Screening for predementia AD

Abstract

Objective: Data from the Einstein Aging Study (EAS) were used to prospectively evaluate the free recall score from the Free and Cued Selective Reminding Test (FCSRT-FR) and Logical Memory I immediate recall (LM-IR) subtest of the Wechsler Memory Scale-Revised for prediction of incident Alzheimer disease (AD) dementia among individuals from a community-based cohort with memory complaints.Methods: Analyses included 854 participants, age $70 years, who initially had no dementia, and had memory complaints. Clinic evaluations were completed annually and AD dementia was diagnosed using standard criteria (n 5 86 cases; average follow-up 4.1 years). Time-dependent receiver operating characteristic analysis was used to evaluate the prognostic ability of FCSRT-FR and LM-IR for incident AD over various durations of follow-up.Results: For identifying those with memory complaints who will develop incident AD dementia over 2-4 years, the FCSRT-FR had better operating characteristics than LM-IR. APOE e4 status, age, and education did not affect cut points; however, positive predictive values were higher among APOE e4-positive individuals.Conclusions: For follow-up intervals of 2-4 years, the FCSRT-FR is more predictive than the LM-IR for identifying individuals with memory complaints who will develop incident AD. APOE e4 status improves positive predictive value, but does not affect the choice of optimal cuts. Neurology Diagnostic guidelines for Alzheimer disease (AD) have been revised to reflect the view of the disease as a continuum.1,2 The long preclinical course of AD dementia suggests the potential for preventive measures aimed at the preclinical stages, and the search for biomarkers to identify asymptomatic individuals at high risk is underway. In the absence of definitive biomarkers to facilitate primary prevention, secondary prevention trials target persons without dementia with memory impairment and aim to delay or prevent onset of clinical AD dementia.1,2 A critical step in the design of these trials is the ability to discriminate between those with memory complaints attributable to underlying AD and those with impairment due to other causes. 325 There are different approaches to conceptualizing the symptomatic predementia phase of AD. Definitions of mild cognitive impairment (MCI) rely on norming cognitive performance relative to an age-and education-matched sample. However, if the goal is to identify individuals with high probability of developing AD dementia, the ideal cognitive cut scores for cognitive screening could be determined prospectively based on ability to predict incident AD dementia. Demographic and genetic covariates might enhance the predictive ability of these longitudinally derived screening cut scores. Because intervention studies may involve various

Early and late change on the preclinical Alzheimer's cognitive composite in clinically normal older individuals with elevated amyloid β

“…Separation of the Aβ+ group based on CDR progression revealed that Aβ-related PACC decline is predominantly driven by the subset of Aβ+ that progress on the CDR. This is not surprising, given that the selection of the PACC components was heavily influenced by studies examining decline associated with progression to MCI and dementia [33–35]. Although this finding provides confidence that PACC decline is associated with clinically relevant functional decline, it also suggests that PACC decline is honed for change that occurs relatively late in preclinical AD.…”

Variation in Variables that Predict Progression from MCI to AD Dementia over Duration of Follow-up

“…Derby et al (2013) applied time-dependent ROC analyses in the investigation of progression to AD dementia using data from the Einstein Aging Study (EAS), where they studied the predictive ability of a few cognitive measures and they assumed proportional hazards model for these measures. In our work, we considered measures from CSF and neuroimaging domains in addition to the cognitive domain and we found that additional measures did improve on the predictive utility of the cognitive measures.…”

The Preclinical Alzheimer Cognitive Composite

“…Previous studies 19–21 have reported evidence that both list learning and paragraph recall (measures of episodic memory) tend to decline 7 to 10 years prior to the diagnosis of MCI or Alzheimer dementia. Recent data from amyloid imaging studies 25–29 have reported a decline in multiple cognitive domains looking retrospectively at cognitive trajectories over 8 to 10 years prior to PET amyloid imaging 22–24 and prospectively over 1- to 3-year longitudinal follow-up.…”