed minimal response to environmental stimulation and slept most of the time

Did this answer your question?

Yes No

Additional feedback? (Optional)

Thank you for your feedback!

What is dementia?. Alzheimer's Association. Available at http://www.alz.org/alzheimers_disease_what_is_dementia.asp. Accessed: February 2012.
Heyman A, Wilkinson WE, Stafford JA, Helms MJ, Sigmon AH, Weinberg T. Alzheimer's disease: a study of epidemiological aspects. Ann Neurol. 1984 Apr. 15(4):335-41. [Medline].
Zigman WB, Devenny DA, Krinsky-McHale SJ, Jenkins EC, Urv TK, Wegiel J, et al. Alzheimer's Disease in Adults with Down Syndrome. Int Rev Res Ment Retard. 2008 Jan 1. 36:103-145. [Medline].
Fraser J, Mitchell A. Kalmuc idiocy: report of a case with autopsy with notes on sixty two cases. J Ment Sci. 1876. 22:169–79.
Zigman WB, Lott IT. Alzheimer's disease in Down syndrome: neurobiology and risk. Ment Retard Dev Disabil Res Rev. 2007. 13(3):237-46. [Medline].
Small DH, Cappai R. Alois Alzheimer and Alzheimer's disease: a centennial perspective. J Neurochem. 2006 Nov. 99(3):708-10. [Medline].
Cutler NR, Heston LL, Davies P, Haxby JV, Schapiro MB. NIH Conference. Alzheimer's disease and Down's syndrome: new insights. Ann Intern Med. 1985 Oct. 103(4):566-78. [Medline].
Allsop D, Landon M, Kidd M, Lowe JS, Reynolds GP, Gardner A. Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease. Neurosci Lett. 1986 Jul 24. 68(2):252-6. [Medline].
Glenner GG, Wong CW. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984 Aug 16. 122(3):1131-5. [Medline].
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun. 82(12):4245-9. [Medline]. [Full Text].
Becker L, Mito T, Takashima S, Onodera K. Growth and development of the brain in Down syndrome. Prog Clin Biol Res. 1991. 373:133-52. [Medline].
Mann DM, Yates PO, Marcyniuk B. Alzheimer's presenile dementia, senile dementia of Alzheimer type and Down's syndrome in middle age form an age related continuum of pathological changes. Neuropathol Appl Neurobiol. 1984 May-Jun. 10(3):185-207. [Medline].
Wisniewski KE, Dalton AJ, McLachlan C, Wen GY, Wisniewski HM. Alzheimer's disease in Down's syndrome: clinicopathologic studies. Neurology. Jul 1985. 35(7):957-61.
Lai F. Clinicopathological features of Alzheimer's disease in Down's syndrome. Down's Syndrome and Alzheimer's Disease. New York: Wiley-Liss Inc; 1992. 15-34.
Burt DB, Loveland KA, Primeaux-Hart S, Chen YW, Phillips NB, Cleveland LA, et al. Dementia in adults with Down syndrome: diagnostic challenges. Am J Ment Retard. 1998 Sep. 103(2):130-45. [Medline].
Visser FE, Aldenkamp AP, van Huffelen AC, Kuilman M, Overweg J, van Wijk J. Prospective study of the prevalence of Alzheimer-type dementia in institutionalized individuals with Down syndrome. Am J Ment Retard. 1997 Jan. 101(4):400-12. [Medline].
Zigman WB, Schupf N, Sersen E, Silverman W. Prevalence of dementia in adults with and without Down syndrome. Am J Ment Retard. 1996 Jan. 100(4):403-12. [Medline].
Carr J. Six weeks to 45 years: a longitudinal study of a population with Down syndrome. J Appl Res Intellect Disabil. 2012 Sep. 25(5):414-22. [Medline].
Cooper SA, Prasher VP. Maladaptive behaviours and symptoms of dementia in adults with Down's syndrome compared with adults with intellectual disability of other aetiologies. J Intellect Disabil Res. 1998 Aug. 42 ( Pt 4):293-300. [Medline].
Cosgrave MP, Tyrrell J, McCarron M, Gill M, Lawlor BA. Determinants of aggression, and adaptive and maladaptive behaviour in older people with Down's syndrome with and without dementia. J Intellect Disabil Res. 1999 Oct. 43 ( Pt 5):393-9. [Medline].
