Cognitive brain circuits and the spread of tau in vivo in humans

Prior treatment

• Women of childbearing potential. Female subjects who are of childbearing potential are eligible to participate if they use a highly effective method of contraception that is either user-dependent (combined (estrogen- and progestogen-containing) hormonal contraception or progestogen-only hormonal contraception associated with inhibition of ovulation) or user-independent (implantable progestogen-only hormonal contraception associated with inhibition of ovulation), vasectomized partner or sexual abstinence). Female subjects are not considered of childbearing potential if they are surgically sterile (hysterectomy or bilateral salpingectomy/oophorectomy), or postmenopausal for at least 1 year prior to screening (defined as no menses for more than 12 months without an alternative medical cause).
• Female partner of male subjects must be surgically sterile (hysterectomy or bilateral salpingectomy/oophorectomy or bilateral tubal occlusion/ligation) or postmenopausal for at least 1 year prior to screening.

Other illness

• Participants with significant medical, neurological or psychiatric comorbidity
• Individuals with a history of epilepsy or a known family history of epilepsy will be excluded from the 40 Hz stimulation paradigm

Other

• Patients who are unable to provide written informed consent
• Structural lesions on MRI, such as large-vessel strokes, sequellae of macrohemorrhages, arachnoidal cysts, and posttraumatic lesions, will be an exclusion criterion. White matter lesions will be allowed.

• 40 patients with mild to moderate clinically probable AD according to the National Institute of Aging (NIA)-Alzheimer's Association (AA) diagnostic criteria [22], and an MMSE of 16 or higher and a Clinical Dementia Rating scale total score of 0.5 or 1.
• 40 patients with amnestic MCI due to AD according to the NIA-AA diagnostic criteria [3], an MMSE 25 or higher, and a Clinical Dementia Rating scale total score of 0.5.
• 40 amyloid-positive cognitively intact healthy controls, recruited via a longitudinal community-recruited cohort that is followed at the Laboratory for Cognitive Neurology (see below) (mean age = 68.4 6.4, range 55-80 years).
• 40 matched amyloid-negative cognitively intact healthy controls. These subjects will be matched in age, education and gender to the three first cohorts.