Influence of Age on Amyloid Load in Alzheimer's Disease and in Atypical Focal Cortical Alzheimer's Disease (BIOMAGE)

Influence of Age on amyloïd Load in Alzheimer's Disease and in Atypical Focal Cortical Alzheimer's Disease Like Posterior Cortical Atrophy (PCA) and Logopenic Progressive Aphasia (LPA)Using Positron Emitting Tomography (PET) Imaging

The first objective is to asses influence of age on amyloid load measured by PET imaging using Pittsburgh B compound (PiB) radio-tracer, in Alzheimer's disease(AD). This will allow the determination of brains age-specific deterioration factors by comparing Early onset AD (EOAD), Late onset AD (LOAD)and atypical focal cortical AD (PCA and LPA). The amount of brain lesions in AD patients is estimated by:

1. measuring the rate of cortical brain atrophy,
2. FDG imaging of glucose metabolism reflecting neuronal activity, and
3. for patients who benefited from a lumbar puncture; Cortical-spinal fluid (CSF) amounts of amyloïd and tau proteins are measured.

Study Overview

• Status: Completed
• Conditions: Logopenic Progressive Aphasia; Posterior Cortical Atrophy; Alzheimer's Disease

Detailed Description

Literature data suggests there are different types of AD depending on their age of onset, called EOAD and LOAD. These two categories are distinguished by the localization of brain atrophy : severe and 'posterior' in EOAD and more 'anterior' in LOAD. Neuro-pathologic data suggests some atypical focal cortical atrophy, characterized by a respect of episodic memory, may be classified within EOAD.

PiB-based PET imaging allows the in-vivo visualization and quantification of amyloïd load.

We want to answer the question whether the amount of amyloïd protein may be lower in LOAD than EOAD in patients showing the same level of dementia, and thus identify ageing-specific cognitive disorders and understand witch factors influence etio-pathology of typical and atypical Alzheimer's disease.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Ile de France
    • Paris, Ile de France, France, 75651
      • Pitié Salpétrière Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients have to fulfil criteria for (1)AD with an amnesic syndrome of the media-temporal type, EOAD have lower frequency and (2) and for atypical Ad respecting episodic memory, inaugural language disorder or visual-spatial disorder

Description

Inclusion Criteria:

• AD patients: clinical dementia rating between 0.5 and 2 free and cued recall test (Grober and Buschke) cued-recall < 18/48 and total recall < 40/48
• atypical AD : i visual-spatial disorder and respect of episodic memory progressive evolution, Balint syndrome ii progressive language disorder constituted of logopenic aphasia respect of episodic memory
• controls: age over 30 MMSE over or equal to 27 normal neuropsychiatric state for age and education level

Exclusion Criteria:

• for every patients : psychiatric disorders age under18 absence of social security counter indication to MRI supposed or actual alcoholism or drug addiction pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
EOAD typical AD; this cohort is constituted with early onset typical AD.
LOAD typical; this group is constituted with late onset typical AD
atypical AD; this group is constituted with atypical form of focal cortical atrophy, like posterior cortical atrophy and logopenic progressive aphasia.
young controls; under 65
old controls; over 65

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PIB-PET imaging of amyloid load	PET imaging using PIB radio-tracer will give an estimation of regional amyloid load for every patient	0 - 2 months
FDG-PET imaging of glucose metabolism	PET imaging using 18F-fluorodesoxyglucose (FDG) will give a visualization of regional neuronal metabolism	0 - 2 months
clinical phenotypic assessment	the clinical evaluation includes a neurologic consulting, a neuropsychologic assessment of cognitive performances, and evaluation of autonomy	0 - 2 months
MRI	the magnetic resonance imaging will be performed using numerous modalities like T1 weighted sequences for anatomic information, T2 weighted FLAIR and TSE sequences to avoid vascular injuries and T2 GRE to avoid microbleeds, DTI for the diffusion tensor imaging and default mode FMRI, to identify neural networks involved in default concious mode.	0 - 2 months
ApoE gene sequencing	ApoE gene sequencing, will be performed after all samples have been collected. So this may be 0 to 24 month after inclusion.	0 - 24 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
amyloid and Tau measurements in cerebro-spinal fluid (csf)	some patients have a lumbar puncture that allows a direct quantification of CSF amyloid, tau and phospho-tau amounts.This measure is performed in the 6 months following the clinical assessment (at inclusion) and when a former puncture has already been done, it can be used retro-actively up to 6 months before clinical assessment.	-6 months or +6months arround T0

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Bruno Dubois, professor doctor, Inserm U975; Study Chair: marie c sarzin, doctor, Inserm U975

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: March 12, 2010
• First Submitted That Met QC Criteria: March 29, 2010
• First Posted (Estimate): March 30, 2010

Study Record Updates

• Last Update Posted (Estimate): October 10, 2012
• Last Update Submitted That Met QC Criteria: October 8, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Alzheimer's disease; brain atrophy; cognitive impairment; Pet imaging; amyloid protein; PIB imaging,
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Dementia; Tauopathies; Language Disorders; Communication Disorders; Speech Disorders; Alzheimer Disease; Atrophy; Aphasia
• Other Study ID Numbers: C08-30; 2008-A00939-46 (Registry Identifier: IDRCB)