Holland AJ, Hon J, Huppert FA, Stevens F. Incidence and course of dementia in people with Down's syndrome: findings from a population-based study. J Intellect Disabil Res. 2000 Apr. 44 ( Pt 2):138-46. [Medline].
Temple V, Konstantareas MM. A comparison of the behavioural and emotional characteristics of Alzheimer's dementia in individuals with and without Down syndrome. Can J Aging. 2005 Summer. 24(2):179-89. [Medline].
Blacker D, Tanzi RE. The genetics of Alzheimer disease: current status and future prospects. Arch Neurol. 1998 Mar. 55(3):294-6. [Medline].
Olson LE, Roper RJ, Sengstaken CL, Peterson EA, Aquino V, Galdzicki Z, et al. Trisomy for the Down syndrome 'critical region' is necessary but not sufficient for brain phenotypes of trisomic mice. Hum Mol Genet. 2007 Apr 1. 16 (7):774-82. [Medline].
Griffiths-Jones S. The microRNA Registry. Nucleic Acids Res. 2004 Jan 1. 32 (Database issue):D109-11. [Medline].
Vilardell M, Rasche A, Thormann A, Maschke-Dutz E, Pérez-Jurado LA, Lehrach H, et al. Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes. BMC Genomics. 2011 May 11. 12:229. [Medline].
Zana M, Janka Z, Kálmán J. Oxidative stress: a bridge between Down's syndrome and Alzheimer's disease. Neurobiol Aging. 2007 May. 28(5):648-76. [Medline].
Schupf N, Kapell D, Nightingale B, Lee JH, Mohlenhoff J, Bewley S, et al. Specificity of the fivefold increase in AD in mothers of adults with Down syndrome. Neurology. 2001 Sep 25. 57 (6):979-84. [Medline].
Schupf N, Sergievsky GH. Genetic and host factors for dementia in Down's syndrome. Br J Psychiatry. 2002 May. 180:405-10. [Medline].
Schupf N, Winsten S, Patel B, Pang D, Ferin M, Zigman WB, et al. Bioavailable estradiol and age at onset of Alzheimer's disease in postmenopausal women with Down syndrome. Neurosci Lett. 2006 Oct 9. 406 (3):298-302. [Medline].
Hooli BV, Mohapatra G, Mattheisen M, Parrado AR, Roehr JT, Shen Y, et al. Role of common and rare APP DNA sequence variants in Alzheimer disease. Neurology. 2012 Apr 17. 78 (16):1250-7. [Medline].
McNaughton D, Knight W, Guerreiro R, Ryan N, Lowe J, Poulter M, et al. Duplication of amyloid precursor protein (APP), but not prion protein (PRNP) gene is a significant cause of early onset dementia in a large UK series. Neurobiol Aging. 2012 Feb. 33 (2):426.e13-21. [Medline].
Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerrière A, Vital A, et al. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet. 2006 Jan. 38 (1):24-6. [Medline].
Teller JK, Russo C, DeBusk LM, Angelini G, Zaccheo D, Dagna-Bricarelli F, et al. Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down's syndrome. Nat Med. 1996 Jan. 2 (1):93-5. [Medline].
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 Sep. 16 (9):564-74. [Medline].
Sun X, Tong Y, Qing H, Chen CH, Song W. Increased BACE1 maturation contributes to the pathogenesis of Alzheimer's disease in Down syndrome. FASEB J. Jul 2006. 20(9):1361-8.
Shi J, Zhang T, Zhou C, Chohan MO, Gu X, Wegiel J, et al. Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome. J Biol Chem. 2008 Oct 17. 283 (42):28660-9. [Medline].
Zigman WB, Schupf N, Jenkins EC, Urv TK, Tycko B, Silverman W. Cholesterol level, statin use and Alzheimer's disease in adults with Down syndrome. Neurosci Lett. 2007 Apr 18. 416 (3):279-84. [Medline].
Cooper SA, Caslake M, Evans J, Hassiotis A, Jahoda A, McConnachie A, et al. Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study): study protocol for a randomized controlled trial. Trials. 2014 Jun 3. 15:202. [Medline].
Schupf N, Sergievsky GH. Genetic and host factors for dementia in Down's syndrome. Br J Psychiatry. 2002 May. 180:405-10. [Medline].
Alzheimer's Association. ApoE genotyping. Available at http://www.alz.org. Accessed: 2006.
Alzheimer's Association. Genes and alzheimer's disease. Available at http://www.alz.org. Accessed: 2006.
