Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The A4 study : β-amyloid and cognition in 4432 cognitively unimpaired adults

Insel, Philip S. LU ; Donohue, Michael C. ; Sperling, Reisa ; Hansson, Oskar LU orcid and Mattsson-Carlgren, Niklas LU orcid (2020) In Annals of Clinical and Translational Neurology 7(5). p.776-785
Abstract

Objective: To clarify the preclinical stage of Alzheimer’s disease by estimating when β-amyloid accumulation first becomes associated with changes in cognition. Methods: Here we studied a large group (N = 4432) of cognitively unimpaired individuals who were screened for inclusion in the A4 trial (age 65–85) to assess the effect of subthreshold levels of β-amyloid on cognition and to identify which cognitive domains first become affected. Results: β-amyloid accumulation was linked to significant cognitive dysfunction in cognitively unimpaired participants with subthreshold levels of β-amyloid in multiple measures of memory (Logical Memory Delayed Recall, P = 0.03; Free and Cued Selective Reminding Test, P < 0.001), the Preclinical... (More)

Objective: To clarify the preclinical stage of Alzheimer’s disease by estimating when β-amyloid accumulation first becomes associated with changes in cognition. Methods: Here we studied a large group (N = 4432) of cognitively unimpaired individuals who were screened for inclusion in the A4 trial (age 65–85) to assess the effect of subthreshold levels of β-amyloid on cognition and to identify which cognitive domains first become affected. Results: β-amyloid accumulation was linked to significant cognitive dysfunction in cognitively unimpaired participants with subthreshold levels of β-amyloid in multiple measures of memory (Logical Memory Delayed Recall, P = 0.03; Free and Cued Selective Reminding Test, P < 0.001), the Preclinical Alzheimer’s Cognitive Composite (P = 0.01), and was marginally associated with decreased executive function (Digit Symbol Substitution, P = 0.07). Significantly, decreased cognitive scores were associated with suprathreshold levels of β-amyloid, across all measures (P < 0.05). The Free and Cued Selective Reminding Test, a list recall memory test, appeared most sensitive to β-amyloid -related decreases in average cognitive scores, outperforming all other cognitive domains, including the narrative recall memory test, Logical Memory. Interpretation: Clinical trials for cognitively unimpaired β-amyloid-positive individuals will include a large number of individuals where mechanisms downstream from β-amyloid pathology are already activated. These findings have implications for primary and secondary prevention of Alzheimer’s disease.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of Clinical and Translational Neurology
volume
7
issue
5
pages
10 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:32315118
  • scopus:85083655992
ISSN
2328-9503
DOI
10.1002/acn3.51048
language
English
LU publication?
yes
id
d01ba6e0-9e6b-43bf-928a-e46909f523f3
date added to LUP
2020-05-28 11:44:06
date last changed
2024-09-19 22:40:18
@article{d01ba6e0-9e6b-43bf-928a-e46909f523f3,
  abstract     = {{<p>Objective: To clarify the preclinical stage of Alzheimer’s disease by estimating when β-amyloid accumulation first becomes associated with changes in cognition. Methods: Here we studied a large group (N = 4432) of cognitively unimpaired individuals who were screened for inclusion in the A4 trial (age 65–85) to assess the effect of subthreshold levels of β-amyloid on cognition and to identify which cognitive domains first become affected. Results: β-amyloid accumulation was linked to significant cognitive dysfunction in cognitively unimpaired participants with subthreshold levels of β-amyloid in multiple measures of memory (Logical Memory Delayed Recall, P = 0.03; Free and Cued Selective Reminding Test, P &lt; 0.001), the Preclinical Alzheimer’s Cognitive Composite (P = 0.01), and was marginally associated with decreased executive function (Digit Symbol Substitution, P = 0.07). Significantly, decreased cognitive scores were associated with suprathreshold levels of β-amyloid, across all measures (P &lt; 0.05). The Free and Cued Selective Reminding Test, a list recall memory test, appeared most sensitive to β-amyloid -related decreases in average cognitive scores, outperforming all other cognitive domains, including the narrative recall memory test, Logical Memory. Interpretation: Clinical trials for cognitively unimpaired β-amyloid-positive individuals will include a large number of individuals where mechanisms downstream from β-amyloid pathology are already activated. These findings have implications for primary and secondary prevention of Alzheimer’s disease.</p>}},
  author       = {{Insel, Philip S. and Donohue, Michael C. and Sperling, Reisa and Hansson, Oskar and Mattsson-Carlgren, Niklas}},
  issn         = {{2328-9503}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{776--785}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Annals of Clinical and Translational Neurology}},
  title        = {{The A4 study : β-amyloid and cognition in 4432 cognitively unimpaired adults}},
  url          = {{http://dx.doi.org/10.1002/acn3.51048}},
  doi          = {{10.1002/acn3.51048}},
  volume       = {{7}},
  year         = {{2020}},
}