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.
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
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
Single group
Electroencephalogram (EEG)
Procedure/SurgeryThe EEG will be uniquely performed during for the whole study if a given subject converts to symptomatic AD or in the occurrence of significant cognitive decline.
Oculomotor tests
Procedure/SurgeryAll participants in the INSIGHT-2 study are invited to perform the oculomotor test, excepting subjects reporting oculomotor disorders.
MRI
Procedure/SurgeryAll INSIGHT-2 participants will undergo a baseline MRI (structural and resting state fMRI) a follow-up MRI at M12, M36 and M60.
18-F amyloid PET Scan
RadiationThe primary endpoint is conversion to the symptomatic stage in subjects at risk, identified by positive amyloid staining (A+) on florbetapir PET imaging. Participants will receive an injection of 18F-Florbetapir prior to undergoing amyloid PET scanning. Florbetapir (18F) is an experimental imaging compound labeled with \[18F\] fluorine that decays by positron (β+) emission and has a half-life of 109.77 min. This procedure will be done at baseline.
18F-fluorodeoxyglucose (FDG) PET Scan
RadiationParticipants will receive an injection of Fludeoxyglucose 18F prior to undergoing FDG-PET. The \[18F\]FDG is the most well-known radiopharmaceutical positron emitter, in both clinical and preclinical fields.
Blood sampling
Biological/VaccineA total of 80 ml of whole blood will be collected for each participant in the INSIGHT-2 study for routine laboratory assessment and biobank sampling.
Lumbar puncture
Biological/VaccineA lumbar puncture for cerebrospinal fluid (CSF) collection is proposed to all participants.
The primary endpoint is the conversion to typical AD during the 5-year follow-up.
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
Change in Clinical Dementia Rating- Sum of Boxes (CDR-SB) score compared to baseline
CDR-SB : Hughes, Br J Psychiatry 1982; 140: 566-72
Change in different neuroimaging, biological, electrophysiological and oculomotor parameters compared to baseline
Exploratory outcomes
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)
Exploratory outcomes
Rate of change in biomarkers measured from blood, CSF, structural and functional neuroimaging (MRI), EEG and molecular neuroimaging (18F-FDG-PET and amyloid imaging)
Exploratory outcomes
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