TRIAD - Tracking Risk in Integrated Alzheimer's Diagnostics. A Biopsychosocial Model for the Early and Accurate Diagnosis of the Alzheimer's Disease Continuum.

Mini Mental State Examination (MMSE)

时间窗: Baseline

This test is used for rapid screening of overall cognitive functioning. It consists of eleven items in different cognitive areas to obtain an overall score of cognitive functioning. Total scores range from 0 to 30 points. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Age of participants

时间窗: Baseline

Mean age of patients and caregivers assessed at study entry.

Montreal Cognitive Assessment (MoCA)

时间窗: Baseline

It is a cognitive screening test used in the assessment of dementia. The MoCA consists of several items that assess the following cognitive functions: visuospatial and executive functions, naming, attention, language, abstraction, memory, and spatial-temporal orientation. The score ranges from 0 to 30. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Mental Deterioration Battery (MDB)

时间窗: Baseline

It is a battery of neuropsychological tests developed to assess cognitive decline, often used to diagnose and monitor cognitive disorders such as AD. The battery includes verbal memory tests (Rey's 15 words, immediate and delayed recall), phonemic verbal fluency, sentence construction, Raven's Progressive Matrices, immediate visual memory, freehand drawing copying, and programmed drawing copying. Each test is corrected independently. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Free and Cue Selective Reminding Test (FCSRT)

时间窗: Baseline

is used to assess episodic memory and recall ability. The test consists of four main phases: learning phase, free recall, guided recall, and delayed recall. The final score is calculated by adding the scores from the different phases. Poor free recall but good guided recall suggests a retrieval deficit, which is compatible with normal aging. On the other hand, a low score in both conditions indicates memory consolidation difficulties. N.B. This information will be collected only for the patients.

Frontal Assessment Battery (FAB)

时间窗: Baseline

It is a test consisting of 6 items that measure conceptualization of similarity, lexical fluency in phonemic mode, motor planning, conflicting instructional responses, the go-no go task, and grasping behavior. Each item is scored on a scale from 0 to 3, with a maximum raw score of 18 points. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Sex distribution of participants

时间窗: Baseline

Number and percentage of patients and caregivers by sex.

Digit Span forward-backward

时间窗: Baseline

It is used to assess short-term verbal memory and verbal working memory. The test consists of two different tasks. The first task (forward) assesses short-term verbal memory and requires the assessor to read a sequence of numbers that the patient must then repeat in the same order. The second test (backward) assesses verbal working memory and requires the patient to repeat the sequence of numbers in reverse order to that read by the evaluator. The sequences gradually increase in difficulty, starting from a minimum of three digits up to a maximum of nine for the forward test and eight for the backward test. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Span di cubi forward-backward

时间窗: Baseline

Psychometric tool used to assess short-term visuospatial memory and visuospatial working memory. The first test (forward) assesses short-term visuospatial memory and requires the evaluator to touch a sequence of cubes arranged on a board and the patient to repeat the sequence by touching the cubes in the same order. The second test (backward) assesses visuospatial working memory and requires the examiner to tap a sequence of cubes, which the patient must then repeat in reverse order. The sequences of cubes to be tapped gradually increase in difficulty, starting from a minimum of three cubes up to a maximum of nine for the forward test and eight for the backward test. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Phonemic fluency

时间窗: baseline

It assesses vocabulary access and verbal fluency based on phonemic cues. It consists of three tests in which the patient must generate as many words as possible beginning with a specific letter (F, A, and S) in 60 seconds for each letter. The total raw score is the sum of the number of correct words generated for each letter within the time limit. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Semantic fluency

时间窗: Baseline

Twop different test are included. Both assesse vocabulary access and verbal fluency on semantic prompts. Both consist of rials in which the patient must generate as many words as possible belonging to each of the following categories. For the first test categories are colors, animals, and fruits. instead, for the secon test categories are birds and pices of fornuture. The time allowed for each category is 60 seconds. The total raw score is the sum of the number of correct words generated for each letter within the time limit. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Trail Making Test (TMT) A-B

时间窗: Baseline

A tool used to assess divided attention, visuomotor coordination, and the ability to alternate conceptual settings. Specifically, this test consists of two trials. Trial A (TMT-A) requires the patient to connect a list of randomly arranged numbers in ascending order as quickly as possible. Test B (TMT-B), on the other hand, requires the subject to connect alternating numbers and letters in the shortest possible time. The letters must be connected in alphabetical order and the numbers in ascending order. Shorter completion times indicate better performances. N.B. This information will be collected only for the patients.

