Trial of Carvedilol in Alzheimer's Disease

The purpose of the study is to measure decline in episodic memory in participants with early
AD taking carvedilol compared to placebo treatment as evidenced by the Hopkins Verbal
Learning Test (HVLT). cerebrospinal fluid levels of Aβ oligomers in early AD, will be
measured in participants receiving carvedilol treatment when compared to placebo treatment.
Adverse effects will be monitored in participants receiving carvedilol when compared to
placebo.

To assess adverse events, routine chemistry and hematology studies, vital signs, and
electrocardiographic parameters before and after 6 months randomized placebo-controlled
double-blind treatment with carvedilol at a target dose of 25 mg daily, comparing 25 early AD
participants taking carvedilol vs. 25 early AD participants taking placebo.

Inclusion Criteria:

- Diagnosis of AD by the National Institute of Neurological and Communicative Disorders
and Stroke and the Alzheimer's Disease and Related Disorders Association
(NINCDS/ADRDA) criteria

- Mini-Mental State Exam (MMSE) 16-26. This range corresponds roughly to "mild" AD as
rated by CDR below, and provides a rapid test for efficient screening of potential
participants.

- Clinical Dementia Rating (CDR) < 1 (mild dementia). This corresponds with "early" AD.
Participants will be eligible if they have AD diagnosis and CDR of 0.5 or 1.0. The
category of CDR 0.5 AD is particularly important to include as these participants are
in the earliest stage that can be diagnosed as dementia (as opposed to mild cognitive
impairment) and thus are in the "earliest" clinical stage of AD.

- Patients will be allowed to remain on current FDA-approved Alzheimer's treatments
including cholinesterase inhibitors and memantine, so long as the dose has been stable
for >= 3 months. These medications lack any notable effects on amyloid synthesis or
metabolism and thus there is no reason to exclude them. The rationale behind requiring
a stable dose is so that change in the trial can be attributed to the study
intervention rather than recent changes of other medications affecting cognition.

- Patients will be allowed to remain on antidepressant and antipsychotics medications so
long as the dose has been stable for >= 3 months. The rationale is the same as above.

- Knowledgeable informant available for all study visits. This is standard practice in
AD research because many standard instruments and questionnaires in this trial require
a knowledgeable informant.

Exclusion criteria

- Evidence of non-AD dementias including Huntington's disease, Parkinson's disease, or
frontotemporal dementia.

2.Current Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)-IV Axis I
diagnoses other than dementia, including major depression, bipolar disorder,
schizophrenia, anxiety disorders, alcohol abuse, or other substance abuse. These
diagnoses would merit their own treatment plans and changes in these conditions could
significantly affect cognitive and functional outcomes, confounding our efforts to
study the efficacy of the study intervention.

- Any clinically significant medical condition that could interfere with the subject's
ability to safely participate in the study or to be followed.

- Current use of Beta-blocking agents.

- Contraindications to use of Beta-blocking agents, to be determined in consultation
with the patient's primary care physician or (if appropriate) cardiologist.

- Clinically significant hepatic or renal insufficiency.