Bush A, Beail N. Risk factors for dementia in people with down syndrome: issues in assessment and diagnosis. Am J Ment Retard. 2004 Mar. 109(2):83-97. [Medline].
Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DL. Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. Am J Med Genet A. 2011 Aug. 155A (8):1939-48. [Medline].
Lee HG, Zhu X et al. Amyloid beta: the alternate theory. Current Alzheimer Research. 2006. 3:75-80.
Beacher F, Simmons A, Daly E, Prasher V, Adams C, Margallo-Lana ML, et al. Hippocampal myo-inositol and cognitive ability in adults with Down syndrome: an in vivo proton magnetic resonance spectroscopy study. Arch Gen Psychiatry. 2005 Dec. 62(12):1360-5. [Medline].
Teipel SJ, Hampel H. Neuroanatomy of Down syndrome in vivo: a model of preclinical Alzheimer's disease. Behav Genet. 2006 May. 36(3):405-15. [Medline].
Takashima S, Iida K, Mito T, Arima M. Dendritic and histochemical development and ageing in patients with Down's syndrome. J Intellect Disabil Res. 1994 Jun. 38 ( Pt 3):265-73. [Medline].
Stern Y. Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol. 2012 Nov. 11 (11):1006-12. [Medline].
Zigman WB, Devenny DA, Krinsky-McHale SJ, Jenkins EC, Urv TK, Wegiel J, et al. Alzheimer's Disease in Adults with Down Syndrome. Int Rev Res Ment Retard. 2008 Jan 1. 36:103-145. [Medline].
Lubin RA. Kiele M. Janicki MP, Wisnieski MH. Epidemiology of Aging in Developmental Disabilities. Baltimore: Paul H Brookes Publishing Co; 1985. 95-113.
Braddock D. Aging and developmental disabilities: demographic and policy issues affecting American families. Ment Retard. 1999 Apr. 37(2):155-61. [Medline].
Strauss D, Eyman RK. Mortality of people with mental retardation in California with and without Down syndrome, 1986-1991. Am J Ment Retard. 1996 May. 100(6):643-53. [Medline].
Dybwad G. Administrative and legislative problems in the care of the adult and aged mental retardate. Am J Ment Defic. 1962 Mar. 66:716-22. [Medline].
Dybwad R, Dybwad G. Foreword. 1992. 52:
Head E, Lott IT, Patterson D, Doran E, Haier RJ. Possible compensatory events in adult Down syndrome brain prior to the development of Alzheimer disease neuropathology: targets for nonpharmacological intervention. J Alzheimers Dis. 2007 Mar. 11(1):61-76. [Medline].
Devenny DA, Krinsky-McHale SJ, Sersen G, Silverman WP. Sequence of cognitive decline in dementia in adults with Down's syndrome. J Intellect Disabil Res. 2000 Dec. 44 ( Pt 6):654-65. [Medline].
Strydom A, Chan T, King M, Hassiotis A, Livingston G. Incidence of dementia in older adults with intellectual disabilities. Res Dev Disabil. 2013 Jun. 34(6):1881-5. [Medline].
Shooshtari S, Martens PJ, Burchill CA, Dik N, Naghipur S. Prevalence of Depression and Dementia among Adults with Developmental Disabilities in Manitoba, Canada. Int J Family Med. 2011. 2011:319574. [Medline]. [Full Text].
Strydom A, Livingston G, King M, Hassiotis A. Prevalence of dementia in intellectual disability using different diagnostic criteria. Br J Psychiatry. 2007 Aug. 191:150-7. [Medline].
Durham NH. The International Exchange of Experts and Information in Rehabilitation, Evenhuis. University of New Hampshire: 1997.
Janicki MP, Dalton AJ. Prevalence of dementia and impact on intellectual disability services. Ment Retard. 2000 Jun. 38(3):276-88. [Medline].
Cole G, Neal JW, Fraser WI, Cowie VA. Autopsy findings in patients with mental handicap. J Intellect Disabil Res. 1994 Feb. 38 ( Pt 1):9-26. [Medline].
Schupf N, Pang D, Patel BN, Silverman W, Schubert R, Lai F, et al. Onset of dementia is associated with age at menopause in women with Down's syndrome. Ann Neurol. 2003 Oct. 54(4):433-8. [Medline].
