Efficacy of MEMORMAX in Subjects With MCI

Effect of Memormax on global cognitive performance in patients with mild Mild Cognitive Impairment (MCI) after a 6 months treatment and compared to placebo (T0-T6), measured by the FREE AND CUED SELECTIVE REMINDING TEST (FCRST)

Effect of Memormax on global cognitive performance in patients with mild Mild Cognitive Impairment (MCI) after a 6 months treatment and compared to placebo (T0-T6), measured by the ADDENBROOKE'S COGNITIVE EXAMINATION (ACE-R) tests.

To evaluate the effect of Memormax on global cognitive performance across the entire population studied in a 6-month open-label extension phase (T6-T12), measured by the FCSRT

To evaluate the effect of Memormax on global cognitive performance across the entire population studied in a 6-month open-label extension phase (T6-T12), measured by the ACE-R

Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. The MMSE test includes simple questions that are valuated using point subscales that are summed to have a maximunm of 30 points; the administration of the test takes between 5 and 10 minutes and cognitive functions of each patient are examinated as reported below; Orientation to time (0-5 points), Orientation to place (0-5 points), Registration (0-3 points), Attention and calculation (0-5 points), Recall (0-3 points), Language and Praxis (0-9 points).

If the score is greater than or equal to 24, patient has a normal cognition. Below 24 points, we can indicate a severe cognitive impairment (≤9 points), a moderate cognitive impairment (10-18 points) and a mild cognitive impairment (19-23 points). For these reasons, higher values represent a better outcome

A digit-span task is used to measure working memory's number storage capacity. Participants see or hear a sequence of numerical digits and are tasked to recall the sequence correctly, with increasingly longer sequences being tested in each trial. The participant's span is the longest number of sequential digits that can accurately be remembered.measured with further tests that explore multiple cognitive functions compared to evaluations as primary objectives.

The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy.The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning.

Babcock Story Recall Test (BSRT; Babcock &. Levy, 1940) is a verbal memory measure in which participants are read a brief story and asked to provide a summary of the story.

The Rey 15-Item test is a test designed by Rey (1964) to detect malingering.

Raven's Progressive Matrices (often referred to simply as Raven's Matrices) or RPM is a nonverbal group test typically used in educational settings. It is usually a 60-item test used in measuring abstract reasoning and regarded as a non-verbal estimate of fluid intelligence

The original TT tested auditory verbal memory by having the subject point to tokens of 5 different colors, 2 shapes (circle, squares), and 2 sizes (small, large), in response to commands such as "touch the blue circle" (a one dimensional command, or 1-D, since the tokens differ only by color), or "touch the yellow square and the red circle" (a two dimensional command, or 2-D, since the tokens differ by color and/or shape), or "touch the small red circle and the large green square" (a three dimensional command, or 3-D, since the tokens differ by size, and/or color and/or shape).

Verbal fluency tests are a kind of psychological test in which participants have to produce as many words as possible from a category in a given time (usually 60 seconds)

NEPSY-II is the only single measure that allows the clinician to create a tailored assessment across the following domains: Executive functioning, Attention Language, Memory and learning, Sensorimotor functioning, Social perception, Visuospatial processing. The results provide information relating to typical childhood disorders, which can lead to accurate diagnosis and intervention planning for success in school and at home

Standard Neuropsychiatric Inventory-Questionnaire providing a brief assessment of neuropsychiatric symptomatology in routine clinical practice settings.

Standard Neuropsychiatric Inventory-Questionnaire, analyzes the Severity of the symptoms present within the last month on a 3-point scale: 1 (mild), 2 (moderate), 3 (severe). This questionnaire analyzes also the distress on a 5-points scale described below:

0 = Not distressing at all

• = Minimal
• = Mild
• = Moderate
• = Severe
• = Extreme or Very Severe

The Geriatric Depression Scale (GDS) is a 30-item self-report assessment used to identify depression in the elderly. Patients have to answer, with YES (0 point) or NO (1 point), to the questions and the following general cutoff may be used to qualify the severity:

normal 0-9, mild depressives 10-19, severe depressives 20-30.

The cognitive Reserve Questionnaire (CRIq) is an instrument for measuring the cognitive reserve of an individual by means of the compilation of information relating to his or her entire adult life. This questionnaire analyzes the Education, Working Activity and Leisure Time with point subscales based on the years for each activity. The cognitive reserve outcome is valuated as below: low≤ 70, medium-low 70 : 84, medium 85 : 114, medium-high 115 : 130 , high ≥ 130

Bioelectrical impedance analysis (BIA)

Hand grip test

timed up and go test

Short Physical Performance Battery (SPPB)

Frailty index was developed to assess for frailty risk in older adults using items collected in existing nursing datasets. This is a questionnaire composed by 10 items and represents an assessment instrument with scores ranging from 0-10. A score of 0 indicates no frailty; a score of 1-3 indicates frailty risk; and a score of 4 or greater indicates frailty

Activities of daily living (ADL)

Instrumental Activities of Daily Living (IADL)

Measuring circulating levels of inflammation cytokines: EGF, Eotaxin, G-CSF, GM-CSF, IFNα2, IFNγ, IL-10, IL-12P40, IL-12P70, IL-13, IL-15, IL-17A, IL-1RA, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, TNFα, TNFβ, VEGF, FGF-2, TGF-α, FIT-3L, Fractalkine, GRO, MCP-3, MDC, PDGF-AA, PDGF-BB, sCD40L, and IL-9.

Measuring circulating levels of E Vitamins, Superoxide dismutase (SOD), catalase, GPx.

to evaluate the potential variations of changes in bacteria populations in the microbiota after 6 and after 12 months of treatment compared to baseline and compared to placebo.

to evaluate the potential variations of changes in short chain fatty acids levels in the microbiota after 6 and after 12 months of treatment compared to baseline and compared to placebo.

Number of Adverse events and serious adverse events that will be recorded throughout the duration of the study.