PRedicting the EVolution of SubjectIvE Cognitive Decline to Alzheimer's Disease With Machine Learning

Summary

Alzheimer's disease (AD) has a presymptomatic course which can last from several years to decades. Identification of subjects at an early stage is crucial for therapeutic intervention and possible prevention of cognitive decline. Current research is focused on identifying characteristics of the early stages of AD and several concepts have been developed to that end.

Subjective cognitive decline (SCD) is defined as a self-experienced persistent decline in cognitive capacity in comparison with the subject's previously normal status, during which the subject has normal age-, gender-, and education-adjusted performance on standardized cognitive tests. SCD is not related to current cognitive impairment, however it has been considered for its potential role as risk factors for AD.

The aim of this study is to evaluate, through machine learning tools, the accuracy data, neuropsychological assessment, personality traits, cognitive reserve, genetic factors, cerebrospinal fluid (CSF) neurodegeneration biomarkers, EEG and Event Related Potential recordings in predicting conversion from SCD condition, to Mild Cognitive Impairment (MCI) and AD.

Conditions

• Cognitive Decline
• Mild Cognitive Impairment
• Alzheimer Disease

Interventions

GENETIC

Genetic analysis of APOE and BDNF genes.

The three SNPs (rs429358, rs7412 and rs6265 on APOE and BDNF genes respectively) will be analyzed by the polymerase chain reaction (PCR) on genomic DNA and with the analysis of melting curves (HRMA) using the Rotor-Gene 6,000 (Rotor-Gene, Corbett Research, Mortlake, Australia).

DIAGNOSTIC_TEST

EEG recording

The EEG activity will be recorded continuously from 19 sites by using electrodes set in an elastic cap and positioned according to the 10-20 international system. The recording will be referenced to the common average of all electrodes, excluding Fp1 and Fp2. Re-referencing will be done prior to the EEG artifact detection and analysis. Data will be recorded with a band-pass filter of 0.3-70 Hz and digitized at a sampling rate of 512 Hz and analogue-digital precision was 16 bits (Gal-Nt, EbNeuro®, Florence, Italy). Horizontal and vertical eye movements will be detected by electrooculogram (EOG). Subjects will be sat in a reclined chair for approximately 20 min. Data will be collected at a sampling rate of 256 Hz, with a common mode rejection ratio of 105 dB (decibel), and the following band pass characteristics: 0.1 Hz high-pass filter, 100 Hz fifth order low-pass filter.

DIAGNOSTIC_TEST

CSF collection and AD biomarker measurement

The CSF samples will be collected by lumbar puncture, immediately centrifuged and stored at -80 °C until performing the analysis. Aβ42, Aβ42/Aβ40 ratio, t-tau, and p-tau will be measured using a chemiluminescent enzyme immunoassay (CLEIA) analyzer LUMIPULSE® G600 (Fujirebio, Tokyo, Japan).

DIAGNOSTIC_TEST

Neuropsychological evaluation

For extensive neuropsychological evaluation the investigators will use the following tools: global measurements (MMSE, Information-Memory-Concentration Test), tasks exploring verbal and spatial short- and long-term memory (Digit Span, Corsi Tapping Test, Five Words and Paired Words Acquisition and Recall after 10 min and 24 hr, Short Story Immediate and Delayed Recall), prospective memory (Rivermead Behavioral Memory Test), attention (Trail Making Test A, Dual Task), language (Token Test, naming pictures, Category Fluency Task, Phonemic Fluency Task), constructional praxis (Copying Drawings and Rey-Osterrieth complex figure) and executive function (Trail Making Test B, Stroop Test, Frontal Assessment Battery, Weigl Test). To assess independent living skills, the investigators will use two structured interview: Activities of Daily Living Scale (ADL) and Instrumental Activities of Daily Living Scale (IADL).

DIAGNOSTIC_TEST

Assessment of cognitive reserve, depression, personality traits and leisure activities

In order to estimate premorbid intelligence, all cases will perform TIB test (Test di Intelligenza Breve), an Italian version of the National Adult Reading Test (NART). To assess personality traits of the subjects, the investigators will use the Big Five Factors Questionnaire (BFFQ), that measures the five factors of emotional stability, energy, conscientiousness, agreeableness and openness to culture and experience. For cognitive reserve. subjects will perform structured interviewed regarding participation in intellectual, sporting and social activities, in the course of their life. The presence of depressive symptoms will be evaluated by means of the 22-item Hamilton Depression Rating Scale (HDRS).

DIAGNOSTIC_TEST

Clinical-neuropsychological follow-up

For follow-up assessment, each subject will perform a complete clinical evaluation, an extensive neuropsychological evaluation (27 test), assessment of independent living skills (ADL and IADL), estimation of premorbid intelligence (TIB test) and scale for depression (Hamilton Depression Rating Scale - HDRS).

DIAGNOSTIC_TEST

ERP recording

For ERP acquisition the same EEG system that was used for EEG data acquisition will be used. The participants will be administered an ERP test battery with concurrently recorded EEG consisting of a 3-choice vigilance task (3CVT) designed to evaluate sustained attention and standard image recognition memory task (SIR) designed to evaluate attention, encoding, and image recognition memory. In the SIR, images will be chosen as stimuli to distinguish short term from semantic memory loss and extend previous results of image recognition ERP effects.

Sponsors & Collaborators

• Fondazione Don Carlo Gnocchi Onlus

  collaborator OTHER

• University of Florence

  collaborator OTHER

• Scuola Superiore Sant'Anna di Pisa

  collaborator OTHER

• Azienda Ospedaliero-Universitaria Careggi

  lead OTHER

Principal Investigators

• Valentina Bessi, MD, PhD · Research and Innovation Centre for Dementia-CRIDEM, AOU Careggi, Florence, Italy

Eligibility

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-10-01

Primary Completion

2023-09-30

Completion

2024-03-30

Countries

• Italy

Study Locations