Schupf N, Winsten S, Patel B, Pang D, Ferin M, Zigman WB, et al. Bioavailable estradiol and age at onset of Alzheimer's disease in postmenopausal women with Down syndrome. Neurosci Lett. 2006 Oct 9. 406(3):298-302. [Medline].
Devenny DA, Zimmerli EJ, Kittler P, Krinsky-McHale SJ. Cued recall in early-stage dementia in adults with Down's syndrome. J Intellect Disabil Res. 2002 Sep. 46:472-83. [Medline].
Evenhuis HM. The natural history of dementia in Down's syndrome. Arch Neurol. 1990 Mar. 47(3):263-7. [Medline].
Devenny DA, Silverman WP, Hill AL, Jenkins E, Sersen EA, Wisniewski KE. Normal ageing in adults with Down's syndrome: a longitudinal study. J Intellect Disabil Res. 1996 Jun. 40 ( Pt 3):208-21. [Medline].
Krinsky-McHale SJ, Devenny DA, Kittler P, Silverman W. Selective attention deficits associated with mild cognitive impairment and early stage Alzheimer's disease in adults with Down syndrome. Am J Ment Retard. 2008 Sep. 113(5):369-86. [Medline].
Urv TK, Zigman WB, Silverman W. Maladaptive behaviors related to dementia status in adults with Down syndrome. Am J Ment Retard. 2008 Mar. 113(2):73-86. [Medline].
Lazenby T. The impact of aging on eating, drinking, and swallowing function in people with Down's syndrome. Dysphagia. 2008 Mar. 23(1):88-97. [Medline].
Möller JC, Hamer HM, Oertel WH, Rosenow F. Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS). Seizure. 2002 Apr. 11 Suppl A:303-5. [Medline].
De Simone R, Daquin G, Genton P. Senile myoclonic epilepsy in Down syndrome: a video and EEG presentation of two cases. Epileptic Disord. Sep 2006. 8(3):223-7.
Cournot M, Marquié JC, Ansiau D, Martinaud C, Fonds H, Ferrières J, et al. Relation between body mass index and cognitive function in healthy middle-aged men and women. Neurology. 2006 Oct 10. 67(7):1208-14. [Medline].
Deary IJ, Whalley LJ, Batty GD, Starr JM. Physical fitness and lifetime cognitive change. Neurology. 2006 Oct 10. 67(7):1195-200. [Medline].
Regan C, Katona C, Walker Z, Hooper J, Donovan J, Livingston G. Relationship of vascular risk to the progression of Alzheimer disease. Neurology. 2006 Oct 24. 67(8):1357-62. [Medline].
Alzheimer's Association. Screening tests for dementia. Available at http://www.alz.org. Accessed: 2006.
Friedman DL, Kastner T, Pond WS, O'Brien DR. Thyroid dysfunction in individuals with Down syndrome. Arch Intern Med. 1989 Sep. 149(9):1990-3. [Medline].
Alzheimer's Association. Tau/Abeta42 test. Available at http://www.alz.org. Accessed: 2006.
Petersen RC, Trojanowski JQ. Use of Alzheimer disease biomarkers: potentially yes for clinical trials but not yet for clinical practice. JAMA. 2009 Jul 22. 302(4):436-7. [Medline]. [Full Text].
Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA. 2009 Jul 22. 302 (4):385-93. [Medline].
Henriksen K, O'Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A, et al. The future of blood-based biomarkers for Alzheimer's disease. Alzheimers Dement. 2014 Jan. 10 (1):115-31. [Medline].
Jenkins EC, Velinov MT, Ye L, Gu H, Li S, Jenkins EC Jr, et al. Telomere shortening in T lymphocytes of older individuals with Down syndrome and dementia. Neurobiol Aging. 2006 Jul. 27 (7):941-5. [Medline].
Schapiro MB. Neuroimaging in Adults with Down Syndrome. Berg JM, Karlinsky H, Holland AJ. Alzheimer Disease, Down Syndrome and Their Relationship. New York, NY: Oxford University Press; 1996. 173-197.
Beacher F, Daly E, Simmons A, Prasher V, Morris R, Robinson C. Alzheimer's disease and Down's syndrome: an in vivo MRI study. Psychol Med. 2009 Apr. 39(4):675-84. [Medline].
Beacher F, Daly E, Simmons A, Prasher V, Morris R, Robinson C. Brain anatomy and ageing in non-demented adults with Down's syndrome: an in vivo MRI study. Psychol Med. 2010 Apr. 40(4):611-9. [Medline].
LeMay M, Alvarez N. The relationship between enlargement of the temporal horns of the lateral ventricles and dementia in aging patients with Down syndrome. Neuroradiology. 1990. 32(2):104-7. [Medline].
Powell D, Caban-Holt A, Jicha G, Robertson W, Davis R, Gold BT, et al. Frontal white matter integrity in adults with Down syndrome with and without dementia. Neurobiol Aging. 2014 Jul. 35 (7):1562-9. [Medline].
Schapiro MB, Ball MJ, Grady CL, Haxby JV, Kaye JA, Rapoport SI. Dementia in Down's syndrome: cerebral glucose utilization, neuropsychological assessment, and neuropathology. Neurology. 1988 Jun. 38(6):938-42. [Medline].
Shipley SM, Frederick MC, Filley CM, Kluger BM. Potential for misdiagnosis in community-acquired PET scans for dementia. Neurol Clin Pract. 2013 Aug. 3(4):305-312. [Medline]. [Full Text].
Landt J, D'Abrera JC, Holland AJ, Aigbirhio FI, Fryer TD, Canales R, et al. Using positron emission tomography and Carbon 11-labeled Pittsburgh Compound B to image Brain Fibrillar β-amyloid in adults with down syndrome: safety, acceptability, and feasibility. Arch Neurol. 2011 Jul. 68 (7):890-6. [Medline].
Handen BL, Cohen AD, Channamalappa U, Bulova P, Cannon SA, Cohen WI, et al. Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B. Alzheimers Dement. 2012 Nov. 8 (6):496-501. [Medline].
Sabbagh MN, Fleisher A, Chen K, Rogers J, Berk C, Reiman E, et al. Positron emission tomography and neuropathologic estimates of fibrillar amyloid-β in a patient with Down syndrome and Alzheimer disease. Arch Neurol. 2011 Nov. 68 (11):1461-6. [Medline].
Jennings D, Seibyl J, Sabbagh M, Lai F, Hopkins W, Bullich S, et al. Age dependence of brain β-amyloid deposition in Down syndrome: An [18F]florbetaben PET study. Neurology. 2015 Feb 3. 84 (5):500-7. [Medline].
Hartley SL, Handen BL, Devenny DA, Hardison R, Mihaila I, Price JC, et al. Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome. Brain. 2014 Sep. 137 (Pt 9):2556-63. [Medline].
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
Carrillo MC, Dean RA, Nicolas F, Miller DS, Berman R, Khachaturian Z. Revisiting the framework of the National Institute on Aging-Alzheimer's Association diagnostic criteria. Alzheimers Dement. 2013 Sep. 9(5):594-601. [Medline].
Joachim CL, Morris JH, Selkoe DJ. Clinically diagnosed Alzheimer's disease: autopsy results in 150 cases. Ann Neurol. 1988 Jul. 24(1):50-6. [Medline].
Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001 May 8. 56(9):1143-53. [Medline].
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul. 34(7):939-44. [Medline].
Aylward EH, Burt DB, Thorpe LU, Lai F, Dalton A. Diagnosis of dementia in individuals with intellectual disability. J Intellect Disabil Res. 1997 Apr. 41 ( Pt 2):152-64. [Medline].
Aman MG. Assessing Psychopathology and Behavior Problems in Persons With Mental Retardation: A Review of Available Instruments. DIANE Publishing; 1994.
Shultz J, Aman M, Kelbley T, LeClear Wallace C, Burt DB, Primeaux-Hart S, et al. Evaluation of screening tools for dementia in older adults with mental retardation. Am J Ment Retard. 2004 Mar. 109(2):98-110. [Medline].
Gedye A. DSDS Dementia Scale for Down's Syndrome. Vancouver, British Columbia: 1995. 1-67.
Huxley A, Prasher VP, Haque MS. The dementia scale for Down's syndrome. J Intellect Disabil Res. 2000 Dec. 44 ( Pt 6):697-8. [Medline].
Evenhuis, H. M., Kengen, M. M. F. & Eurlings, H. A. L. (1990) Demential Questionnaire for Mentally Retarded Persons. Zwannerdam, The Neederlands: Hooge Burch Institute for Mentally Retarded People.
Reiss S. Reiss Screen for Maladaptive Behavior. Worthington OH: International Diagnostic System, Inc; 1987.
Zelinski EM, Gilewski MJ. Assessment of memory complaints by rating scales and questionnaires. Psychopharmacol Bull. 1988. 24(4):523-9. [Medline].
