Adulti con sindrome di DownAngelo Carfì

Fondazione Policlinico Universitario «A. Gemelli» IRCCS, Roma

Dove lavoro

Dove lavoro

Con chi

Scopo della presentazione

Programma

•Epidemiologia della DS

•Pratica clinica−Dati del nostro centro−Argomenti caldi−Uso di farmaci−Spunti di orientamento generale sull’approccio

agli adulti

•Campo aperto alla ricerca

Programma

•Epidemiologia della DS

•Pratica clinica−Dati del nostro centro−Argomenti caldi−Uso di farmaci−Spunti di orientamento generale sull’approccio

agli adulti

•Campo aperto alla ricerca

Epidemiologia – Natalità DS stimata in U.S.

de Graaf G, Buckley F, Skotko BG. Estimation of the number of people with Down syndrome in the United States. Genet Med. 2017 Apr;19(4):439-447. doi: 10.1038/gim.2016.127. Epub 2016 Sep 8. PubMed PMID: 27608174.

Birth control and family planning

introduced

Modern birth control pills

and IUDs

Fertility rate increased

surrounding WWII

Women begin to wait until

later years to have children

DS-related selective

termination

Epidemiologia – Prevalenza di DS in 9 statiU.S.

0

50000

100000

150000

200000

250000

1950 1960 1970 1980 1990 2000 2010

Historical development in number of people with DS in the U.S. by age group

0-4 5-9 10-14 15-19 20-24 25-29 30-39 40-49 50-59 >=60 yrs

de Graaf G, Buckley F, Dever J, Skotko BG. Estimation of live birth and population prevalence of Down syndrome in nine U.S. states. Am J Med Genet A. 2017 Oct;173(10):2710-2719. doi: 10.1002/ajmg.a.38402.

0

50000

100000

150000

200000

250000

1950 1960 1970 1980 1990 2000 2010

Historical development in number of people with DS in the U.S. by age group

0-4 5-9 10-14 15-19 20-24 25-29 30-39 40-49 50-59 >=60 yrs

de Graaf G, Buckley F, Dever J, Skotko BG. Estimation of live birth and population prevalence of Down syndrome in nine U.S. states. Am J Med Genet A. 2017 Oct;173(10):2710-2719. doi: 10.1002/ajmg.a.38402.

PED

???

Epidemiologia – Prevalenza di DS in 9 statiU.S.

Epidemiologia – Curva di sopravvivenza stimata in U.S.

Epidemiologia – Curva di sopravvivenza stimata in U.S.

Epidemiologia – dati U.S.

PED ???

Dati italiani – 38000 persone Down in Italia

Rosano A. Survival of Persons with Down Syndrome in Italy. Journal of Intellectual Disability - Diagnosis and Treatment, 2014, 2, 119-123 119

Programma

•Epidemiologia della DS

•Pratica clinica−Dati del nostro centro−Argomenti caldi−Uso di farmaci−Spunti di orientamento generale sull’approccio

agli adulti

•Campo aperto alla ricerca

Total 18-39 years >40 years Female Male

n=421n=234

(55.6%)

n=187

(44.4%)

n=214

(51.1%)

n=207

(48.9%)

Demographics

Age 38.3 ± 12.8 28.6 ± 6.2 50.6 ± 7.1 39.9 ± 12.6 36.7 ± 12.9

Sex (female) 214 (50.8%) 106 (45.3%) 108 (57.8%)

Number of diseases 3.52 ± 1.79 3.32 ± 1.72 3.77 ± 1.85 3.58 ± 1.83 3.46 ± 1.75

0 7 (1.66%) 5 (2.14%) 2 (1.07%) 3 (1.4%) 4 (1.93%)

1 40 (9.5%) 28 (12.0%) 12 (6.42) 20 (9.35%) 20 (9.66%)

2 or more 374 (88.8%) 201 (85.9%) 173 (92.5%) 191 (89.3%) 183 (88.4%)

Number of drugs 2.09 ± 1.96 1.55 ± 1.72 2.77 ± 2.04 2.26 ± 1.89 1.92 ± 2.03

Neurotropic drugs 0.7 ± 1.05 0.39 ± 0.8 1.08 ± 1.20 0.79 ± 1.16 0.6 ± 0.92

Polypharmacy 44 (10.5%) 16 (6.84%) 28 (15%) 24 (11.2%) 20 (9.66%)

Disturbi della vista

Glasson EJ et al The triple challenges associated with age-related comorbidities in Down syndrome. J Intellect Disabil Res. 2014 Apr;58(4):393-8. PMID: 23510031.

Disturbi dell’udito

Picciotti PM, Carfì A, et al. Audiologic Assessment in Adults With Down Syndrome. Am JIntellect Dev Disabil. 2017 Jul;122(4):333-341.