Stroop test

时间窗: Baseline

It assesses selective attention and executive functions, with particular focus on inhibitory interference and cognitive flexibility. The test is divided into three parts of increasing difficulty. The first test consists of reading a list of colors. The second test requires the patient to name the color of the ink with which the circles are printed. Finally, in the third test, the patient is asked to name the color of the ink with which the names of the different colors are written. The patient is asked to try as quickly as possible and to continue the exercise even if they make mistakes. At the end, two raw scores are obtained: one for the completion time (with shorter completion times show better performances) and one for the number of mistakes made (with lower errors indicating a better performance) N.B. This information will be collected only for the patients.

Rey-Osterrieth Complex figure (ROCF)

时间窗: Baseline

This test consists of two different tasks. The first, ROCF copy, assesses visuospatial and motor planning skills. It consists of copying a complex figure as accurately as possible. The second test, or ROCF with 15-minute recall, assesses long-term visuospatial memory. Fifteen minutes after being shown a complex figure-a period during which the subject performs other non-interfering tasks-the subject is asked to reproduce the figure without being able to review it. For both of the trials, the total score is from o to 36. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Multiple Features Target Target Cancellation

时间窗: Baseline

This test evaluates executive functioning. The patient is given a sheet containing a grid of visual stimuli, including both targets and distractors. They are then asked to cross out all the targets that correspond to the target stimulus. The execution time, the number of correctly identified targets, and the number of errors (number of distractors crossed out) are then recorded. These last two data points are then combined to calculate the accuracy index. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Educational level of participants

时间窗: Baseline

Years of formal education completed by patients and caregivers.

Clock Drawing Test (CDT)

时间窗: Baseline

It is a brief neuropsychological screening tool used to assess global cognitive functioning, with particular sensitivity to executive functions, visuospatial abilities, attention, and planning. It includes three trials: a free-drawing condition, a pre-drawn circle condition, and a copy condition. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Naming of colored photographs

时间窗: Baseline

It is a neuropsychological test used to assess lexical and semantic abilities, specifically object naming based on visual stimuli. The test consists of presenting a series of images depicting common objects, which the participant is required to name verbally. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Episodic Memory Score

时间窗: Baseline

It is a composite index derived from standardized episodic memory tasks. It is designed to provide a synthetic and robust estimate of episodic memory functioning, reducing task-specific variability and enhancing sensitivity to early memory impairment. Lower scores indicate worse performances. N.B. This information will be collected only for the patients.

Semantic-Phonological Delta

时间窗: Baseline

It is a difference score calculated from verbal fluency tasks by subtracting phonological fluency performance from semantic fluency performance. This index captures the relative imbalance between semantic memory and executive-phonological processes. A reduced or negative delta reflects a disproportionate impairment in semantic fluency relative to phonological fluency. N.B. This information will be collected only for the patients.

Body Mass Index (BMI)

时间窗: Baseline

BMI calculated as weight in kilograms divided by height in meters squared (kg/m²).

Patient Health Questionnaire 9 (PHQ-9)

时间窗: Baseline

It is a psychological screening tool used to assess the severity of symptoms typical of major depressive disorder. The patient responds to the items by thinking about the frequency with which they have experienced the difficulties described in the last two weeks. Each item is rated on a 4-point Likert scale ranging from 0 (never) to 3 (almost every day). The total score, out of a maximum of 27 points, is given by the sum of the scores obtained for each item. Five levels of clinical severity have been identified, based on specific cut-offs: no depression (0-4 points), mild depression (5-9 points), moderate depression (10-14 points), moderately severe depression (15-19 points), and severe depression (20 or more points). N.B. This information will be collected both for patients and caregivers.

Generalized Anxiety Disorder (GAD-7)

时间窗: Baseline

It is a psychological screening tool used to assess the severity of symptoms typical of generalized anxiety disorder. It is a self-report questionnaire consisting of 7 items. The patient responds to the items by thinking about the frequency with which they have experienced the difficulties described in the last two weeks. Each item is rated on a 4-point Likert scale ranging from 0 (never) to 3 (almost every day). The total score, out of a maximum of 21 points, is given by the sum of the scores obtained for each item. Four levels of clinical severity have been identified, based on specific cut-offs: no anxiety (0-4 points), mild anxiety (5-9 points), moderate anxiety (10-14 points), and severe anxiety (15 or more points). N.B. This information will be collected both for patients and caregivers.

Perceived Stress Scale 10 (PSS-10)

时间窗: Baseline

It is a scale used to measure an individual's perceived stress level over the past four weeks. The aim is not to measure 20 specific areas, but rather the extent to which a person perceives their life as unpredictable or difficult to manage. The short version, in its Italian translation, has 10 items, each of which is rated on a 5-point Likert scale ranging from 0 (never) to 4 (very often). The total score (40 points) is given by the sum of the scores obtained for each item. N.B. This information will be collected both for patients and caregivers.

