Alzheimer's Disease THErapy With NEuroaid II

Alzheimer's Disease Assessment Scale-Cognitive Subscale11 (ADAS-Cog11)

The ADAS-Cog is a rater-administered instrument designed to assess the severity of cognitive impairment and associated non-cognitive behaviors characteristic of individuals with AD. It is the most widely used cognitive scale in clinical trials evaluating treatments for mild to moderate AD. For this study, the version of ADAS-Cog11 will be used as the primary efficacy assessment. The ADAS Cog11 consists of 11 items assessing key areas of cognitive function that are commonly impaired in AD, including: orientation, word recall, word recognition, remembering word recognition test instructions, commands, comprehension of spoken language, naming, word-finding difficulty, spoken language ability, construction praxis, and ideational praxis. The ADAS-Cog11 total score ranges from 0 to 70, with higher scores indicating greater cognitive impairment.

Clinical Dementia Rating (CDR): Global Score and Sum of Boxes (CDR-SB)

The CDR evaluates both cognitive and functional domains through structured interviews conducted with both the participant and a knowledgeable informant (such as a caregiver or study partner). The assessment is administered by a trained assessor according to a standardized protocol. The CDR includes the following 6 domains: 3 cognitive domains (memory, orientation, and judgment/problem solving) and 3 functional domains (community activities, home and leisure, and personal care). Each domain is rated on a scale from 0 (no impairment) to 3 (severe impairment). The CDR yield 2 scores, including CDR Global Score and CDR-SB. The CDR global score: a categorical rating from 0 to 3, derived via a standardized algorithm. This score is used to stage the severity of dementia as follows: 0= No dementia; 0.5= Very mild dementia; 1= Mild dementia; 2= Moderate dementia; 3= Severe dementia. CDR-SB: a continuous score ranging from 0 to 18, calculated by summing the individual domain scores.

Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)

The ADCS-ADL, developed by Galasko et al, is the most widely used instrument for assessing functional outcomes in patients with AD. This 23-item scale evaluates both basic activities of daily living-such as eating and toileting-and more complex instrumental activities of daily living. The ADCS-ADL is administered as a structured interview with the participant's study partner or caregiver. For each item, the study partner is first asked whether the participant attempted the activity within the past four weeks. If so, the study partner is then asked to describe the participant's performance, which is scored accordingly. The total ADCS-ADL score ranges from 0 to 78, with lower scores indicating greater functional impairment.

Neuropsychiatric Inventory (NPI)

The NPI is a validated instrument developed to assess a broad spectrum of behavioral and psychological symptoms commonly observed in individuals with dementia. The purpose of the NPI is to characterize the presence and severity of these symptoms. The questionnaire assesses 12 neuropsychiatric symptom domains: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, aberrant motor behavior, nighttime disturbances, and appetite/eating abnormalities. For each symptom domain, both frequency and severity are assessed. Severity is rated on a 3-point scale (mild, moderate, or marked), while caregiver distress related to each symptom is also rated on a 6-point scale (ranging from no distress to very severe distress). The NPI is administered via a structured interview with the subject's study partner or caregiver, who provides observations based on the subject's behavior.

Adverse events

Listing and calculating the number and percentage of subjects experiencing non-serious and serious adverse events for each arm.

Plasma biomarkers - phosphorylated tau (p-tau217)

Plasma samples will be collected from all subjects and used for research purposes to identify dynamic biomarkers that may be predictive of treatment response to MLC901. During screening, at baseline and subsequent visits as detailed in the Schedule of Events, whole blood samples will be obtained from every subject who has consented to participate in the study. The plasma samples will be used to evaluate p-tau217 in pg/mL.

Plasma biomarkers - neurofilament light chain (NfL)

Plasma samples will be collected from all subjects and used for research purposes to identify dynamic biomarkers that may be predictive of treatment response to MLC901. During screening, at baseline and subsequent visits as detailed in the Schedule of Events, whole blood samples will be obtained from every subject who has consented to participate in the study. The plasma samples will be used to evaluate NfL in pg/mL.

Plasma biomarkers - glial fibrillary acidic protein (GFAP)

Plasma samples will be collected from all subjects and used for research purposes to identify dynamic biomarkers that may be predictive of treatment response to MLC901. During screening, at baseline and subsequent visits as detailed in the Schedule of Events, whole blood samples will be obtained from every subject who has consented to participate in the study. The plasma samples will be used to evaluate GFAP in pg/mL.