title: Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome.
abstract: Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-β deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-β deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels. There was a significant positive correlation (r = 0.62, P < 0.0001) between age and neocortical Pittsburgh compound B retention. This robust association makes it difficult to discriminate normative age-related decline in cognitive functioning from any potential effects of amyloid-β deposition. When controlling for chronological age in addition to mental age, there were no significant differences between the adults with Down syndrome who had elevated neocortical Pittsburgh compound B retention levels and those who did not on any of the neuropsychological measures. Similarly, when examining Pittsburgh compound B as a continuous variable, after controlling for mental age and chronological age, only the Rivermead Picture Recognition score was significantly negatively associated with neocortical Pittsburgh compound B retention. Our findings indicate that many adults with Down syndrome can tolerate amyloid-β deposition without deleterious effects on cognitive functioning. However, we may have obscured true effects of amyloid-β deposition by controlling for chronological age in our analyses. Moreover, our sample included adults with Down syndrome who were most 'resistant' to the effects of amyloid-β deposition, as adults already exhibiting clinical symptoms of dementia symptoms were excluded from the study.
authors.affiliation: 1 University of Wisconsin-Madison, Waisman Centre, 1500 Highland Ave, Madison, WI 53705, USA hartley@waisman.wisc.edu.
authors.forename: Sigan L
authors.initials: SL
authors.lastname: Hartley
authors.affiliation: 2 University of Pittsburgh, Department of Psychiatry, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Handen
authors.affiliation: 3 New York State Institute for Basic Research in Developmental Disabilities, 44 Holland Avenue, Albany, NY 12229, USA.
authors.forename: Darlynne A
authors.initials: DA
authors.lastname: Devenny
authors.affiliation: 4 University of Pittsburgh, Epidemiology Data Centre, 130 DeSoto Street, Pittsburgh, PA 15261, USA.
authors.forename: Regina
authors.initials: R
authors.lastname: Hardison
authors.affiliation: 1 University of Wisconsin-Madison, Waisman Centre, 1500 Highland Ave, Madison, WI 53705, USA.
authors.forename: Iulia
authors.initials: I
authors.lastname: Mihaila
authors.affiliation: 2 University of Pittsburgh, Department of Psychiatry, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
authors.affiliation: 2 University of Pittsburgh, Department of Psychiatry, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
authors.forename: Annie D
authors.initials: AD
authors.lastname: Cohen
authors.affiliation: 2 University of Pittsburgh, Department of Psychiatry, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: 1 University of Wisconsin-Madison, Waisman Centre, 1500 Highland Ave, Madison, WI 53705, USA.
authors.forename: Marsha R
authors.initials: MR
authors.lastname: Mailick
authors.affiliation: 1 University of Wisconsin-Madison, Waisman Centre, 1500 Highland Ave, Madison, WI 53705, USA.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: 1 University of Wisconsin-Madison, Waisman Centre, 1500 Highland Ave, Madison, WI 53705, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000814:Aniline Compounds / Q000008:administration & dosage; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D004314:Down Syndrome / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism / Q000503:physiopathology; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles / Q000008:administration & dosage
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles
keywords: Alzheimer’s disease; Down syndrome; PiB; amyloid; dementia