Osteoporosi

19.6

4.3

15.2

3.9

6.2

2.4

4.9

1.3

17.0

2.3

12.3

3.3

any neck spine

M F M F M F

0

5

10

15

20

Pre

va

len

ce

(%

)

Group

NHANES

DS

• DS n = 398• NHANES n = 2705• vBMD stimata con

BMAD• Diagnosi secondo

linee guida WHO

Carfì A, et al. Unpublished data

Osteoporosi – Colonna lombare

0.10

0.15

0.20

0.25

20−29 30−39 40−49 50−59 60−69 70−79

Age group

Lum

bar

sp

ine

BM

AD

Group: NHANES DSM

0.10

0.15

0.20

0.25

20−29 30−39 40−49 50−59 60−69 70−79

Age groupL

um

bar

sp

ine

BM

AD

Group: NHANES DSF

9.9

2.4

12.2

1.1

25.7

1.8

35.7

5.0 7.2 5.5

0

10

20

30

40

50

20−29 30−39 40−49 50−59 60−69 70−79

Age group

Pre

va

len

ce

(%

)

10.1

2.5

19.0

1.8

10.9

2.6

10.8 4.2

8.1

18.6

0

10

20

30

40

50

20−29 30−39 40−49 50−59 60−69 70−79

Age group

Pre

va

len

ce

(%

)

Carfì A, et al. Unpublished data

Osteoporosi – Collo femorale

0.1

0.2

0.3

20−29 30−39 40−49 50−59 60−69 70−79

Age group

Fe

mo

ral ne

ck B

MA

D

Group: NHANES DSM

0.1

0.2

0.3

20−29 30−39 40−49 50−59 60−69 70−79

Age groupF

em

ora

l ne

ck B

MA

D

Group: NHANES DSF

2.5 1.8 4.1 0.5

5.6 0.5

21.4

1.0 6.2 7.3

0

10

20

30

40

50

20−29 30−39 40−49 50−59 60−69 70−79

Age group

Pre

va

len

ce

(%

)

2.6 0.5 2.4 0.5

13.0

2.8 0.6 1.8 7.8

0

10

20

30

40

50

20−29 30−39 40−49 50−59 60−69 70−79

Age group

Pre

va

len

ce

(%

)

Carfì A, et al. Unpublished data

Programma

•Epidemiologia della DS

•Pratica clinica−Dati del nostro centro−Argomenti caldi−Uso di farmaci−Spunti di orientamento generale sull’approccio

agli adulti

•Campo aperto alla ricerca

Cardiopatia congenita

Yang Q, Rasmussen SA, Friedman JM. Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet. 2002 Mar 23;359(9311):1019-25.PMID: 11937181.

Cardiopatia congenita

• Pueschel & Werner 1994:

• 36 soggetti adulti

• 20 (55.5%) ecocardiogramma alterato

• 16 (44.4%) prolasso mitralico, 3 di questi con insufficienza aorticacontro il 5-10% della popolazione generale

Cardiopatia congenita

• Prevalenza stimata del 40%

• Sesso femminile più prevalente

Baraona F et al. Hospitalizations and mortality in the United States for adults with Down syndromeand congenital heart disease. Am J Cardiol. 2013 Apr 1;111(7):1046-51. PMID: 23332593.

Baraona F et al. Hospitalizations and mortality in the United States for adults with Down syndromeand congenital heart disease. Am J Cardiol. 2013 Apr 1;111(7):1046-51. PMID: 23332593.

Cardiopatia congenita

Baraona F et al. Hospitalizations and mortality in the United States for adults with Down syndromeand congenital heart disease. Am J Cardiol. 2013 Apr 1;111(7):1046-51. PMID: 23332593.

Cardiopatia congenita

Disturbi dell’umore - Prevalenza

• Mantry et al. 2008: • studio su 134

soggetti con FU a 2 anni

• Episodiodepressivo nel5.2% del campione• 5.5 % tra 16-

44 anni

• 4.9% >45 anni

Disturbi dell’umore – Presentazione clinicaMyers and Pueschel (1995)

22 cases with major depression with a mean age of 28.5 years.

• loss of interest (95.4%).

• sleeping disorders and decreased appetite or weight loss (both in 81.8%),

• agitation (72%),

• anxiety (40.9%),

• fatigue (36.3%) and

• memory deficits (22.7%).

• Hallucinations occurred in 10 out of 22 (45.5%) cases with DS and major depression.

• attempted suicide was observed in 5 out of 22 cases (27.3%)

Cooper and Collacott (1994)

42 adults who had experienced at least one depressive episode.

