Cognitive Function and Prevalence of Amyloid Marker in Frail Older Adults

Study Overview
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Brief Summary
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The current study seeks to examine the prevalence of amyloid pathology, among patients referred to the Toulouse Geriatric Frailty Clinic presenting objective memory impairment. We also aim to fully characterize the clinical progression of frail cognitively impaired patients presenting AD (Alzheimer Disease) pathology vs those who also present a cognitive impairment but do not have AD pathology.

Detailed Description
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The COGFRAIL study is a monocentric study integrating the longitudinal follow-up of 345 individuals referred to the Toulouse Frailty Clinic during 2 years. The procedure consists in neuroimaging to diagnose the presence of amyloid plaques in the brains and permit earlier detection of Alzheimer's disease. Visits will be scheduled at baseline, 1 and 2 years for a full neuropsychological, functional and physical evaluation. At 6 and 18 months patients will be seen in consultation by a Geriatrician and research assistant for a medical check. PET-Scan will be scheduled in the 2 months following inclusion for amyloid measurements. The MRI will be proposed, depending on the clinical relevance A blood sample for biobank will be taken at visit 2 and at the end of the study Extension study (CogFrail-Plus): The extension study will integrate an additional 2 years follow-up of the COGFRAIL study participants, following the initial 2 years period of the study: 2 Visits will be scheduled at 36 and 48 months for a full neuropsychological, functional and physical evaluation At 30 and 42 months patients will be seen in consultation by a Geriatrician and research assistant for a medical check A blood sample will be taken at 36 and 48 months.

Official Title
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Cognitive Function and Prevalence of Amyloid Marker in Frail Older Adults

Conditions
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Frail Elderly

Intervention / Treatment
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* Procedure: MRI and PET scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male individuals referred to the Toulouse Frailty Clinic with an objective memory impairment (CDR=0.5 or CDR=1) Age ≥ 70 years At least 1 Fried-criterion Informed consent signed by the patient Having an informant accompanying or available by phone Individuals affiliated to a healthcare scheme. - Willing to be informed in case of a new pathology discovered through medical examination Extension study (Cog-Frail Plus): COGFRAIL study participants still included in the study and completing their last visit (M 24) Having a family member or legal representant to sign the consent form if MMSE score <20 at the last visit (M24) Exclusion Criteria: Individuals presenting severe visual or auditory difficulties which may interfere with the completion of neuropsychological and functional assessments. Presence of any pathology or severe clinical or psychological condition that, according to the investigator, might interfere with study results or may expose the participants to additional risks. Individuals who are robust according to the Fried criteria (0 criteria) Individuals who are dependent (Activities of Daily Living (ADL) <4) Individuals who have a major deterioration in global cognitive function (Mini Mental State Examination (MMSE) <20) Subjects deprived of their liberty by administrative or judicial decision, or under guardianship or admitted to a healthcare or social institution (subjects in non-assisted living facilities could be recruited); Exclusion criteria for MRI scanning : Claustrophobia Trauma or surgery which may have left ferromagnetic material in the body, including pacemakers History of neurosurgery or aneurism Extension study (Cog-Frail Plus): Presence of any severe pathology that, according to the investigator, might interfere with study results or may expose the participants to additional risks. Subjects deprived of their liberty by administrative or judicial decision, or under guardianship

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: neuroimaging amyloid diagnosis by MRI and PET scan<br>There is only one arm. The procedure consists in neuroimaging to diagnose the presence of amyloid plaques in the brains and permit earlier detection of Alzheimer's disease. MRI and PET Scan. Visits at baseline, 1 and 2 years for a full neuropsychological, functional and physical evaluation. At 6 and 18 months in consultation by a Geriatrician and research assistant for a medical check. one PET-Scan in the 2 months following inclusion for amyloid measurements and one MRI, depending on the clinical relevance A blood sample for biobank at visit 2 and at visit 5. Extension study (CogFrail-Plus): additional 2 years follow-up of the COGFRAIL study participants, following the initial 2 years period of the study: 2 Visits at at 36 and 48 months for a full neuropsychological, functional and physical evaluation At 30 and 42 months in consultation by a Geriatrician and research assistant for a medical check A blood sample at 36 and 48 months. | Procedure: MRI and PET scan<br>* Neuroimaging with MRI and PET scan Amyloid tracer : For PET-scans, 4 MBq/kg of [18F]AV-45 will be injected into each subject in an intravenous bolus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amyloid physiological parameter | Amyloid pathology as corroborated with amyloid Positron Emission Tomography (PET) or lumbar punction | 2 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive function with Clinical Dementia Rating Scale (CDR) | Comparison between 2 timeframe to observe change in cognitive function between T12, T24 months | 12 and 24 months | 
| Changes in functional capacities with scales IADL | Changes in functional capacities, body composition, frailty phenotype, dietary intake and nutritional status with Instrumental Activities of Daily Living (IADL), Activities of Daily Living (ADL), Short Physical Performance Battery (SPPB). All measures analysed together, parameters are linked and must be evaluated all together to get the main information. | 12 and 24 months | 
| Changes in functional capacities with scales ADL | Changes in functional capacities, body composition, frailty phenotype, dietary intake and nutritional status with Instrumental Activities of Daily Living (IADL), Activities of Daily Living (ADL), Short Physical Performance Battery (SPPB). All measures analysed together, parameters are linked and must be evaluated all together to get the main information. | 12 and 24 months | 
| Changes in functional capacities with scales SPPB | Changes in functional capacities, body composition, frailty phenotype, dietary intake and nutritional status with Instrumental Activities of Daily Living (IADL), Activities of Daily Living (ADL), Short Physical Performance Battery (SPPB). All measures analysed together, parameters are linked and must be evaluated all together to get the main information. | 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive decline, frailty, mild cognitive impairment, Positron Emission Tomography, PET, Alzheimer disease, amyloid load, Magnetic resonance imaging, MRI