Prasher VP. Review of donepezil, rivastigmine, galantamine and memantine for the treatment of dementia in Alzheimer's disease in adults with Down syndrome: implications for the intellectual disability population. Int J Geriatr Psychiatry. 2004 Jun. 19(6):509-15. [Medline].
Prasher VP, Adams C, Holder R. Long term safety and efficacy of donepezil in the treatment of dementia in Alzheimer's disease in adults with Down syndrome: open label study. Int J Geriatr Psychiatry. 2003 Jun. 18(6):549-51. [Medline].
Mohan M, Carpenter PK, Bennett C. Donepezil for dementia in people with Down syndrome. Cochrane Database Syst Rev. 2009 Jan 21. CD007178. [Medline].
Prasher VP, Fung N, Adams C. Rivastigmine in the treatment of dementia in Alzheimer's disease in adults with Down syndrome. Int J Geriatr Psychiatry. 2005 May. 20(5):496-7. [Medline].
Matsunaga S, Kishi T, Iwata N. Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis. PLoS One. 2015. 10 (4):e0123289. [Medline].
Schneider LS, Dagerman KS, Higgins JP, McShane R. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol. 2011 Aug. 68 (8):991-8. [Medline].
Boada-Rovira M, Hernández-Ruiz I, Badenas-Homiar S, Buendía-Torras M, Tárraga-Mestre L. [Clinical-therapeutic study of dementia in people with Down syndrome and the effectiveness of donepezil in this population]. Rev Neurol. 2005 Aug 1-15. 41(3):129-36. [Medline].
Hemingway-Eltomey JM, Lerner AJ. Adverse effects of donepezil in treating Alzheimer's disease associated with Down's syndrome. Am J Psychiatry. 1999 Sep. 156(9):1470. [Medline].
Kishnani PS, Spiridigliozzi GA, Heller JH, Sullivan JA, Doraiswamy PM, Krishnan KR. Donepezil for Down's syndrome. Am J Psychiatry. 2001 Jan. 158(1):143. [Medline].
Kishnani PS, Sullivan JA, Walter BK, Spiridigliozzi GA, Doraiswamy PM, Krishnan KR. Cholinergic therapy for Down's syndrome. Lancet. 1999 Mar 27. 353(9158):1064-5. [Medline].
Lott IT, Osann K, Doran E, Nelson L. Down syndrome and Alzheimer disease: response to donepezil. Arch Neurol. 2002 Jul. 59(7):1133-6. [Medline].
Prasher VP, Huxley A, Haque MS,. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study. Int J Geriatr Psychiatry. 2002 Mar. 17(3):270-8. [Medline].
Kondoh T, Kanno A, Itoh H, Nakashima M, Honda R, Kojima M. Donepezil significantly improves abilities in daily lives of female Down syndrome patients with severe cognitive impairment: a 24-week randomized, double-blind, placebo-controlled trial. Int J Psychiatry Med. 2011. 41(1):71-89. [Medline].
Mohan M, Bennett C, Carpenter PK. Rivastigmine for dementia in people with Down syndrome. Cochrane Database Syst Rev. 2009 Jan 21. CD007658. [Medline].
Mohan M, Bennett C, Carpenter PK. Galantamine for dementia in people with Down syndrome. Cochrane Database Syst Rev. 2009 Jan 21. CD007656. [Medline].
Livingstone N, Hanratty J, McShane R, Macdonald G. Pharmacological interventions for cognitive decline in people with Down syndrome. Cochrane Database Syst Rev. 2015 Oct 29. 10:CD011546. [Medline].
Mohan M, Bennett C, Carpenter PK. Memantine for dementia in people with Down syndrome. Cochrane Database Syst Rev. 2009 Jan 21. CD007657. [Medline].
Hanney M, Prasher V, Williams N, Jones EL, Aarsland D, Corbett A, et al. Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial. Lancet. 2012 Feb 11. 379(9815):528-36. [Medline].
McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology. 1996 Aug. 47(2):425-32. [Medline].
Aisen PS, Saumier D, Briand R, Laurin J, Gervais F, Tremblay P, et al. A Phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurology. 2006 Nov 28. 67(10):1757-63. [Medline].
Gualandri W, Gualandri L, Demartini G, Esposti R, Marthyn P, Volontè S. Redox balance in patients with Down's syndrome before and after dietary supplementation with alpha-lipoic acid and L-cysteine. Int J Clin Pharmacol Res. 2003. 23(1):23-30. [Medline].
