Timing of Alzheimer's Disease by Intellectual Disability Level in Down Syndrome.

Humans Alzheimer Disease / complications Down Syndrome / complications Intellectual Disability / complications Cognitive Dysfunction / psychology Biomarkers Amyloid beta-Peptides tau Proteins Positron-Emission Tomography
Alzheimer’s disease Down syndrome amyloid cognitive dementia imaging intellectual memory tau

Journal

Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863

Informations de publication

Date de publication:
2023
Historique:
medline: 5 9 2023
pubmed: 24 7 2023
entrez: 24 7 2023
Statut: ppublish

Résumé

Trisomy 21 causes Down syndrome (DS) and is a recognized cause of early-onset Alzheimer's disease (AD). The current study sought to determine if premorbid intellectual disability level (ID) was associated with variability in age-trajectories of AD biomarkers and cognitive impairments. General linear mixed models compared the age-trajectory of the AD biomarkers PET Aβ and tau and cognitive decline across premorbid ID levels (mild, moderate, and severe/profound), in models controlling trisomy type, APOE status, biological sex, and site. Analyses involved adults with DS from the Alzheimer's Biomarkers Consortium-Down Syndrome. Participants completed measures of memory, mental status, and visuospatial ability. Premorbid ID level was based on IQ or mental age scores prior to dementia concerns. PET was acquired using [11C] PiB for Aβ, and [18F] AV-1451 for tau. Cognitive data was available for 361 participants with a mean age of 45.22 (SD = 9.92) and PET biomarker data was available for 154 participants. There was not a significant effect of premorbid ID level by age on cognitive outcomes. There was not a significant effect of premorbid ID by age on PET Aβ or on tau PET. There was not a significant difference in age at time of study visit of those with mild cognitive impairment-DS or dementia by premorbid ID level. Findings provide robust evidence of a similar time course in AD trajectory across premorbid ID levels, laying the groundwork for the inclusion of individuals with DS with a variety of IQ levels in clinical AD trials.

Sections du résumé

BACKGROUND
Trisomy 21 causes Down syndrome (DS) and is a recognized cause of early-onset Alzheimer's disease (AD).
OBJECTIVE
The current study sought to determine if premorbid intellectual disability level (ID) was associated with variability in age-trajectories of AD biomarkers and cognitive impairments. General linear mixed models compared the age-trajectory of the AD biomarkers PET Aβ and tau and cognitive decline across premorbid ID levels (mild, moderate, and severe/profound), in models controlling trisomy type, APOE status, biological sex, and site.
METHODS
Analyses involved adults with DS from the Alzheimer's Biomarkers Consortium-Down Syndrome. Participants completed measures of memory, mental status, and visuospatial ability. Premorbid ID level was based on IQ or mental age scores prior to dementia concerns. PET was acquired using [11C] PiB for Aβ, and [18F] AV-1451 for tau.
RESULTS
Cognitive data was available for 361 participants with a mean age of 45.22 (SD = 9.92) and PET biomarker data was available for 154 participants. There was not a significant effect of premorbid ID level by age on cognitive outcomes. There was not a significant effect of premorbid ID by age on PET Aβ or on tau PET. There was not a significant difference in age at time of study visit of those with mild cognitive impairment-DS or dementia by premorbid ID level.
CONCLUSION
Findings provide robust evidence of a similar time course in AD trajectory across premorbid ID levels, laying the groundwork for the inclusion of individuals with DS with a variety of IQ levels in clinical AD trials.

Identifiants

DOI: 10.3233/JAD-230200 PMID: 37482997 PMC: PMC10578224
pubmed: 37482997
pii: JAD230200
doi: 10.3233/JAD-230200
pmc: PMC10578224
doi:

Substances chimiques

Biomarkers 0
Amyloid beta-Peptides 0
tau Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

213-225

Subventions

Organisme : NIA NIH HHS
ID : U01 AG051406
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG051412
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG070028
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105353
Pays : United States
Organisme : NICHD NIH HHS
ID : T32 HD007489
Pays : United States

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Auteurs

Sigan L Hartley (SL)

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
School of Human Ecology, University of Wisconsin-Madison, Madison, WI, USA.

Victoria Fleming (V)

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
School of Human Ecology, University of Wisconsin-Madison, Madison, WI, USA.

Emily K Schworer (EK)

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.

Jamie Peven (J)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Benjamin L Handen (BL)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Sharon Krinsky-McHale (S)

Department of Psychology, New York Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.

Christy Hom (C)

Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.

Laisze Lee (L)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Dana L Tudorascu (DL)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Charles Laymon (C)

Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.

Davneet Minhas (D)

Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.

Weiquan Luo (W)

Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.

Annie Cohen (A)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Shahid Zaman (S)

Cambridgeshire & Peterborough NHS Foundation Trust (CPFT), Elizabeth House, Fulbourn Hospital, Cambridge, UK.
Department of Psychiatry, Cambridge Intellectual & Developmental Disabilities Research Group (CIDDRG), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Beau M Ances (BM)

Department of Neurology, Washington University St. Louis, St. Louis, MO, USA.

Mark Mapstone (M)

Clinical Neurology, University of California, Irvine, Irvine, CA, USA.

Elizabeth Head (E)

Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA.

Florence Lai (F)

Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.

H Diana Rosas (HD)

Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Massachusetts General Hospital, Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Charlestown, MA, USA.

William Klunk (W)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Bradley Christian (B)

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Timing of Alzheimer's Disease by Intellectual...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Timing of Alzheimer's Disease by Intellectual...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies chromosomiques › Syndrome de Down › Timing of Alzheimer's Disease by Intellectual...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Déficience intellectuelle › Timing of Alzheimer's Disease by Intellectual...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Timing of Alzheimer's Disease by Intellectual...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Timing of Alzheimer's Disease by Intellectual...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Timing of Alzheimer's Disease by Intellectual...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Timing of Alzheimer's Disease by Intellectual...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic radioisotopique › Scintigraphie › Tomoscintigraphie › Tomographie par émission de positons › Timing of Alzheimer's Disease by Intellectual...