The Wisconsin Registry for Alzheimer’s Prevention: A Review of findings and current directions

Abstract

The Wisconsin Registry for Alzheimer's Prevention (WRAP) is a longitudinal observational cohort study enriched with persons with a parental history (PH) of probable Alzheimer's Disease (AD) dementia. Since late 2001, WRAP has enrolled 1,561 people at a mean baseline age of 54. Participants return for a second visit four years after baseline and subsequent visits occur every two 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% APOE e4 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.

Declines in Connected Language Are Associated with Very Early Mild Cognitive Impairment: Results from the Wisconsin Registry for Alzheimer’s Prevention

“…The WRAP is a longitudinal study of late-middle-aged adults enriched for AD risk based on parental family history. WRAP participants are asymptomatic, English speaking, and are between the ages of 40 and 65 at the time of enrollment ( Sager et al, 2005 ; Johnson et al, 2017 ). Approximately 72% of participants have a parent with either autopsy-confirmed or probable AD [family history positive (FH+)] as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s disease and Related Disorders Association (NINCDS-ADRDA) criteria ( McKhann et al, 1984 ).…”

“…The main component of this experimental diagnosis is a subtle cognitive deficit less pronounced than the traditional MCI diagnosis and not requiring a cognitive complaint from the participant or informant, (3) clinical MCI, (4) clinical impairment-not MCI, or (5) dementia. For additional detailed information on the consensus diagnosis process, see Koscik et al (2016) and Johnson et al (2017) . Because the aim of this study was to capture language problems very early on in the possible-AD continuum, we excluded participants who were diagnosed with dementia, clinical MCI or “clinical impairment-not MCI” ( n = 9).…”

Brain Glucose Metabolism, Cognition, and Cardiorespiratory Fitness Following Exercise Training in Adults at Risk for Alzheimer’s Disease

“…Twenty-three asymptomatic, late-middle-aged adults were included in this pilot randomized, controlled, 26-week aerobic exercise training intervention. Participants were recruited from the Wisconsin Registry for Alzheimer's Prevention (WRAP), a cohort enriched for family history of AD and the APOE 4 allele [21], or the Wisconsin Alzheimer's Disease Research Center (WADRC) Investigating Memory in People At risk, Causes and Treatments (IMPACT) cohort. Thirty-eight (WRAP) to 40% (WADRC IMPACT) of participants in these cohorts carry at least one APOE 4 allele as compared to approximately 15% in a population of comparable age [22].…”

“…Weight was measured to the nearest tenth of a kilogram using a medical grade scale and height was measured using a stadiometer. All participants already had parental history of AD and APOE genetic status on record [21]. Fasting blood samples were collected from the antecubital vein and sent to the UW Health Central Laboratory for analysis of clinical laboratory values.…”

Protocol of Aerobic Exercise and Cognitive Health (REACH): A Pilot Study

“…IMPACT stood at 79% white, 57 years of age, 66% female, 55% with parental history of AD, 38% carrying at least one APOE 4 allele, and a mean of 16 years of schooling. Further details about the WRAP cohort have been previously published [28]. Parental history of AD was determined by either neuropathological confirmation, diagnosis by a physician, review of medical records, or by evaluation using the Dementia Questionnaire [29].…”