Sauer J, Tabet N, Howard R. Alpha lipoic acid for dementia. Cochrane Database Syst Rev. 2004. (1):CD004244.
De Falco FA, D'Angelo E, Grimaldi G, Scafuro F, Sachez F, Caruso G. [Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome]. Clin Ter. 1994 Feb. 144(2):123-7. [Medline].
Pueschel SM. The effect of acetyl-L-carnitine administration on persons with Down syndrome. Res Dev Disabil. 2006 Nov-Dec. 27(6):599-604. [Medline].
Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DL. Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. Am J Med Genet A. 2011 Aug. 155A(8):1939-48. [Medline].
Jansen SL, Forbes DA, Duncan V, Morgan DG. Melatonin for cognitive impairment. Cochrane Database Syst Rev. 2006 Jan 25. CD003802. [Medline].
Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002 Jun 26. 287(24):3223-9. [Medline].
MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6. 360(9326):23-33. [Medline].
Tabet N, Birks J, Grimley Evans J. Vitamin E for Alzheimer's disease. Cochrane Database Syst Rev. 2000. (4):CD002854.
Fillon-Emery N, Chango A, Mircher C, Barbé F, Bléhaut H, Herbeth B, et al. Homocysteine concentrations in adults with trisomy 21: effect of B vitamins and genetic polymorphisms. Am J Clin Nutr. 2004 Dec. 80(6):1551-7. [Medline].
Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008 Dec 10. 1-23. [Medline].
Snitz BE, O'Meara ES, Carlson MC, Arnold AM, Ives DG, Rapp SR, et al. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA. 2009 Dec 23. 302(24):2663-70. [Medline]. [Full Text].
Don Francesco R, Dell’uomo A. gingko biloba in Down syndrome. Phytomedicine. Sept 11 2004. (6):469.
Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12. 355(15):1525-38. [Medline].
Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997 Apr 24. 336(17):1216-22. [Medline].
Birks J, Flicker L. Selegiline for Alzheimer's disease. Cochrane Database Syst Rev. 2003. CD000442. [Medline].
McCarron M, Gill M, McCallion P, Begley C. Health co-morbidities in ageing persons with Down syndrome and Alzheimer's dementia. J Intellect Disabil Res. 2005 Jul. 49:560-6. [Medline].
Volicer L, Rheaume Y, Brown J, Fabiszewski K, Brady R. Hospice approach to the treatment of patients with advanced dementia of the Alzheimer type. JAMA. 1986 Oct 24-31. 256(16):2210-3. [Medline].
Green RC, DeKosky ST. Primary prevention trials in Alzheimer disease. Neurology. 2006 Nov 14. 67(9 Suppl 3):S2-5. [Medline].
Vellas B, Thal L. Prevention trials in the field of Alzheimer disease. Neurol. Nov 14 2006. 67(9)(suppl 3):
Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology. 2006 Oct 24. 67(8):1370-6. [Medline].
Aisen PS, Dalton AJ, Sano M. Design and implementation of a multicenter trial of vitamin E in aging individuals with down syndrome. J of Policy and Pract in Intellect Disabil 2. 86-93.
Mittelman MS, Haley WE, Clay OJ, Roth DL. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology. 2006 Nov 14. 67(9):1592-9. [Medline].
Jellinger KA, Bancher C. Neuropathology of Alzheimer's disease: a critical update. J Neural Transm Suppl. 1998. 54:77-95. [Medline].
Ikeda S, Yanagisawa N, Allsop D, Glenner GG. Evidence of amyloid beta-protein immunoreactive early plaque lesions in Down's syndrome brains. Lab Invest. Jul 1989. 61(1):133-7.
Rumble B, Retallack R, Hilbich C, et al. Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease. N Engl J Med. Jun 1 1989. 320(22):1446-52.
Leverenz JB, Raskind MA. Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Exp Neurol. 1998 Apr. 150 (2):296-304. [Medline].
Mann DM. The pathological association between Down syndrome and Alzheimer disease. Mech Ageing Dev. 1988 May. 43 (2):99-136. [Medline].
Armstrong RA. Size frequency distributions of β-amyloid (Aβ) deposits: a comparative study of four neurodegenerative disorders. Folia Neuropathol. 2012. 50 (3):240-9. [Medline].
