The goal of this multicenter prospective observational cohort study is to better understand the clinical, neuropsychological, and biological characteristics of individuals attending Brain Health Services (BHS) in the Lombardy region. The study focuses on adults with subjective cognitive decline (SCD), functional cognitive disorder (FCD), or "well worried" individuals without objective cognitive impairment.
The main questions it aims to answer are:
* What clinical, cognitive, and biological differences exist between individuals who are positive versus negative for Alzheimer's disease (AD) plasma biomarkers (p-tau217) at baseline? * What factors predict positivity to AD biomarkers at baseline? * How does communication of biomarker results (risk disclosure) affect psychological well-being shortly after receiving results? * What factors predict longitudinal changes in AD biomarkers over 5 years? * Do baseline biomarkers predict the development of mild cognitive impairment (MCI) or dementia during follow-up?
Participants will:
* Undergo standard clinical evaluation at their local BHS * Provide blood samples for plasma biomarker analysis (e.g., p-tau217, GFAP, NfL, ApoE) * Undergo neuropsychological testing and cognitive screening * Complete questionnaires assessing psychological impact and risk perception (before and after biomarker disclosure) * Undergo additional center-specific procedures when clinically indicated (e.g., MRI, lumbar puncture, polysomnography) * Be followed annually for 5 years
The study plans to enroll approximately 1000 participants across multiple BHS in Lombardy and will follow them for a total duration of 7 years. The results will help clarify the role of biomarkers in early cognitive complaints and support the development of preventive strategies within BHS.
Adults (≥18 years)
Diagnosis of SCD, FCD, or "well worried" individuals without objective cognitive impairment
Evaluation at one of the Lombardy BHS
Ability to provide written informed consent
Diagnosis of mild cognitive impairment or dementia at baseline visit
Enrollment in another interventional study with an expected effect on cognition
Pregnancy or breastfeeding
Subjects accessing BHS in Lombardy with SCD, FCD or "well worried" individuals without objective cognitive impairment
Cohort
Prospective
Not listed
Clinical, neuropsychological, and biological patterns associated with AD plasma biomarker positivity at baseline
Identification of multivariate patterns (e.g., principal component analysis and clustering methods) differentiating individuals positive versus negative for Alzheimer's disease plasma biomarker (p-tau217) at baseline, based on demographic, clinical, neuropsychological, radiological, and biological variables.
Psychological impact of biomarker disclosure at1 week
Change in psychological measures (Hospital Anxiety and Depression Scale - HADS; Impact of Event Scale - Revised - IES-R) before and one week after communication of biomarker results.
Predictors of AD plasma biomarker positivity at baseline
Identification of demographic, clinical, neuropsychological, and radiological predictors of baseline AD plasma biomarker positivity, assessed using logistic and regression models.
Predictors of longitudinal changes in AD biomarkers
Identification of clinical, neuropsychological, and radiological predictors of longitudinal changes in plasma AD biomarkers over time using linear mixed-effects models.
Predictors of conversion to MCI or dementia
Evaluation of clinical, biological (plasma and CSF biomarkers), radiological, and neuropsychological predictors of progression to mild cognitive impairment (MCI) or dementia using survival analysis (Kaplan-Meier and Cox models).
Predictive performance of plasma biomarkers for AD diagnosis
Assessment of diagnostic accuracy of plasma biomarkers (neurodegeneration, Alzheimer's pathology, neuroinflammation markers) in predicting CSF biomarker positivity for AD using logistic regression models and ROC curve analysis.
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