The A4 study : β-amyloid and cognition in 4432 cognitively unimpaired adults
Insel, Philip S. LU ; Donohue, Michael C. ; Sperling, Reisa ; Hansson, Oskar LU
and Mattsson-Carlgren, Niklas
LU
(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)
- author
- Insel, Philip S.
LU
; Donohue, Michael C.
; Sperling, Reisa
; Hansson, Oskar
LU
and Mattsson-Carlgren, Niklas
LU
- organization
- publishing date
- 2020-05
- 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 < 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.</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}},
}