DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study.
OBJECTIVE
To compare the efficacy and tolerability of dehydroepiandrosterone (DHEA) vs placebo in AD.


METHODS
Fifty-eight subjects with AD were randomized to 6 month's treatment with DHEA (50 mg per os twice a day; n = 28) or placebo (n = 30) in a multi-site, double-blind pilot trial. Primary efficacy measures assessed cognitive functioning (the AD Assessment Scale-Cognitive [ADAS-Cog]) and observer-based ratings of overall changes in severity (the Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus]). At baseline, 3 months, and 6 months, the ADAS-Cog was administered, and at 3 and 6 months, the CIBIC-Plus was administered. The 6-month time point was the primary endpoint.


RESULTS
Nineteen DHEA-treated subjects and 14 placebo-treated subjects completed the trial. DHEA was relatively well-tolerated. DHEA treatment, relative to placebo, was not associated with improvement in ADAS-Cog scores at month 6 (last observation carried forward; p = 0.10); transient improvement was noted at month 3 (p = 0.014; cutoff for Bonferroni significance = 0.0125). No difference between treatments was seen on the CIBIC-Plus at either the 6-month or the 3-month time points.


CONCLUSIONS
DHEA did not significantly improve cognitive performance or overall ratings of change in severity in this small-scale pilot study. A transient effect on cognitive performance may have been seen at month 3, but narrowly missed significance.
Wolkowitz
O M
OM
Department of Psychiatry, Center for Neurobiology and Psychiatry, University of California San Francisco (UCSF) School of Medicine, USA. owenw@itsa.ucsf.edu
Kramer
J H
JH
Reus
V I
VI
Costa
M M
MM
Yaffe
K
K
Walton
P
P
Raskind
M
M
Peskind
E
E
Newhouse
P
P
Sack
D
D
De Souza
E
E
Sadowsky
C
C
Roberts
E
E
D000368:Aged; D017109:Akathisia, Drug-Induced / Q000209:etiology; D000544:Alzheimer Disease / Q000188:drug therapy*; D003071:Cognition / Q000187:drug effects; D003221:Confusion / Q000139:chemically induced; D003687:Dehydroepiandrosterone / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use; D010259:Paranoid Disorders / Q000139:chemically induced; D010352:Patient Dropouts; D010865:Pilot Projects; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D018697:Nootropic Agents; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone