Aging Stereotypes and Prodromal Alzheimer's Disease (AGING)

The Potential Impact of Aging Stereotypes in the Assessment of Memory Deficits and Screening for Prodromal State of Alzheimer's Disease

Because of the lengthening of life expectancy, more and more people are concerned with the effects of aging on their mental faculties (e.g., memory decline) and with the possibility of getting Alzheimer's Disease (AD) or other forms of dementia. This increasing awareness of AD has already resulted in a growing demand for neuropsychological testing. AD's research also emphasizes the need for early screening to improve the prediction of the disease progression and the efficacy of any future therapy. Such a drive to screen for pre-dementia raises the challenging issue of frontline identification of individuals in the preclinical or early clinical stages of AD. Mild Cognitive Impairment (MCI) is typically considered to be the prodromal state of AD, and is therefore at the core of the drive for early screening. Moreover, Pre-MCI so called SCI (Subjective Cognitive Impairment) can precede AD for 15 years. However, many individuals diagnosed with MCI do not convert to AD, some remaining stable and others even reversing back to normal (with rates of reversion to normal varying from 4.5% to as high as 53%). This over-diagnosis bias, which has been largely overlooked, is at the core of the present project at the interface of human and life sciences. Here, we argue that an important source of overdiagnosis in the prodromal state of AD comes from negative aging stereotypes (e.g., the culturally shared beliefs that aging inescapably causes severe cognitive decline and diseases such as AD) that permeate neuropsychological screening. There is ample evidence in the laboratory that such stereotypes contribute to the differences observed in the healthy population between younger and older adults in explicit memory tasks. Additionally, three pilot (lab) studies specifically conducted for the present ANR project showed that the threat of being judged stereotypically undermines the controlled use of memory of healthy older adults and simultaneously intensifies their automatic response tendencies, resulting in impaired memory performance. The present proposal goes several steps further by examining for the first time whether aging stereotypes are powerful enough to implicitly permeate the clinical neuropsychological testing and thus inflate memory deficits in older adults judged "at risk" (based on either epidemiological criteria or memory complaints), resulting in false-positive detection of SCI and MCI. This provocative hypothesis will be tested while 1) using biomarkers of neurodegeneration to distinguish false-positives from true MCI, and 2) using biomarkers of stress to examine whether and how aging stereotypes can lead to acute physiological stress during neuropsychological testing. This innovative project has the potential to offer new recommendations to improve the diagnosis accuracy of prodromal state of AD, with positive consequences for older people's wellbeing.

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment (MCI)
• Intervention / Treatment: Diagnostic test: Diagnosis of MCI versus No MCI (SCI or healthy patient); Diagnostic test: Diagnosis of MCI versus No MCI (SCI or healthy patient)

• Study Type: Interventional
• Enrollment (Anticipated): 260
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bernard MICHEL, PH; Phone Number: +33 491744675; Email: bmichel@ap-hm.fr
• Study Contact Backup: Name: Isabelle REGNER, PhD; Phone Number: +33 413550993; Email: isabelle.regner@univ-amu.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Contact: Bernard MICHEL, PH; Phone Number: +33 491744675; Email: bmichel@ap-hm.fr
    • Principal Investigator: Bernard MICHEL, PH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be at least 50 years old
• Patients must report memory complaints
• Patients must show signs of MCI (amnestic single or multiple domain) on the following short cognitive tests

Exclusion Criteria:

• Probable Alzheimer's Disease according to NINCDS-ADRDA criteria (MA patients will be excluded from the study because false-positive errors only concern MCI status, not AD)
• Psychiatric disorders (schizophrenia, bipolar disorder)
• Cranial trauma
• Developmental pathologies
• Depression (score greater than or equal to 10 on GDS)
• Psychotropic medication if modified in the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard instruction	Diagnostic test: Diagnosis of MCI versus No MCI (SCI or healthy patient); Neuropsychological tests; Diagnostic test: Diagnosis of MCI versus No MCI (SCI or healthy patient); Neuroimaging biomarkers of neurodegeneration
Experimental: Reduced threat instruction	Diagnostic test: Diagnosis of MCI versus No MCI (SCI or healthy patient); Neuropsychological tests; Diagnostic test: Diagnosis of MCI versus No MCI (SCI or healthy patient); Neuroimaging biomarkers of neurodegeneration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological tests	Neuropsychological battery used for the diagnosis of Mild Cognitive Impairment (MCI, amnestic single or multiple domain)	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroimaging biomarkers of neurodegeneration	Structural MRI (Hippocamp) and Florbetapir© PET (β-amyloid deposition)	48 months
Physiological stress	cortisol, dehydroepiandrosterone (DHEA) and its sulfated stable form (DHEAS) from the HPA axis, and Immunoglobulin A (IgA).	48 months
Self-report questionnaires	Vulnerability factors for stereotyping threat effects are assessed	48 months
Heart rate variability (thin elasticized heart rate transmitter belt),	Physiological stress	48 months
Skin conductance (wristwatch)	Physiological stress	48 months
Salivary biomarkers	cortisol, dehydroepiandrosterone (DHEA) and its sulfated stable form (DHEAS) from the HPA axis, and Immunoglobulin A (IgA).	48 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Publications and helpful links

General Publications

• Gauthier K, Morand A, Dutheil F, Alescio-Lautier B, Boucraut J, Clarys D, Eustache F, Girard N, Guedj E, Mazerolle M, Paccalin M, de la Sayette V, Zarea A, Huguet P, Michel BF, Desgranges B; AGING consortium, Regner I. Ageing stereotypes and prodromal Alzheimer's disease (AGING): study protocol for an ongoing randomised clinical study. BMJ Open. 2019 Oct 7;9(10):e032265. doi: 10.1136/bmjopen-2019-032265.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2018
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: April 10, 2017
• First Submitted That Met QC Criteria: April 28, 2017
• First Posted (Actual): May 3, 2017

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: 2016-45; IDRCB Number (Other Identifier: 2017-A00946-47)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No