Metacognitions Questionnaire-30 (MCQ-30)

时间窗: Baseline

It is a self-report questionnaire consisting of 30 items, developed to assess metacognitive processes related to thought regulation and dysfunctional beliefs about mental functioning. It investigates five main metacognitive dimensions: (1) positive beliefs about worries; (2) negative beliefs about the uncontrollability and dangerousness of thoughts; (3) cognitive confidence; (4) need to control thoughts; (5) cognitive self-awareness. Each item is rated on a 4-point Likert scale from 1 (strongly disagree) to 4 (strongly agree), providing a total score and five subscores. N.B. This information will be collected both for patients (only those specifically selected according to their clinical diagnosis) and caregivers.

Cognitive Function Instrument self-report (CFI self-report)

时间窗: Baseline

This tool was created to assess patients' subjective perception of cognitive changes. It is useful for detecting and monitoring the early symptoms typical of neurocognitive disorders. The questionnaire consists of 14 items, each with three possible answers: yes (1 point), maybe (0.5 points), no (0 points). The final score (14 points) is given by the sum of the scores obtained for each item. The average reference score is 2.44±3.30. The higher the score obtained, the greater the cognitive difficulties self-perceived by the patient. N.B. This information will be collected only for the patients.

Cognitive Reserve Index Questionnaire short form (s-CRIq)

时间窗: Baseline

This is a tool designed to assess cognitive reserve. The questionnaire investigates three macro-aspects: education, occupation, and leisure activities. Four scores are obtained from the questionnaire: cognitive reserve index related to education level (CRI education), cognitive reserve index related to work experience (CRI work), cognitive reserve index based on leisure activities (CRI leisure), and overall cognitive reserve index calculated as the average of the three sub-indices (CRI). The scores are grouped into five different levels of cognitive reserve: low (points \< 70), medium-low (71 \< points \< 84), medium (85 \< points \< 114), medium-high (115 \< points \< 130), and high (points \> 130). N.B. This information will be collected both for patients and caregivers.

EuroQoL 5D e EuroQoL VAS

时间窗: Baseline

The EuroQoL 5d is a questionnaire that explores five different sections (mobility; personal care; usual activities; pain, discomfort, or distress; anxiety and depression) through various items that can be answered using a three-level Likert scale ranging from 1 (no problem) to 3 (severe problem). At the end of the administration, a 5-digit number is produced that represents the current and perceived quality of life. The EuroQoL VAS, on the other hand, is a visual analog scale that represents a graduated thermometer, whose temperature corresponds to the perceived quality of life. The scale ranges from 0 (worst possible health condition) to 100 (best possible health condition), and the respondent is asked to estimate their current level of health by marking the temperature that best represents it. N.B. This information will be collected both for patients and caregivers.

Multidimensional Assessment of Subjective Cognitive Decline (MASCoD)

时间窗: Baseline

It is a multidimensional screening tool designed to detect the memory and executive deficits that characterize SCD, helping to facilitate the differential diagnosis process and the identification of risk factors. The form includes a general section (aimed at collecting general clinical and sociodemographic information) and three specific sections. Section A (10 items) examines the main risk factors, comorbidities, and the possible presence of biomarkers. Section B (11 items) assesses subjectively perceived disturbances in memory and tasks involving attentional and executive functions. Finally, section C investigates the possible presence of psychological symptoms using items from the GAD-2 and PHQ-2. The total test score is given by the sum of the scores obtained in sections A and B (0-21). Three risk categories are identified: low risk (0-7 points), medium risk (8-13 points), and high risk (14-21 points). N.B. This information will be collected only for the patients.

Clinical and lifestyle characteristics

时间窗: Baseline

Number and percentage of participants presenting comorbidities, regular physical activity, tobacco use, alcohol consumption, and current medical therapy.

Cognitive Function Instrument partner-report (CFI partner-report)

时间窗: Baseline

It is a tool created to assess a partner or caregiver's perception of a patient's cognitive difficulties. It is useful for identifying and monitoring early cognitive changes. The questionnaire consists of 14 items, each with three possible answers: yes (1 point), maybe (0.5 points), no (0 points). The final score (14 points) is given by the sum of the scores obtained for each item. The average reference score is 2.30±2.22. The higher the score obtained, the greater the cognitive difficulties found in the patient. N.B. This information will be collected only for the caregivers.

Caregiver Burden Inventory (CBI)

时间窗: Baseline

It is a questionnaire developed to measure the perceived burden of caregivers. It consists of 24 items organized into five subscales (objective time burden, developmental burden, physical burden, social burden, emotional burden). Each item is rated on a 5-point Likert scale with scores ranging from 0 (not at all) to 4 (extremely). The score (0-96) is higher the greater the perceived level of burden. Four levels of clinical severity have been identified, based on specific cut-offs: low burden (0-24), moderate burden (25-48), high burden (49-72), and very high burden (73-96). They are also analyzed separately to identify areas of greatest difficulty. N.B. This information will be collected only for the caregivers.

