Online Neuropsychological Test Validation Project With Imaging Pilot

This is a five year study conducted in cooperation with the Brain Health Registry (BHR), an internet-based registry which enrolls adult volunteers in order to facilitate clinical trials for the prevention of Alzheimer's disease (AD). The investigators goal is to validate the Brain Health Registry's online cognitive measures developed by Lumosity. Investigators will meet this goal by collecting data from the newly developed the BHR online cognitive screening battery along with standardized measures of memory, attention, executive functioning and speed of information processing currently used in clinical trials for Alzheimer's disease.

This study is conducted in cooperation with the Brain Health Registry (BHR, CHR #12-09628), an internet-based registry which will enroll individuals in order to facilitate clinical trials for the prevention of Alzheimer's disease (AD) and other brain diseases and disorders.

The investigators goal is to validate the Brain Health Registry's online cognitive measures developed by Lumosity. Investigators will meet this goal by collecting data from the newly developed BHR online cognitive screening battery along with standardized measures of memory, attention, executive functioning and speed of information processing currently used in clinical trials for Alzheimer's disease.

Investigators will enroll 1000 subjects, 500 of whom will be recruited upon registering in the BHR. The other 500 subjects will be recruited from the Memory and Aging Center at the University of California, San Francisco (UCSF) and the Center for Imaging of Neurodegenerative Diseases (CIND) at the San Francisco VA Medical Center (SFVAMC). Demographic and clinical data will be obtained for each participant who will have 3 tests of cognitive function over a 2 week period: 1) unsupervised online cognitive testing, 2) supervised online cognitive testing, and 3) standard clinical neuropsychological assessments. The order in which cognitive evaluations are administered will be equally distributed within the sample so as to minimize practice effects. These subjects will also provide a saliva specimen in order to determine their ApoE genotype.

Additionally, investigators will also conduct a small pilot study of 34 subjects to obtain one 3 Tesla MRI scan and one PET scan in order to obtain feasibility data for collecting longitudinal neuroimaging studies for participants in this sample.

In addition to the main validation project and MRI/PET substudy, we will also run a substudy (n=330) that looks to validate an additional unsupervised online cognitive measure (administered via iPad application) called ReVeRe. ReVeRe, is an automated, self-administered measure of verbal memory (word list recall) that is modeled after the Rey Auditory Verbal Learning Test.

There are two substudies for ReVeRe:

ReVeRe 1 (n=250): This approximately 30 minute procedure will be administered initially during the NVP participant's clinic visit, and then will be collected remotely (by participants at home) on: (1) Day 7 after the initial clinic testing, (2) Day 21 after the initial clinic testing, and (3) ongoing at 6 month intervals through at least 18 months - for a total of 6 administrations.

ReVeRe 2 (n=80): This approximately 30 minute procedure will be administered initially 2 weeks after a follow up in-clinic visit, and then will be collected remotely in burst intervals. There will be three administrations at each time point (Day 0, 3, and 7), which will be collected every 6 months for 24 months after the in-clinic follow up visit. All participants in ReVeRe 2 will also receive an amyloid PET scan, as long as they did not already participate in the MRI/PET substudy.

Eligibility Criteria:
Inclusion Criteria:

* Adults age 60 years and older
* Fluent in English
* Able to give informed consent
* Access and the ability to use the internet

Exclusion Criteria:

* Evidence or diagnosis of dementia
* Evidence of acute or uncontrolled medical illness
* Recent history (\< 6 months) of abuse or dependence of drugs and/or alcohol
* Significant neurological disease (ex. Parkinson's disease, Epilepsy, Traumatic brain injury)

Additionally, subjects participating in the neuroimaging portion of the study, will be excluded for any of the following:

* Unable or unwilling to travel to SFVAMC and UCSF China Basin campuses for MRI and PET procedures
* Contraindications for MR exam, including claustrophobia, paramagnetic metal implants, inability to fit comfortably in MRI (BMI \< 38)
* Clinically significant hepatic, renal, pulmonary, metabolic or endocrine disturbances as indicated by history which in the opinion of the Investigator might pose a potential safety risk to the subject
* Current clinically significant cardiovascular disease. Clinically significant cardiovascular disease usually includes one or more of the following:
* Cardiac surgery or myocardial infarction within the last 4 weeks
* Unstable angina
* Acute decompensated congestive heart failure or class IV heart failure
* Current significant cardiac arrhythmia or conduction disturbance, particularly those resulting in ventricular fibrillation, or causing syncope, or near syncope
* Uncontrolled high blood pressure
* QTc \> 450 msec
* History of drug or alcohol abuse within the last year, or prior prolonged history of abuse
* Women of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception. Women of childbearing potential must not be pregnant or breastfeeding at screening.
* History of relevant severe drug allergy or hypersensitivity.
* Receiving an investigational medication under an FDA IND protocol within the last 30 days. Additionally, the time between the last dose of the previous experimental medication and enrollment (completion of screening assessments) must be at least equal to 5 times the terminal half-life of the previous experimental medication. Subjects who have ever participated in an experimental study with an amyloid targeting therapy (e.g., immunotherapy, secretase inhibitor) may not be enrolled without prior sponsor approval unless it can be demonstrated that the patient received only placebo in the course of the trial.
* Current clinically significant unstable medical comorbidities, as indicated by history that pose a potential safety risk to the subject
* Receiving a radiopharmaceutical for imaging or therapy within the past 24 hours prior to the imaging session for this study
* Opinion of the Investigator that the subject is otherwise an unsuitable for study