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Investigation of AlzHeimer's Predictors in Subjective Memory Complainers - Extension Study

Not Applicable
Recruiting
Conditions
Memory Complaint
Memory Disorders
Alzheimer Disease
Interventions
Procedure: Electroencephalogram (EEG)
Procedure: Oculomotor tests
Procedure: MRI
Radiation: 18-F amyloid PET Scan
Radiation: 18F-fluorodeoxyglucose (FDG) PET Scan
Biological: Blood sampling
Biological: Lumbar puncture
Registration Number
NCT05806697
Lead Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Brief Summary

A regional, single-center, prospective, observational academic cohort will follow subjects who previously participated in the INSIGHT study and who agree an extension of their follow-up in the INSIGHT-2 research for additional 5-6 years. An annual multimodal evaluation (cognitive, oculomotor, biological and neuroimaging) will be proposed in order to describe the natural history of preclinical Alzheimer's disease (AD). The primary endpoint is the conversion to the symptomatic stage in subjects at risk, identified by positive amyloid staining (A+) on florbetapir positron emission tomography (PET) imaging. The size of the cohort is estimated to around 240 participants (61 A+ subjects) among the 318 participants included in the main cohort (88 A+ subjects). The follow-up in the INSIGHT-2 cohort will be lightened compared to that of the main cohort with an annual frequency of visits rather than a six-monthly one.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
240
Inclusion Criteria
  • Subjects that previously participated in the INSIGHT cohort
  • Aged 70 to 95 years old
  • Having signed an informed consent
  • Willing to and able undergo a baseline PET amyloid imaging
  • Affiliating to the French health-care system
  • Having an identified informant who has sufficient contact with the participant and has to be able to provide accurate information, at least by phone, about the participants' cognitive and functional abilities.
Exclusion Criteria
  • Clinical Dementia Rating ≥1 at screening/baseline visit only
  • Fulfilling research diagnostic criteria for any type of dementia-related disorder at screening visit (clinical AD, Dementia with Lewy Bodies [DLB], fronto-temporal dementia [FTD], vascular dementia, chronic traumatic encephalopathy [CTE], Limbic-predominant Age-related TDP-43 Encephalopathy [LATE], Primary age-related tauopathy [PART)
  • Presence of any medical condition associated with a long-term risk of cognitive impairment or dementia including Parkinson's disease, brain tumor, subdural hematoma, vascular malformations, territorial stroke (excluding smaller watershed strokes), chronic hydrocephalus, traumatic brain injury with neurological sequelae, active alcohol/drug abuse, major depressive disorder, schizophrenia and bipolar disorder
  • Current serious or unstable illnesses (including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic or hematologic disease) that might make the subject's participation in an investigational trial unsafe
  • Any contraindications for MRI/ PET scan procedure (claustrophobia, ferromagnetic object in the body), to FDG or to 18F-Florbetapir (Amyvid®).
  • Hypersensitivity to the active substance or to any of the excipients of 18F-Florbetapir (Amyvid®).
  • Participation in any clinical trial of an investigational product in the last 30 days before the screening (during all study duration co-inclusion in other clinical trial of an investigational product or observational research [biomarker cohort e.g.] will be possible but the information would need to be recorded).
  • Unable to comply with protocol requirements in the opinion of the investigator
  • Being under guardianship (safeguard of justice, curatorship or guardianship)
  • Residence in skilled nursing facility, including nursing homes (EHPAD).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
All participantsMRI-
All participantsBlood sampling-
All participantsOculomotor tests-
All participants18F-fluorodeoxyglucose (FDG) PET Scan-
All participantsElectroencephalogram (EEG)-
All participantsLumbar puncture-
All participants18-F amyloid PET Scan-
Primary Outcome Measures
NameTimeMethod
The primary endpoint is the conversion to typical AD during the 5-year follow-up.every year through study completion, from baseline for 5 years (M60)

Typical AD according to International Working Group (IWG) 2014 criteria = amyloid-positive participants, with an abnormal decline of episodic memory performance on the Free and Cued Selective Reminding Test

Secondary Outcome Measures
NameTimeMethod
Change of the score in different self-administered, informant based questionnaires (including the Quality Of Life (QOL), Ascertain Dementia 8 (AD)8 Dementia Screening Interview, Aging Brain Care Monitor)Each 1 year from baseline for 5 years (M60)

Exploratory outcomes

Conversion to symptomatic non-AD cognitive diseaseEach 1 year from baseline for 5 years (M60)

Atypical AD according to IWG 2014 criteria

Diagnosis of cerebral amyloid angiopathy based on V2.0 BOSTON criteriaEach 1 year from baseline for 5 years (M60)

As described in the following reference: Charidimou et al., Lancet Neurol. 2022 Aug;21(8):714-725

Rate of change in biomarkers measured from blood, CSF, structural and functional neuroimaging (MRI), EEG and molecular neuroimaging (18F-FDG-PET and amyloid imaging)Each 1 year from baseline for 5 years (M60)

Exploratory outcomes

Change in Clinical Dementia Rating- Sum of Boxes (CDR-SB) score compared to baselineEach 1 year from baseline for 5 years (M60)

CDR-SB : Hughes, Br J Psychiatry 1982; 140: 566-72

Change in different neuroimaging, biological, electrophysiological and oculomotor parameters compared to baselineEach 1 year from baseline for 5 years (M60)

Exploratory outcomes

Trial Locations

Locations (1)

Hôpital Pitié Salpêtrière

🇫🇷

Paris, Ile de france, France

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