Disruptive agitation frequently emerges as a troublesome and often chronic clinical problem during the course of Alzheimer's disease (AD). It dramatically increases caregiver burden in both home and long term care settings, is distressing to patients and others in the patient's environment, and is a common precipitant of long-term care placement. Current psychopharmacologic approaches to agitation in AD and related dementing disorders, particularly the widely-prescribed antipsychotics, are of limited demonstrated efficacy and are associated with substantial adverse effects. The latter include increased risk for stroke and death, excessive sedation and pseudoparkinsonism. The development of more effective and safer pharmacologic approaches to the treatment of disruptive agitation in AD is an important clinical goal. Neurobiologic studies in the clinic and in postmortem brain tissue provide rationale for involvement of enhanced central nervous system (CNS) responsiveness to norepinephrine (NE) at the alpha-1 adrenoreceptor (AR) in the pathophysiology of disruptive agitation in AD. Our preliminary placebo-controlled clinical trial feasibility data support potential efficacy of the generically available brain active alpha-1 AR antagonist, prazosin for agitation in AD and good tolerability of this drug in this elderly and often frail population. We propose a placebo-controlled trial of prazosin, for disruptive agitation in AD.

Public Health Relevance

Agitation in dementia is a major cause of morbidity and excess disability. It places great burden on caregivers and is probably the most common precipitant of long term care placement. Demonstrating an effective and well tolerated medical treatment for this problem would be a great benefit.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program--Cooperative Agreements (U19)
Project #
4U19AG010483-25
Application #
8982203
Study Section
Special Emphasis Panel (ZAG1-ZIJ-7)
Project Start
Project End
Budget Start
2015-12-01
Budget End
2016-11-30
Support Year
25
Fiscal Year
2016
Total Cost
$1,376,601
Indirect Cost
$56,354
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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