• reduced interest and pleasure (91%),

• depressed affect (88%),

• psychomotor retardation (59%),

• tearfulness (57%),

• reduced energy (57%),

• loss of appetite (55%),

• sleep disturbance (46%),

• hypochondriasis (36%),

• aggression or tantrums (36%) and

• reduced speech (34%).

• Hallucinations occurred in three individuals (5%).

Disturbi dell’umore – depression/regression

• “Acute regression” – Mircher C et al. 2017

• “Down syndrome disintegrative disorder” – Worley G et al. 2015

• “New-Onset Autistic Regression”

• “Regression, Dementia, and Insomnia”

• “Catatonia” – Ghaziuddin N et al. 2015

• “Rapid clinical deterioration” – Jacobs J et al. 2016

Mircher C, et al. Acute Regression in Young People with Down Syndrome. Brain Sci. 2017 May 27;7(6). PMID: 28555009

Disturbi dell’umore – depression/regression

• Significant and precipitous loss of activities of daily living and baseline skills within 6 months

• Perceived decline in cognition

• Unexplained decompensation in behavioral functioning and mood

• Significant loss of speech

• Ages 10–30 years and usually post-pubertal at the time of onset

• Prior to onset, no history of autism spectrum disorder, infantile spasms, seizure disorder, or significant psychopathology

Jacobs J et al. Rapid clinical deterioration in an individual with Down syndrome. Am J Med Genet A. 2016 Jul;170(7):1899-902. PMID: 27149638.

Disturbi dell’umore – depression/regression

Mircher C, et al. Acute Regression in Young People with Down Syndrome. Brain Sci. 2017 May 27;7(6). PMID: 28555009

Disturbi dell’umore – depression/regression

Mircher C, et al. Acute Regression in Young People with Down Syndrome. Brain Sci. 2017 May 27;7(6). PMID: 28555009

Disturbi dell’umore – depression/regression

Ghaziuddin N, Nassiri A, Miles JH. Catatonia in down syndrome; a treatablecause of regression. Neuropsychiatr Dis Treat. 2015;2(11):941–942.

EpilessiaBimodal distribution of seizure problems in patients with Down syndrome.

• In the first year of life, infantile spasms and the entity of tonic-clonicseizures with myoclonus accounted for 40% of those with seizures.

• Few seizures developed from the age of 1 to 19 years, whereas

• between 20 and 30 years of age a further 40% of the patients began having seizures.

Pueschel SM, Louis S, McKnight P. Seizure disorders in Down syndrome. Arch Neurol. 1991 Mar;48(3):318-20. PubMed PMID: 1825777.

Epilessia - caratteristiche

•Myoclonus and seizures are very common in DS dementia

• described as the presenting symptom in some cases, especially in those with severe ID

•Also predictive of rate of decline

• so strongly associated with AD in older individuals with DS that the onset of seizures in older age should trigger an assessment for dementia

• Seizures are commonly myoclonic or tonic-clonic types• earlier picture characterized by myoclonic jerks on awakening• progression to generalized tonic-clonic seizures.

Zis P, Strydom A. Clinical aspects and biomarkers of Alzheimer's disease in Down syndrome. Free Radic Biol Med. 2018 Jan;114:3-9. doi: 10.1016/j

Epilessia

Zis P, Strydom A. Clinical aspects and biomarkers of Alzheimer's disease in Down syndrome. Free Radic Biol Med. 2018 Jan;114:3-9. doi: 10.1016/j

Programma

•Epidemiologia della DS

•Pratica clinica−Dati del nostro centro−Argomenti caldi−Uso di farmaci−Spunti di orientamento generale sull’approccio

agli adulti

•Campo aperto alla ricerca

Programma

•Epidemiologia della DS

•Pratica clinica−Dati del nostro centro−Argomenti caldi−Uso di farmaci−Spunti di orientamento generale sull’approccio

agli adulti

•Campo aperto alla ricerca

Programma

•Epidemiologia della DS

•Pratica clinica−Dati del nostro centro−Argomenti caldi−Uso di farmaci−Spunti di orientamento generale sull’approccio

agli adulti

•Campo aperto alla ricerca

Composizione corporea – Sarcopenia

SINDROME DI DOWN (n = 45) NANHES (n = 1192)

M

n=29

(64,4%)

F

n=16

(35,6%)

TOT

n = 45

M

n=625

(52,4%)

F

n=567

(47,6%)

TOT

n=1192

Age 37 ± 14 35 ± 13 35 ± 13 41 ± 14 40 ± 14 40 ± 14

Aree di interesse (oltre alla demenza)

•Disturbi comportamentali –personalizzazione delle terapie

•“Grandi assenti”• Ipertensione – malattia cardiovascolare (?)•Neoplasie

•Metabolismo

•Disturbi gastrointestinali

Grazie!angelo.carfi@policlinicogemelli.it