Using Artificial Intelligence to Detect Early Signs of Alzheimer's Disease in People With Memory Concerns

NCT07652931 | Not Yet Recruiting

• 1 other identifier: RF-2024-12380444
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

AHEAD is a prospective, longitudinal, risk-stratified single-arm interventional study enrolling 300 patients with Subjective Cognitive Decline (SCD) at IRCCS San Raffaele Hospital, Milan, Italy. The study uses artificial intelligence (AI) to integrate multimodal data - including MRI, EEG, Optical Coherence Tomography (OCT), neuropsychological assessments, and plasma biomarkers - to identify individuals with underlying Alzheimer's disease (AD) biology and predict cognitive progression. Only participants found to be AD plasma biomarker positive (SCD+) undergo longitudinal follow-up at 12 and 24 months. Participants classified as high risk additionally receive a 6-month personalized multidisciplinary intervention combining high-frequency transcranial magnetic stimulation (TMS), digital cognitive training, structured physical exercise, and targeted management of modifiable vascular and behavioral risk factors.

Conditions

Subjective Cognitive Decline; Alzheimer Disease; Mild Cognitive Impairment; Cognitive Decline

Keywords

Subjective Cognitive Decline; Alzheimer's disease; Artificial Intelligence; Transcranial Magnetic Stimulation; Plasma biomarkers; p-tau217; MRI; EEG; Optical Coherence Tomography; Cognitive Training; Physical Exercise; Brain Health; APOE; Machine Learning; Deep Learning

Outcome Measures

Primary Outcomes (1)

• Diagnostic accuracy of AI models in identifying AD biomarker-positive SCD subjects (AUC)

  Area under the ROC curve (AUC), sensitivity, and specificity of AI models in discriminating between plasma AD biomarker-positive and biomarker-negative SCD subjects, assessed at study entry.

  Baseline (study entry)

Secondary Outcomes (1)

• Predictive accuracy of AI models for cognitive progression (AUC)

  Baseline, 12 months (M12), and 24 months (M24)

Other Outcomes (9)

• Change in Preclinical Alzheimer Cognitive Composite (PACC) score

  Before and after the 6-month intervention (Baseline to Month 6 , or Month12 to Month 18 for rSCD cohort)

• Change in self-perceived quality of life (EQ-5D-3L)

  Before and after the 6-month intervention (Baseline to Month 6 , or Month12 to Month 18 for rSCD cohort)

• Change in 6-minute walking test distance

  Before and after the 6-month intervention (Baseline to Month 6 , or Month12 to Month 18 for rSCD cohort)

Study Arms (1)

SCD Participants

EXPERIMENTAL

All 300 SCD participants undergo baseline multimodal assessment. Those found to be AD plasma biomarker positive (SCD+) undergo longitudinal follow-up at M12 and M24. Those classified as high risk (plasma p-tau217 greater than 0.1325 pg/mL, and/or APOE epsilon4 carrier, and/or elevated CAIDE Dementia Risk Score) additionally receive a 6-month multidisciplinary personalized intervention combining high-frequency TMS, digital cognitive training, structured physical exercise, and targeted vascular and behavioral risk factor management.

Device: High-frequency Transcranial Magnetic Stimulation (TMS); Behavioral: Digital Cognitive Training; Behavioral: Structured Physical Exercise; Other: Management of Modifiable Vascular and Behavioral Risk Factors

Interventions

High-frequency Transcranial Magnetic Stimulation (TMS) DEVICE

High-frequency repetitive TMS (rTMS) delivered according to an intensive protocol during the first 4 weeks of the intervention period (2-3 sessions per week). Applied to brain regions associated with cognitive function to optimize brain health and reduce risk of cognitive decline. Administered by trained professionals following international safety guidelines (Rossi et al., 2009).

SCD Participants

Digital Cognitive Training BEHAVIORAL

Home-based cognitive training delivered via digital platform over 5 months: 2 sessions per week of 30 minutes each. Targets perceived cognitive deficits and related domains (memory, executive functions, attention, visuospatial abilities, language) with progressive adaptation to individual performance level. Compliance monitored via dedicated applications and/or activity diaries. Monthly remote meetings with neuropsychologists to monitor progress.

SCD Participants

Management of Modifiable Vascular and Behavioral Risk Factors OTHER

Personalized pharmacological and non-pharmacological interventions targeting modifiable vascular and behavioral risk factors including blood pressure, cholesterol, BMI, physical inactivity, dietary habits, sleep quality, and social isolation. Monthly remote follow-up visits over 6 months to monitor treatment adherence and optimize risk factor control.

SCD Participants

Structured Physical Exercise BEHAVIORAL

Home-based structured physical exercise program over 5 months: 2 sessions per week of 30 minutes each. Activities include walking, cycling, and global resistance training. An in-person familiarization session is conducted before program start. Monthly remote meetings with physiotherapists to monitor progress and adapt the program. Compliance remotely monitored via dedicated applications and/or activity diaries.

SCD Participants

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Subjective Cognitive Decline (SCD) according to international diagnostic criteria (Jessen et al., 2014).
• Self-experienced persistent decline in cognitive capacity in comparison with a previously normal status and unrelated to an acute event.
• Normal age-, gender-, and education-adjusted performance on standardized cognitive tests used to classify mild cognitive impairment (MCI) or prodromal AD.
• Age greater than or equal to 40 years.
• Native Italian Speaker.
• Stable pharmacological treatment for at least 4 weeks prior to enrollment.
• Provision of oral and written informed consent to study participation.

You may not qualify if:

• Presence of MCI, prodromal AD, or dementia.
• Any major systemic, psychiatric, or neurological disturbance.
• Medical conditions or substance abuse that could interfere with cognition.
• Pacemaker and/or other implanted neurostimulation devices in the head/neck district.
• Contraindications to undergoing MRI examination.
• Brain damage at routine MRI, including extensive cerebrovascular disorders.
• Traumatic or surgical wounds that could determine a risk of infection at the site of non-invasive stimulation.
• Scalp alterations that could determine the spread of excessive current from the device.
• Known history of epilepsy (due to small risk of seizure induction from rTMS in epileptic patients).
• Denial of oral and written informed consent to study participation.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

San Raffaele Neurology Unit

Milan, Milano, 20132, Italy

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Motor Activity

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Behavior

Study Officials

• Massimo Filippi, Prof

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federica FA Agosta, MD

CONTACT

0226433051; agosta.federica@hsr.it

Elisa EC Canu, PhD

CONTACT

0226433033; canu.elisa@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD

Model Details: Prospective, longitudinal, risk-stratified single-arm interventional study. Not all participants receive the intervention: only those classified as high risk based on plasma biomarkers (p-tau217), APOE genotype, and/or cardiovascular risk profile (CAIDE score) receive the 6-month multidisciplinary intervention program.

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 17, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: June 17, 2026

Record last verified: 2026-06

Locations

IT (1)