Ontology highlight
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 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.
SUBMITTER: Insel PS
PROVIDER: S-EPMC7261742 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Insel Philip S PS Donohue Michael C MC Sperling Reisa R Hansson Oskar O Mattsson-Carlgren Niklas N
Annals of clinical and translational neurology 20200421 5
<h4>Objective</h4>To clarify the preclinical stage of Alzheimer's disease by estimating when β-amyloid accumulation first becomes associated with changes in cognition.<h4>Methods</h4>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.<h4>Results</h4>β-amyloid accumulation was lin ...[more]