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

Sigan L Hartley; Victoria Fleming; Emily K Schworer; Jamie Peven; Benjamin L Handen; Sharon Krinsky-McHale; Christy Hom; Laisze Lee; Dana L Tudorascu; Charles Laymon; Davneet Minhas; Weiquan Luo; Annie Cohen; Shahid Zaman; Beau M Ances; Mark Mapstone; Elizabeth Head; Florence Lai; H Diana Rosas; William Klunk; Bradley Christian; Alzheimer Biomarker Consortium-Down Syndrome

doi:10.3233/JAD-230200

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

J Alzheimers Dis. 2023;95(1):213-225. doi: 10.3233/JAD-230200.

Authors

Sigan L Hartley^{1

2}, Victoria Fleming^{1

2}, Emily K Schworer¹, Jamie Peven³, Benjamin L Handen³, Sharon Krinsky-McHale⁴, Christy Hom⁵, Laisze Lee³, Dana L Tudorascu³, Charles Laymon⁶, Davneet Minhas⁶, Weiquan Luo⁶, Annie Cohen³, Shahid Zaman^{7

8}, Beau M Ances⁹, Mark Mapstone¹⁰, Elizabeth Head¹¹, Florence Lai¹², H Diana Rosas^{12

13}, William Klunk³, Bradley Christian¹; Alzheimer Biomarker Consortium-Down Syndrome

Affiliations

¹ Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
² School of Human Ecology, University of Wisconsin-Madison, Madison, WI, USA.
³ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Department of Psychology, New York Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
⁵ Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
⁶ Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ Cambridgeshire & Peterborough NHS Foundation Trust (CPFT), Elizabeth House, Fulbourn Hospital, Cambridge, UK.
⁸ Department of Psychiatry, Cambridge Intellectual & Developmental Disabilities Research Group (CIDDRG), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
⁹ Department of Neurology, Washington University St. Louis, St. Louis, MO, USA.
¹⁰ Clinical Neurology, University of California, Irvine, Irvine, CA, USA.
¹¹ Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA.
¹² Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
¹³ Massachusetts General Hospital, Center for Neuro-imaging of Aging and Neurodegenerative Diseases, Charlestown, MA, USA.

Abstract

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.

Keywords: Alzheimer’s disease; Down syndrome; amyloid; cognitive; dementia; imaging; intellectual; memory; tau.

Publication types

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

MeSH terms

Adult
Age of Onset
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / etiology
Alzheimer Disease* / metabolism
Amyloid beta-Peptides / metabolism
Apolipoprotein E4* / metabolism
Biomarkers / metabolism
Cross-Sectional Studies
Down Syndrome* / complications
Down Syndrome* / diagnostic imaging
Down Syndrome* / psychology
Female
Humans
Intellectual Disability* / diagnosis
Intellectual Disability* / diagnostic imaging
Intellectual Disability* / metabolism
Male
Middle Aged
Positron-Emission Tomography
Time
tau Proteins* / metabolism

Substances

Amyloid beta-Peptides
tau Proteins
Apolipoprotein E4
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding