Sustainable Method for Alzheimer's Prediction

Alzheimer Disease Clinical Trial

Official title:

Sustainable Method for Alzheimer's Prediction in Mild Cognitive Impairment: EEG Connectivity and Graph Theory Combined With ApoE Testing.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03654911
• Other study ID #: ROSSINI_MSD_ID1764
• Status: Completed
• Start date: April 11, 2018
• Est. completion date: January 31, 2020

Study information

• Verified date: July 2020
• Source: Catholic University of the Sacred Heart
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an observational study with the aim of validating, in a consistent population sample, with appropriate follow-up, whether EEG connectivity analysis combined with the neuropsychological evaluation and ApoE genotype testing in aMCI could be of help in early identification of converted aMCI as a first-line screening method in order to intercept early those subjects with a high risk for rapid progression to AD.

Description:

Primary aim of the present project is to investigate the dynamic connectivity among brain centers by using a mathematical (Small World) approach to the analysis of EEG-related neural networks. The aim is to provide reliable discrimination of amnesic-Mild Cognitive Impairment (a MCI) subjects who, on individual basis, will rapidly convert to Alzheimer Disease (AD) after a relatively brief follow-up. Moreover, keeping in mind that the epsilon-4 allele of the ApoE gene is a genetically determined risk factor for pathogenesis of late-onset AD, a secondary endpoint is introduced to investigate whether the EEG connectivity markers together with a genetically determined risk of dementia as represented by ApoE testing can reach higher sensitivity/specificity for early discrimination of MCI converting to AD

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: January 31, 2020
• Est. primary completion date: June 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Exclusion criteria for AD will be:

• frontotemporal dementia;

• behavioural variant of frontotemporal dementia;

• vascular dementia;

• extra-pyramidal syndromes;

• reversible dementias (including pseudodementia of depression);

• Lewy body dementia.

The exclusion criteria for aMCI will be:

• mild AD, as diagnosed by standard protocols including National Institute on Aging-Alzheimer's Association workgroups (McKhann et al. 2011);

• evidence (including magnetic resonance imaging -MRI procedures) of concomitant dementia such as frontotemporal, vascular and reversible dementias (including pseudo-depressive dementia), marked fluctuations in cognitive performance compatible with Lewy body dementia and/or features of mixed dementias;

• evidence of concomitant extrapyramidal symptoms;

• clinical and indirect evidence of depression as revealed by the Geriatric Depression Scale GDS (Yesavage et al. 1982); scores lower than 14 (no depression);

• other psychiatric diseases, epilepsy, drug addiction, alcohol dependence, use of neuro/psychoactive drugs including acetylcholinesterase inhibitors;

• current or previous uncontrolled or complicated systemic diseases (including diabetes mellitus) or traumatic brain injuries.

Related Conditions & MeSH terms

• Alzheimer Disease
• Amnestic-Mild Cognitive Impairment
• Cognitive Dysfunction

Intervention

Diagnostic Test:
• EEG
EEG

Genetic:
• ApoE
ApoE

Locations

Country	Name	City	State
Italy	Fondazione Policlinico A.Gemelli IRCCS, Università Cattolica del Sacro Cuore	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Catholic University of the Sacred Heart

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Vecchio F, Miraglia F, Iberite F, Lacidogna G, Guglielmi V, Marra C, Pasqualetti P, Tiziano FD, Rossini PM. Sustainable method for Alzheimer dementia prediction in mild cognitive impairment: Electroencephalographic connectivity and graph theory combined with apolipoprotein E. Ann Neurol. 2018 Aug;84(2):302-314. doi: 10.1002/ana.25289. Epub 2018 Aug 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarkers: EEG	EEG recording will be performed at rest, with closed eyes from routine electrode scalp positions according to the International 10-20 system. Functional connectivity analysis will be performed using eLORETA evaluating intracortical Lagged Linear Coherence. Weighted and undirected networks will be built from the above measure. Small World parameter is a dimentionless number that will be assessed as Biomarker of brain connectivity networks, since it measures the balance between local connectedness and the global integration of a network, representing brain network organization. Small world index will be computed in the seven EEG frequency bands delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz) and gamma (30-45 Hz) (Vecchio et al., 2018 doi: 10.1002/ana.25289)	2 years
Primary	Biomarker: ApoE4	It will be evaluated the allele of the Apo-E gene as biomarker for the pathogenesis of late-onset and sporadic AD. The Apo-E test provides a dimentionless value represented by the type of the allele (e2, e3,e4).	2 years
Secondary	Biomarker: Accuracy of digital classifier	Secondary endpoint will be to investigate whether EEG connectivity markers (small world ) along with genetically determined risk-indicators for dementia, as represented by Apo-E testing can reach a greater sensitivity, specificity and accuracy for a digital classifier (i.e. an algorithm that solve the problem of identifying to which of a set of categories a new observation belongs) able to predict the MCI conversion to AD. The accuracy value is dimentionless number represented by a percentual value and it is the biomarker for the ability of the classifier for the early identification of AD (Vecchio F. et al., 2018 doi: 10.1002/ana.25289)	2 years