Cognitive composite score association with Alzheimer’s disease plaque and tangle pathology

Abstract

BackgroundCognitive composite scores are used as the primary outcome measures for Alzheimer’s disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target either amyloid or tau, we sought to establish an association between a cognitive composite score and the underlying pathology of AD.MethodsData from 192 older deceased and autopsied persons from the Rush Religious Order Study were used in this study. All participants were classified at their initial evaluations with a clinical diagnosis of no cognitive impairment (NCI). Of these individuals, 105 remained NCI at the time of their death while the remaining 87 progressed to mild cognitive impairment (MCI) or AD. A cognitive composite score composed of eight cognitive tests was used as the outcome measure. Individuals were classified into groups based on Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropathological diagnosis and Braak stage.ResultsThe rate of annualized composite score decline was significantly greater for the high CERAD (p < 0.001, d = 0.56) and Braak (p < 0.001, d = 0.55) groups compared with the low CERAD and Braak groups, respectively. Mixed-model repeated measure (MMRM) analyses revealed a significantly greater difference in composite score change from baseline for the high CERAD group relative to the low CERAD group after 5 years (Δ = −2.74, 95% confidence interval (CI) −5.01 to −0.47; p = 0.02). A similar analysis between low and high Braak stage groups found no significant difference in change from baseline (Δ = −0.69, 95% CI −3.03 to 1.66; p = 0.56).ConclusionsThese data provide evidence that decreased cognitive composite scores were significantly associated with increased AD pathology and provide support for the use of cognitive composite scores in AD prevention trials.

Associations between NIH Toolbox Cognition Battery and in vivo brain amyloid and tau pathology in non‐demented older adults

“…Traditional NP tests in common among the three neuroimaging studies include the Mini Mental State Exam (MMSE), Wechsler Memory Scale Revised (WMS‐R) Logical Memory Story A immediate and delayed recall, semantic fluency (animals), Trail Making Tests A & B, and clock drawing 29,30 . Traditional NP test data were analyzed as raw scores, with the exception of two standardized composite scores, a processing speed composite (comprising Trail Making Tests and semantic fluency), and a global composite (comprising all seven traditional NP variables), following published methods 31 …”

Analyzing large Alzheimer's disease cognitive datasets: Considerations and challenges

“…There is a recent surge in composites derived from batteries of tests in AD research 5 . They have been developed for multiple purposes, including sensitivity to global disease severity, 32 individual cognitive domains, 2,3 or longitudinal change 33 —particularly in the preclinical phase relevant to secondary prevention trials 34 . In their recent review, Schneider and Goldberg 5 identified 12 composite scales that have been used in clinical trials to assess cognitive functions.…”

Regional binding of tau and amyloid PET tracers in Down syndrome autopsy brain tissue

“…To confirm that the Tau tracers were binding to regions containing Tau, AT8 immunostaining was performed on adjacent sections at Barrow Neurological Institute. Paraffin-embedded sections were deparaffinized and pre-treated for antigen retrieval using formic acid, as previously described [ 12 ]. Endogenous peroxidase activity was blocked by 1% hydrogen peroxide, followed by incubation overnight with the AT8 monoclonal antibody (1:1000, Invitrogen).…”