TRIAD - Tracking Risk in Integrated Alzheimer's Diagnostics.

Istituti Clinici Scientifici Maugeri SpA

Status: Enrolling

Conditions: Cognitive Decline

Study type: Observational

Funder types: Other

Identifiers

NCT07399418

2025-3.11/337

Details and patient eligibility

About

The study is based on the hypothesis that the integration of biological, psychological, and social factors, according to the biopsychosocial paradigm, allows for more accurate identification of the different stages of the Alzheimer's continuum (AD), facilitating early diagnosis and effective management. It is also hypothesized that the experience of the caregiver is a key element, capable of influencing the patient's experience and clinical course, representing a potential early indicator of risk.

Primary objectives are (PO.1) Jointly analyze biological, psychological, and social factors at different stages of the AD continuum to construct multidimensional clinical profiles and integrated risk models.

(PO.2) Examine the influence of psychological and social variables on the quality of life of patients and caregivers at different stages of the disease.

(PO.3) Investigate the relationship between caregiver psychological well-being and patient cognitive functioning, exploring potentially bidirectional relationships.

Secondary objectives are (SO.1) Compare biomarkers and neuropsychological performance at different stages of the AD clinical continuum.

(SO.2) Evaluate the diagnostic effectiveness of blood and neuroimaging biomarkers in discriminating the severity of cognitive impairment.

(SO.3) Explore stress and coping strategies adopted by caregivers, in relation to the stage of the disease and the quality of the dyadic relationship.

(So.4) Integrate quantitative and qualitative data to understand the emotional experience of the caregiver throughout the entire disease continuum.

Full description

Background

Global aging is leading to an increase in the prevalence of dementia, with an estimated 50 million cases worldwide. Among these, Alzheimer's disease (AD) is the most widespread, characterized by a progressive neurodegenerative course with cognitive, behavioral, and functional symptoms. AD is now considered a pathological continuum with six progressive stages, where the first two, preclinical stages represent a crucial window for early intervention. However, diagnostic methods such as CSF and PET, although effective, are expensive and invasive. Recent research suggests that blood biomarkers of neuroinflammation could offer more accessible solutions.

Understanding the early stages of AD is complicated by their subjectivity, making the use of a purely biomedical model insufficient. The biopsychosocial paradigm integrates biological, psychological, and social aspects, offering a more comprehensive view of the disease. In this context, the role of the caregiver is also central. As AD progresses, the patient becomes dependent, with a direct impact on the quality of life and mental health of the caregiver, who often experiences stress, anxiety, and depression. Work and relationship difficulties increase the emotional and caregiving burden, making it important to consider the caregiver's experience early on in the disease.

Hypotesis and amis

Combining blood-based biomarkers, neuro-imaging, neuro-psychology and psychosocial factors (including caregiver experience), it could be possible to fill four major gaps: (i) scarce presence of scalable, non-invasive tools for very-early detection, (ii) the lack of a frameworks that capture the interaction of biological, psychological and social dimensions during the pre-clinical phases of AD, (iii) a superficial knowledge of how caregivers perceive and deal with AD in its various stages and (iv) the restricted knowledge of mutual influences between the experiences of the caregiver and of the patient.

Primary objectives are (PO.1) Jointly analyze biological, psychological, and social factors at different stages of the AD continuum to construct multidimensional clinical profiles and integrated risk models.

(PO.2) Examine the influence of psychological and social variables on the quality of life of patients and caregivers at different stages of the disease.

(Po.3) Investigate the relationship between caregiver psychological well-being and patient cognitive functioning, exploring potentially bidirectional relationships.

Secondary objectives are (SO.1) Compare biomarkers and neuropsychological performance at different stages of the AD clinical continuum.

(SO.2) Evaluate the diagnostic effectiveness of blood and neuroimaging biomarkers in discriminating the severity of cognitive impairment.

(SO.3) Explore stress and coping strategies adopted by caregivers, in relation to the stage of the disease and the quality of the dyadic relationship.

(SO.4) Integrate quantitative and qualitative data to understand the emotional experience of the caregiver throughout the entire disease continuum.