COPE NVI

时间窗: Baseline

It is a psychological questionnaire developed to assess the coping strategies used by a person to deal with stress. Specifically, it is a short Italian adaptation of the original version. It consists of 60 items that investigate coping strategies attributable to five main factors (avoidance, social support, positivity, problem solving, emotional distrust). Each item is rated on a 4-point Likert scale with scores ranging from 1 (I never do this) to 4 (I do this a lot). The score is calculated by adding up the responses for each subscale, providing a profile of the coping strategies adopted by the subject. N.B. This information will be collected only for the caregivers.

Instrumental Activity of Daily Living (IADL)

时间窗: Baseline

It is a scale used to assess the patient's level of independence in basic and instrumental activities of daily living. Eight complex functions are investigated (using the telephone, shopping, using transportation, cooking (only for women), doing housework (only for women), doing laundry (only for women), handling money, taking medication) and evaluated by assigning a score of 0 or 1. The total score is calculated by adding up the points assigned for each item. The maximum score varies between the two sexes. Specifically, it ranges from 0-8 for women and 0-5 for men. The higher the score, the greater the independence in basic daily instrumental activities. N.B. This information will be collected only for the caregivers.

Basic Activity of Daily Living (BADL)

时间窗: Baseline

It is a scale for assessing basic activities related to the patient's daily life. The scale investigates six activities (bathing; dressing; toileting; continence; moving around; eating) to which a score from 0 to 1 can be assigned (three alternatives in total, where two options share the same score, i.e., plausible alternatives that share the same level of severity). A score of 0 is assigned if the subject is dependent and a score of 1 if independent. The total score is calculated by adding up the points assigned for each item. The maximum score obtainable is 6, indicating total autonomy in activities of daily living. N.B. This information will be collected only for the caregivers.

Neuropsychiatric Inventory (NPI)

时间窗: Baseline

Developed to assess neuropsychological symptoms in patients with dementia or other neurological conditions. It investigates 12 neuropsychiatric domains (delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, euphoria/excitement, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, sleep disturbances, eating disturbances), for each of which the presence or absence of the symptom must be noted. If the presence of the symptom is reported, its frequency (from 1=rarely to 4=very frequently) and severity (from 1=mild to 3=severe) must be assessed. Finally, the total score for the domain is calculated by multiplying the frequency by the severity. The total NPI score is obtained by adding the scores for all 12 domains (range 0-144). In general, scores between 0-10 indicate mild symptoms, between 11-30 moderate symptoms, and greater than 30 severe symptoms. N.B. This information will be collected only for the caregivers.

Family Strain Questionnaire-Short Form (FSQ-SF)

时间窗: Baseline

It is a screening tool designed to gather information on the situation experienced by a primary caregiver in the context of care. It consists of 30 items and a binary response scale (yes/no) and is particularly relevant for detecting psychological issues that warrant urgent, seriously recommended, recommended, or non-recommended psychiatric referrals/reports. N.B. This information will be collected only for the caregivers.

Semi-structured interview for caregivers

时间窗: Baseline

It will allow qualitative information to be gathered on the caregiver's experience in the daily management of patients with symptoms attributable to the AD continuum. It will aim to explore the burden of care, the perception of the disease, the emotional relationship between caregiver and patient, and the coping strategies adopted. In addition, future expectations and unmet needs will be explored. The interview questions will be organized according to a funnel approach, starting with more general aspects and then delving into more sensitive topics. Only a selected sub-sample of caregivers will participate in the interview. N.B. This information will be collected only for the caregivers.

MRI or TC

时间窗: Baseline

In accordance with clinical guidelines, one of the following neuroimaging examinations will be performed to exclude secondary causes of cognitive impairment and to assess the presence of cortical atrophy and cerebrovascular disease. N.B. This information will be collected only for the patients.

Plasma Concentration of Routine Blood Chemistry Parameters

时间窗: Baseline

In accordance with clinical guidelines, blood tests will be performed to exclude secondary causes of cognitive impairment. N.B. This information will be collected only for the patients.

Plasma Concentration of Neurodegeneration and Neuroinflammation Biomarkers

时间窗: Baseline

In a sample selected according to specific clinical criteria, plasma concentrations of blood biomarkers of neurodegeneration (Aβ40, Aβ42, p Tau181, and NfL) and blood biomarkers of neuroinflammation (GFAP, sTREM2, YKL40) will be analyzed. N.B. This information will be collected only for the patients.

Amyloid PET or FDG-PET

时间窗: Baseline

In a selected subgroup of patients, FDG-PET or amyloid PET will be performed based on diagnostic appropriateness and predefined clinical criteria. FDG-PET will be used to assess regional cerebral glucose metabolism as an index of neuronal dysfunction, while amyloid PET will be used to evaluate cerebral amyloid burden, supporting etiological characterization of cognitive impairment. N.B. This information will be collected only for the patients.