A Phase II randomised, double-blind, placebo-controlled trial of S-Adenosyl Methionine (SAMe) in participants with mild cognitive impairment or dementia due to Alzheimer’s disease

INTERVENTION: 400mg S‐adenosyl methionine, oral capsules, once daily for 6 months. Drug accountability will be monitored to ensure compliance at every visit. CONDITION: Alzheimer's disease;Mild Cognitive Impairment; ; Alzheimer's disease ; Mild Cognitive Impairment Mental Health ‐ Other mental health disorders Neurological ‐ Alzheimer's disease PRIMARY OUTCOME: Cerebrospinal fluid levels of p‐tau assessed via lumbar puncture (spinal tap).[Screening and six months (primary endpoint). ] SECONDARY OUTCOME: Cognitive function assessment by ADAS‐Cog 13.[Screening, 3 months, and six months (secondary endpoint). ] Epigenetic changes in DNA methylation. [Screening and six months (secondary endpoint). ] Safety assessment via the presence or absence of AE's and SAE's, assessed via participant or study partner self‐report, physical examination, vital sign measurement and clinical safety blood testing at all visits. ; ; Known/possible adverse events of SAMe drug may include agitation, anxiety, irritation, and restlessness and the potential to trigger bipolar episodes. There is also a theoretical risk of serotonin syndrome if combined with anti‐depressant medications. As such, the study specifically excludes enrolment of individuals with a history of bipolar affective disorder, recent unstable psychiatric condition, or concurrent antidepressant intake.[Screening, Randomisation, 1 month, 3 months, six months, follow up (2 weeks post‐treatment).] INCLUSION CRITERIA: 1. Male and female participants aged 60 years and above at the time of signing the informed consent. 2. Participants who have mild cognitive impairment or dementia due to Alzheimer’s disease, according to the NIA‐AA 2011 criteria. 3. Participants who have a standardised mini‐mental state examination (sMMSE) score of 20 or above. 4. If using medications to treat symptoms of AD (e.g. donepezil), doses must be stable for at least 8 weeks prior to screening. 5. CSF profile at screening consistent with a profile of AD as defined by Collins et al. 6. Agreeable to undergo lumbar puncture at screening and 6‐months. 7. Living at home or in a community setting (assisted living) without continuous nursing care. Each subject must have a reliable caregiver or study partner who sees them at least 3 times weekly, can oversee the administration of study drug, and is willing and able to participate in all clinic visits and some study procedures. The respon