Ethical considerations

The study will be conducted in accordance with the ethical principles outlined in the Declaration of Helsinki, Good Clinical Practice (Legislative Decree 200/2007), and current regulations on the protection of personal data. In particular, the personal and sensitive data collected will be processed in compliance with Regulation (EU) 2016/679 (GDPR), Legislative Decree 196/2003, and the amendments introduced by Legislative Decree 101/2018. In order to guarantee the confidentiality of the data collected, all data will be pseudonymized by assigning an identification code (initials of the patient's surname and first name, as well as a consecutive number) that allows it to be stored and managed only by authorized personnel.

Sample

Consecutive outpatients, together with their respective caregivers, will be recruited at the Center for Cognitive Disorders and Dementias (CDCD) of ICS Maugeri IRCCS in Montescano, within the Neurophysiopathology Unit and the Diagnostic-Therapeutic Care Pathway for Dementia (DTCP). Patients may be either undergoing their first neurological evaluation for cognitive complaints or already followed by the Center for further diagnostic investigations aimed at the assessment of cognitive decline. Admission to the study will follow specific inclusion and exclusion criteria, which will be verified during the clinical evaluation. After determining the suitability of patients, the neurologist will offer them the opportunity to participate in the research, subject to signing the informed consent form and consent to the processing of personal data. Other imformation are reported in the eligibility section.

Procedure

All patients will undergo an initial clinical and neurological evaluation. Subsequently, routine blood tests will be performed to exclude secondary causes of cognitive impairment, along with structural neuroimaging investigations (magnetic resonance imaging or computed tomography) to rule out additional secondary causes and to assess cortical atrophy and cerebrovascular pathology. When clinically indicated, amyloid positron emission tomography (PET) will also be performed. Patients will then complete a standardized neuropsychological test battery assessing the main cognitive domains.

Based on the integration of these data, the neurologist will assign each patient to one of the following four diagnostic groups along the Alzheimer's disease continuum:

• Subjective Cognitive Decline (SCD): patients reporting subjective cognitive complaints in the presence of neuropsychological performance within normal limits.
• Mixed-etiology Mild Cognitive Impairment (MCI): patients with mild cognitive impairment not specifically attributable to Alzheimer's disease-related pathology.
• Alzheimer's disease-related Mild Cognitive Impairment: patients with mild cognitive impairment and a clinical-instrumental profile consistent with Alzheimer's disease pathology
• Early Alzheimer's disease: patients with mild dementia attributable to Alzheimer's disease.

After assignment to the clinical stage, when clinically appropriated, patients will undergo the assessment of plasma biomarkers of neurodegeneration and neuroinflammation. In addition, patients will complete a series of self-report questionnaires assessing emotional symptoms, perceived stress, quality of life, and cognitive reserve.

Concurrently with the patients' neuropsychological assessment, caregivers will be asked to complete selected self-report questionnaires evaluating caregiver burden, emotional symptoms, coping strategies, metacognitive beliefs, and quality of life. Furthermore, a subgroup of caregivers, selected through convenience sampling to ensure representation across the different patient clinical stages, will participate in a semi-structured interview conducted later.

Enrollment: 80 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (patients):

• Age ≥ 50 years.
• Presence of a primary caregiver, i.e., a person who provides regular care and who can actively participate in the study.
• Understanding of the research objectives and ability to provide informed consent.

Inclusion Criteria (caregivers):

• Be the primary caregiver, providing care for at least six months.
• Age ≥ 18 years, to ensure the ability to understand and actively participate in the study.
• Understanding of the research objectives and ability to provide informed consent.

Exclusion Criteria (patients):

• Age under 50.
• History of previous or concomitant neurological disorders (e.g., severe cerebrovascular accidents, brain tumors, traumatic injuries affecting cognitive functions) and neurodegenerative disorders.
• History of major psychiatric disorders (e.g., schizophrenia, severe bipolar disorder, untreated major depression), alcohol or substance abuse.
• Medical conditions that may interfere with cognitive function (e.g., advanced renal or hepatic failure, severe respiratory disorders, untreated hypothyroidism, B12 deficiency).
• Decompensated systemic diseases with clinical instability and significant organ failure.
• Marked sensory limitations (hearing or vision) and/or language difficulties.
• Participation in other experimental studies involving previous or current involvement in clinical trials of anti-amyloid drugs or experimental drug treatments for AD in the previous 6 months.

Exclusion Criteria (caregivers):

• Presence of severe active psychiatric disorders (e.g., untreated major depression, psychotic disorder, or schizophrenia).
• Difficulty participating in interviews and assessments due to language barriers, cognitive deficits, or other personal limitations.