The Wisconsin Registry for Alzheimer's Prevention: A review of findings and current directions

Abstract

The Wisconsin Registry for Alzheimer's Prevention is a longitudinal observational cohort study enriched with persons with a parental history (PH) of probable Alzheimer's disease (AD) dementia. Since late 2001, Wisconsin Registry for Alzheimer's Prevention has enrolled 1561 people at a mean baseline age of 54 years. Participants return for a second visit 4 years after baseline, and subsequent visits occur every 2 years. Eighty-one percent (1270) of participants remain active in the study at a current mean age of 64 and 9 years of follow-up. Serially assessed cognition, self-reported medical and lifestyle histories (e.g., diet, physical and cognitive activity, sleep, and mood), laboratory tests, genetics, and linked studies comprising molecular imaging, structural imaging, and cerebrospinal fluid data have yielded many important findings. In this cohort, PH of probable AD is associated with 46% apolipoprotein E ( APOE ) ε4 positivity, more than twice the rate of 22% among persons without PH. Subclinical or worse cognitive decline relative to internal normative data has been observed in 17.6% of the cohort. Twenty-eight percent exhibit amyloid and/or tau positivity. Biomarker elevations, but not APOE or PH status, are associated with cognitive decline. Salutary health and lifestyle factors are associated with better cognition and brain structure and lower AD pathophysiologic burden. Of paramount importance is establishing the amyloid and tau AD endophenotypes to which cognitive outcomes can be linked. Such data will provide new knowledge on the early temporal course of AD pathophysiology and inform the design of secondary prevention clinical trials.

Measuring longitudinal cognition: Individual tests versus composites

“…Participants in WRAP complete a comprehensive cognitive battery described in full elsewhere [5]. Cognitive tests incorporated in the current analyses include the Rey Auditory‐Verbal Learning Test (AVLT) [15]; the Logical Memory subtest of the Wechsler Memory Scale—Revised (LM) [16]; the Brief Visuospatial Memory Test—Revised (BVMT) [17]; the Stroop test, Color–Word Interference (STROOP) [18]; the Trail Making Test, parts A and B (TMT‐A and TMT‐B) [19]; the Digit Symbol subtest of the Wechsler Adult Intelligence Scale—Revised (DIGSYM) [20]; the Controlled Oral Word Association Test, CFL version (CFL) [21]; and the Mini‐Mental State Exam (MMSE) [22].…”

“…To understand variability across tests and time, longitudinal studies of cognition typically include comprehensive cognitive batteries assessing many domains [5,6]. Separate analysis of each outcome without considering familywise type I error risks spurious or irreproducible findings [7].…”

Speech databases for mental disorders: A systematic review

“…The Distress Analysis Interview Corpus-Wizard of Oz (DAIC-WOZ) database is part of a larger corpus, the DAIC, which contains both audio and video recordings of patients with anxiety, depression and post-traumatic stress disorder (PTSD) 19. Finally, the Wisconsin Registry for Alzheimer’s Prevention (WRAP) 20is a longitudinal study containing recordings and transcriptions of 264 participants (200 cognitively healthy and 64 with early mild cognitive impairment [MCI]). It was developed for determining if participants with very early, subclinical memory declines were connected with declines in their language.…”

Characterizing the Effects of Sex, APOE ɛ4, and Literacy on Mid-life Cognitive Trajectories: Application of Information-Theoretic Model Averaging and Multi-model Inference Techniques to the Wisconsin Registry for Alzheimer’s Prevention Study

“…WRAP is a longitudinal cohort study enriched for AD-risk via over-enrollment of participants with a parental history of AD (for details, see (Johnson et al, 2017)); primary aims of the study include identifying predictors associated with cognitive decline and estimating their associations. All participants were free of dementia at baseline.…”

“…The first follow-up visit occurred approximately 4 years after baseline, with subsequent visits occurring approximately every 2 years (for details, see (Johnson et al, 2017)). We analyze ten outcomes in this study that have been shown to be sensitive to AD-related cognitive changes (one intraindividual variability (IICV) measure and nine cognitive measures available since baseline of the WRAP study).…”