Religious Orders Study and Memory and Aging Project (ROS/MAP)

Introduction

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The Religious Orders Study (ROS) and Memory and Aging Project (MAP) are two landmark longitudinal cohort studies of aging and cognitive decline. Conducted by researchers at Rush University, these studies have generated foundational data on the neuropathology, risk factors, and biomarkers of Alzheimer’s Disease and related dementias.

Study Design

Religious Orders Study (ROS)

The Religious Orders Study began in 1994 with:^{1[Hirsutism and hypertrichosis in adults: investigations and treatment].2002 · Annales de dermatologie et de venereologie · PMID 12223963Open reference}

• Participants: Catholic nuns, monks, and brothers

• Enrollment: Over 1,100 participants

• Age at enrollment: 65+ years

• Annual assessments: Comprehensive cognitive testing

Memory and Aging Project (MAP)

Launched in 1997, MAP includes:^{2Missed Monteggia injuries.2006 · Injury · DOI 10.1016/j.injury.2004.12.033 · PMID 16214464Open reference}

• Participants: Community-dwelling adults

• Enrollment: Over 1,600 participants

• Age at enrollment: 55+ years

• Annual assessments: Same protocol as ROS

Unified Protocol

Both studies use identical:^{3Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes.2016 · Lancet (London, England) · DOI 10.1016/S0140-6736(15)60806-6 · PMID 26313057Open reference}

• Cognitive test batteries

• Food frequency questionnaires

• Clinical assessments

• Brain donation protocols

Data Collection

Cognitive Testing

Annual assessments include:^{4Ensembl 2014.2014 · Nucleic acids research · DOI 10.1093/nar/gkt1196 · PMID 24316576Open reference}

• Episodic memory: Word list recall, story recall

• Executive function: Trail making, digit ordering

• Semantic memory: Category fluency

• Perceptual speed: Symbol comparison

• Visuospatial ability: Visual reproduction

Clinical Assessments

• Diagnoses: NINCDS-ADRDA, NINDS AIREN criteria

• Dementia staging: Clinical Dementia Rating

• Functional assessment: Activities of daily living

• Psychiatric evaluation: Depression screening

Brain Donation

A unique strength: Nearly all participants consent to brain donation, enabling:^{5The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study.2022 · The Lancet. Neurology · DOI 10.1016/S1474-4422(22)00208-3 · PMID 35841910Open reference}

• Neuropathologic assessment

• Correlation with antemortem data

• Validation of biomarker studies

Major Findings

Neuropathology of AD

ROS/MAP revealed that:^{6Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial.2020 · Lancet (London, England) · DOI 10.1016/S0140-6736(19)32500-0 · PMID 31862249Open reference}

• Mixed pathology is common

• Tangles predict cognitive decline

• Amyloid modulates effects

Mixed Pathology

Studies demonstrate:^{7Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.2017 · Endoscopy · DOI 10.1055/s-0042-108641 · PMID 27299638Open reference}

• Co-occurrence of multiple pathologies

• TDP-43 in aging

• Impact on clinical expression

LATE

The studies identified:^{8Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.2018 · Movement disorders : official journal of the Movement Disorder Society · DOI 10.1002/mds.26987 · PMID 28467028Open reference}

• Limbic predominant age-related TDP-43 encephalopathy (LATE)

• New pathologic entity

• Clinical significance

APOE Effects

APOE4 carriers show:^{9PATROL: Participatory Activity Tracking and Risk Assessment for Anonymous Elderly Monitoring.2022 · Sensors (Basel, Switzerland) · DOI 10.3390/s22186965 · PMID 36146314Open reference}

• Increased amyloid accumulation

• Interaction with other pathologies

• Faster cognitive decline

Cognitive Reserve

Higher education and religious participation:^{10Electroencephalogram Based Detection of Deep Sedation in ICU Patients Using Atomic Decomposition.2019 · IEEE transactions on bio-medical engineering · DOI 10.1109/TBME.2018.2813265 · PMID 29993386Open reference}

-buffers against pathology

• Slower cognitive decline

• Delayed clinical onset

Biomarkers

ROS/MAP biomarker studies:^{2Missed Monteggia injuries.2006 · Injury · DOI 10.1016/j.injury.2004.12.033 · PMID 16214464Open reference}0

• Plasma neurofilament light chain

• CSF tau and Abeta

• Imaging biomarkers

Genetics

Genomic studies identified:^{2Missed Monteggia injuries.2006 · Injury · DOI 10.1016/j.injury.2004.12.033 · PMID 16214464Open reference}1

• Novel AD risk loci

• Expression quantitative trait loci

• Functional mechanisms

Cohorts and Substudies

Minority Recruitment

• Minority Aging Project (MAP-R)

• African American participants

• Comparable assessments

Clinical Subsamples

• MRI substudy

• CSF substudy

• Autopsy substudy

Impact on the Field

Standards

ROS/MAP established:^{2Missed Monteggia injuries.2006 · Injury · DOI 10.1016/j.injury.2004.12.033 · PMID 16214464Open reference}2

• Cognitive test batteries for aging

• Neuropathologic protocols

• Data sharing frameworks

Biomarker Validation

Studies validated:

• CSF biomarkers

• Plasma biomarkers

• Neuroimaging markers

Drug Development

Data support:

• Target validation

• Clinical trial design

• Patient stratification

Data Access

Data are publicly available:^{2Missed Monteggia injuries.2006 · Injury · DOI 10.1016/j.injury.2004.12.033 · PMID 16214464Open reference}3

• ROS/MAP website: https://www.radcstudy.org

• National Archive: NIAGADS

• Access application: Required

Cross-Links to Related Pages

Related Diseases

• Alzheimer’s Disease

• Mild Cognitive Impairment

• Frontotemporal Dementia

Related Genes

• APOE

Related Mechanisms

• Neurofibrillary Tangles

• Amyloid Plaques

• TDP-43 Proteinopathy

Related Biomarkers

• CSF Biomarkers

• Amyloid Beta

• Tau Proteins

Related Datasets

• UK Biobank

• ADNI

External Links

• ROS/MAP Official Website

• Rush Alzheimer’s Disease Center

• National Institute on Aging