Effectiveness of Genistein in Mild Cognitive Impairment

The primary variable to be evaluated is the change in overall cognitive function and the deterioration in the ability to perform activities of daily living, assessed through the mean change by the Integrated Alzheimer's Disease Rating Scale (iADRS) score.

iADRS is an assessment tool designed to comprehensively measure cognitive and functional decline in patients with Alzheimer's disease, especially in the early stages. It combines elements of cognitive and functional assessment in a single scale, using ADAS-Cog and ADCS-ADL. In this case, version ADAS-Cog14 was used.

The Mini-Mental State Examination (MMSE) is one of the most widely used tools for detecting and assessing cognitive impairment, including Alzheimer's disease. It is a brief and simple test that evaluates various cognitive functions: spatial and temporal orientation, immediate memory, attention and calculation, delayed memory, language, praxis (naming, repetition, comprehension of verbal commands, reading, spontaneous writing and copying drawings) and visual construction.

The GDS-15 (Geriatric Depression Scale - 15 items). This instrument was specifically designed for use in elderly populations to detect possible depression. It consists of 15 items with dichotomous yes/no responses.

CDR-SB: A semi-structured interview with the primary informant and the patient, evaluated according to the evaluator's clinical judgment. It assesses the domains of Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care, with greater emphasis on the first domain.

ADAS-Cog: This test aims to measure the severity of dementia (global cognition, memory, language, etc.). The ADAS-Cog14 was chosen, which adds additional items (delayed word recall, digit cancellation, and maze or verbal fluency test) to the original test, improving the scale's sensitivity without significantly increasing assessment time.

The ADCS-ADL and ADCS-ADL-MCI questionnaires assess functionality but they are aimed at different populations. ADCS-ADL aims to assess functionality in activities of daily living. ADCS-ADL-MCI, on the other hand, aims to assess the impact of Mild Cognitive Impairment (MCI) on Activities of Daily Living (ADLs).

DAD-E: It aims to evaluate the functional impact of dementia on activities of daily living, through a questionnaire applied to the main informant.

The TAVEC (Test de Aprendizaje Verbal España-Complutense) is a neuropsychological tool widely used in Spain and other Spanish-speaking countries. It aims to assess episodic verbal memory, including learning, immediate recall, delayed recall, recognition, attention, and sensitivity to interference.

The Trail Making Test (TMT) is a widely used neuropsychological test. It aims to assess processing speed, sustained and divided visual attention, visual tracking, executive functions (cognitive flexibility), and cognitive flexibility.

The Clock Drawing Test (CDT) aims to evaluate visuospatial abilities and skills, visual memory and executive functions (strategy, organization).

The Rey-Osterrieth Test is a widely used neuropsychological test for assessing visual memory, visuospatial perception, and executive functions. These functions are often affected in Alzheimer's disease, making this test useful in its assessment.

Digit Span: It aims to assess short-term verbal memory (forward span) and auditory-verbal working memory (reverse span), as well as attention, sequencing, and mental manipulation of information.

Semantic fluency is a neuropsychological test. It aims to evaluate lexical-semantic access capacity, knowledge organization in memory, executive functions (planning, initiation, flexibility, response control), and semantic memory. This test is particularly useful for assessing executive function and language, two areas that are often affected in Alzheimer's disease.

The F.A.B. (Frontal Assessment Battery) is a brief neuropsychological tool designed to assess executive functions, which are often affected in Alzheimer's disease and other dementias. It aims to evaluate executive functions (conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, autonomy) by combining verbal instructions with tasks that require verbal responses or motor actions.

Positron emission tomography is a molecular imaging technique that measures the activity of a radiopharmaceutical that marks ß-amyloid (βA) plaques through the SUV (standard uptake value), which should be based on the amount of AB and can be relativized to match the change we expect to see. The mean change from baseline to month 18 in the standard uptake value (SUV) of composite cortical amyloid will be evaluated using the amyloid tracer [18F] flutemetamol by positron emission tomography (PET) imaging.

The inclusion of serum biomarkers may offer a more comprehensive perspective on the underlying mechanisms and response to treatment.

Take into account associated diseases, such as hypertension, diabetes, dyslipidemia, and other chronic diseases suffered by the patient, as well as concomitant medication. Document all medications that participants are taking at the start of the study or during its course, especially those that may influence cognitive function.

Age and gender; educational level; age and year of birth; tobacco and/or alcohol consumption.

The safety of investigational products (IPs) will be assessed by recording adverse events (AEs) throughout the study, i.e., from the baseline visit to the final visit and a blood test.