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011 Sep. 1 (1):a006189. [Medline].
Leverenz JB, Raskind MA. Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Exp Neurol. 1998 Apr. 150 (2):296-304. [Medline].
Wisniewski HM, Wegiel J. The neuropathology of Alzheimer's disease. Neuroimaging Clin N Am. 1995 Feb. 5 (1):45-57. [Medline].
Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 2013 Dec. 45 (12):1452-8. [Medline].
Wisniewski KE, Wisniewski HM, Wen GY. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol. 1985 Mar. 17 (3):278-82. [Medline].
Margallo-Lana ML, Moore PB, Kay DW, Perry RH, Reid BE, Berney TP, et al. Fifteen-year follow-up of 92 hospitalized adults with Down's syndrome: incidence of cognitive decline, its relationship to age and neuropathology. J Intellect Disabil Res. 2007 Jun. 51 (Pt. 6):463-77. [Medline].
Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci. 1991 Oct. 12 (10):383-8. [Medline].
Cataldo AM, Petanceska S, Terio NB, Peterhoff CM, Durham R, Mercken M, et al. Abeta localization in abnormal endosomes: association with earliest Abeta elevations in AD and Down syndrome. Neurobiol Aging. 2004 Nov-Dec. 25 (10):1263-72. [Medline].
Mehta PD, Dalton AJ, Mehta SP, Kim KS, Sersen EA, Wisniewski HM. Increased plasma amyloid beta protein 1-42 levels in Down syndrome. Neurosci Lett. 1998 Jan 23. 241(1):13-6. [Medline].
Schupf N, Patel B, Pang D, Zigman WB, Silverman W, Mehta PD, et al. Elevated plasma beta-amyloid peptide Abeta(42) levels, incident dementia, and mortality in Down syndrome. Arch Neurol. 2007 Jul. 64(7):1007-13. [Medline]. [Full Text].
Neale N, Padilla C, Fonseca LM, Holland T, Zaman S. Neuroimaging and other modalities to assess Alzheimer's disease in Down syndrome. Neuroimage Clin. 2018. 17:263-271. [Medline].

Media Gallery

CT scan of a man who has Down syndrome confirmed by chromosomal analysis. He has a long history of mental deterioration with progressive loss of ability to perform his usual activities. The CT scan, obtained when the patient was aged 60 years and exhibiting advanced signs of Alzheimer disease, shows several calcified areas in the basal ganglia plus diffuse cortical atrophy and enlargement of the ventricular system. The bilateral symmetric calcifications are a frequent finding in this condition.
CT scan of a man who has Down syndrome confirmed by chromosomal analysis. He has a long history of mental deterioration with progressive loss of ability to perform his usual activities. The CT scan, obtained when the patient was aged 60 years and exhibiting advanced signs of Alzheimer disease, shows several calcified areas in the basal ganglia plus diffuse cortical atrophy and enlargement of the ventricular system. The bilateral symmetric calcifications are a frequent finding in this condition.
CT scan of a man who has Down syndrome confirmed by chromosomal analysis. He has a long history of mental deterioration with progressive loss of ability to perform his usual activities. The CT scan, obtained when the patient was aged 60 years and exhibiting advanced signs of Alzheimer disease, shows several calcified areas in the basal ganglia plus diffuse cortical atrophy and enlargement of the ventricular system. The bilateral symmetric calcifications are a frequent finding in this condition.
CT scan of a 62-year-old man with Down syndrome confirmed by chromosomal analysis. This CT scan was obtained when he was showing signs of moderate-to-advanced Alzheimer disease. The CT scan shows marked, diffuse enlargement of the ventricular system and generalized atrophy of the cerebral cortex.
CT scan of a 62-year-old man with Down syndrome confirmed by chromosomal analysis. This CT scan was obtained when he was showing signs of moderate-to-advanced Alzheimer disease. The CT scan shows marked, diffuse enlargement of the ventricular system and generalized atrophy of the cerebral cortex.
CT scan of a 62-year-old man with Down syndrome confirmed by chromosomal analysis. This CT scan was obtained when he was showing signs of moderate-to-advanced Alzheimer disease. The CT scan shows marked, diffuse enlargement of the ventricular system and generalized atrophy of the cerebral cortex.

of 6

What is a case study that illustrates typical Alzheimer disease (AD) in Down syndrome (DS) progression?

Answer

Related Questions:

References

Tables

Contributor Information and Disclosures