Study protocol on Alzheimer's disease and related disorders: focus on clinical and imaging predictive markers in co-existing lesions

Nawele Boublay, Denis Fédérico, Alain Pesce, Marc Verny, Frédéric Blanc, Marc Paccalin, Thomas Desmidt, Pierre Grosmaître, Olivier Moreaud, Solveig Relland, Estelle Bravant, Romain Bouet, Pierre Krolak-Salmon, Nawele Boublay, Denis Fédérico, Alain Pesce, Marc Verny, Frédéric Blanc, Marc Paccalin, Thomas Desmidt, Pierre Grosmaître, Olivier Moreaud, Solveig Relland, Estelle Bravant, Romain Bouet, Pierre Krolak-Salmon

Abstract

Background: One of the crucial challenges for the future of therapeutic approaches to Alzheimer's disease (AD) is to target the main pathological processes responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70, the main population affected by dementia, is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, ageing favours the occurrence of co-lesions of AD, cerebrovascular disease (CVD) and Lewy body dementia (LBD). Most of clinical studies report on functional and clinical disabilities in patients with presumed pure pathologies. But, the weight of co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remains to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages of cognitive disorders. Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan®, amyloid Positron Emission Tomography (PET) and CerebroSpinal Fluid (CSF) AD biomarkers routinely help in performing the diagnosis of underlying lesions. The combination of these measures seems to be of incremental value for the diagnosis of mixed profiles of AD, CVD and LBD. The aim is to determine the clinical, neuropsychological, neuroradiological and biological features the most predictive of cognitive, behavioral and functional impairment at 2 years in patients with co-existing lesions.

Methods: A multicentre and prospective cohort study with clinical, neuro-imaging and biological markers assessment will recruit 214 patients over 70 years old with a cognitive disorder of AD, cerebrovascular and Lewy body type or with coexisting lesions of two or three of these pathologies and fulfilling the diagnostic criteria for dementia at a mild to moderate stage. Patients will be followed every 6 months (clinical, neuropsychological and imaging examination and collection of cognitive, behavioural and functional impairment) for 24 months.

Discussion: This study aims at identifying the best combination of markers (clinical, neuropsychological, MRI, SPECT-DaTscan®, PET and CSF) to predict disability progression in elderly patients presenting coexisting patterns.

Trial registration: NCT02052947 .

Keywords: Alzheimer’s disease; Cerebrovascular disease; Co-lesions; Imaging; Lewy body dementia; Predictive markers.

Conflict of interest statement

Ethics approval and consent to participate

Written informed consent is obtained from subject and caregiver prior to the initiation of the study. The study is carried out in accordance with the French and European Guidelines for Good Clinical Practice, the latest version of the Declaration of Helsinki (Edinburg 2000, Washington 2002, Tokyo 2005) and ICH (International Conference on Harmonisation) Recommendations and Guidelines for Good Clinical Practice.

In accordance with law n° 2004.806 and the ethical body governing biomedical research, the approval of the French ‘Comité de Protection des Personnes’ (CPP) has been submitted to ‘CPP Sud Est III’. CLEM study has been registered in the clinical trials (Current Controlled Trials NCT02052947).

Consent for publication

Not applicable

Competing interests

The authors declare that Avid Radiopharmaceuticals, a Wholly Owned Subsidiary of Eli Lilly & Company has contributed to the funding of 50 doses of Florbetapir for the PET examination.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Aging and the co-occurrence of Alzheimer, vascular and Lewy types

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