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

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

Interventions

DEVICE

High-frequency Transcranial Magnetic Stimulation (TMS)

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).

BEHAVIORAL

Digital Cognitive Training

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.

BEHAVIORAL

Structured Physical Exercise

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.

OTHER

Management of Modifiable Vascular and Behavioral Risk Factors

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.

Sponsors & Collaborators

• IRCCS San Raffaele

  lead OTHER

Principal Investigators

• Massimo Filippi, Prof · IRCCS San Raffaele

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-01

Primary Completion

2028-08-01

Completion

2029-08-01

Countries

• Italy

Study Locations