Table 1 Inclusion/exclusion criteria

1. Male or female, aged 55–95 inclusive

2. Diagnosis of MCI or mild-stage dementia presumed due to AD and AD-related disorders

3. Cognitive abilities sufficient to be able to complete all study tasks as determined by the PI or a co-investigator

4. Education level, English language skills, and literacy that indicates participant will be able to comprehend all assessments

5. Neuropsychiatric Inventory Agitation/Aggression Question 4 = “No” or “Yes” with a mild severity rating

6. Willing and able to complete all assessments and study procedures

7. Not pregnant, lactating, or of child-bearing potential

8. Volunteer has a study partner with at least 2 days per week of contact and willing to complete partner study forms

9. No exclusionary medications or dietary supplements. See Section 6.5.8.1

10. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline

11. Basic videoconferencing capabilities and a willingness to participate in a virtual trial (including self-administered ECG)

1. Any history of specific central nervous system disease other than AD/ADRDs, such as major clinical stroke, brain tumor, normal pressure hydrocephalus, multiple sclerosis, significant head trauma with persistent neurological or cognitive deficits or complaints

2. Clinically significant or unstable medical condition that could affect safety or compliance with the study and would, in the opinion of the investigator, pose a risk to the participant if they were to participate in the study

3. Major active or chronic severe psychiatric illness (e.g., major depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year

4. Current suicidal ideation or history of suicide attempt

5. History of alcohol or other substance abuse or dependence with the past 2 years

6. Clinically significant abnormalities on complete blood count, comprehensive metabolic panel, vitamin B12, or thyroid-stimulating hormone screening safety lab results

7. Concomitant use of medications with psychoactive properties that may deleteriously affect cognition (anticholinergics, antihistamines, antipsychotics, sedative hypnotics, anxiolytics)

8. Treatment with monoamine oxidase inhibitors, coumadin, phenobarbital, phenytoin, primidone, tricyclic antidepressants, or other medicines with potential for clinically significant interaction

9. Hypersensitivity to MPH

10. History of marked anxiety and agitation, ADHD, motor tics, glaucoma, or a history or family history of Tourette’s syndrome

11. Clinically significant cardiac condition for which MPH may be contraindicated as determined by study physician, such as MI or ventricular arrhythmia within 6 months of enrollment

12. History of untreated, uncontrolled hypertension or a blood pressure greater than 150/90 at screening visit

13. Use of other small molecule or device-based investigational agents 1 month prior to entry and for the duration of the trial