Featured Research Sessions: F4-02: Treatment Strategies for Psychosis and Agitation in Alzheimer’s DiseaseP608

hippocampal volume, APOE-ε4 status) in early MCI and MCI subjects en-

rolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A subset

of these subjects was followed longitudinally prior to amyloid imaging,

which allowed us to evaluate which markers were linked to conversion

fromMCI to AD and longitudinal cognitive decline.Results:Amyloid pos-

itivity increased with disease severity, with approximately 40-60% of early

MCI and MCI subjects showing substantial florbetapir uptake, compared

with approximately 30% of normal subjects and 80% of AD patients. In

early MCI, florbetapir was moderately associated with FDG but closely

linked to concurrent memory function, whereas the reverse was true for

MCI, where florbetapir was strongly related to FDG but only moderately as-

sociated with memory function. During follow-up, nearly 50% of MCI sub-

jects converted to AD. Atrophy, FDG-PET, amyloid, and APOE status were

all useful in predicting conversion status and cognitive decline. However,

differences in biomarkers were more evident in models that tracked longi-

tudinal decline rather than conversion, perhaps because continuous mea-

sures of cognitive function make it possible to examine incremental

changes in function from the subject’s own baseline. Conclusions: Associ-

ations between amyloid and cognitive function may be stronger in the ear-

liest phases of disease (normal and early MCI individuals) despite minimal

cognitive dysfunction in these populations. In MCI, hypometabolism may

be more directly linked than amyloid to cognitive ability. These findings

support a model in which amyloid deposition is associated with the earliest

stages of subtle cognitive impairment, followed by metabolic, synaptic, and

structural dysfunction that parallels further cognitive decline. Tracking fu-

ture (prospective) changes in cognitive function and other biomarkers will

be critical for determining the predictive role of amyloid imaging.

FEATURED RESEARCH SESSIONS: F4-02

TREATMENT STRATEGIES FOR PSYCHOSIS AND

AGITATION IN ALZHEIMER’S DISEASE

F4-02-01 PRESCRIBING DRUGS FOR PSYCHOSIS AND

AGITATION MAY CAUSE MORE HARM THAN

GOOD: A SYSTEMATIC REVIEW OF

EFFECTIVENESS, EXPERT OPINION AND

SOCIETAL CONCERN

Figure 1. Flow Sheet for Study

Lon Schneider,University of Southern California, Los Angeles, California,

United States.

Background: The vast majority of people with Alzheimer disease and other

dementia show agitation, delusions, aggression, and other disruptive behav-

iors during their illness; and suffer and cause great distress because of them.

Most patients with disruptive behaviors are prescribed psychotropics, pre-

sumably as attempts to ameliorate their problems. Researchers and govern-

ments have cautioned that the drugs may be both ineffective and dangerous.

Methods: Review efficacy/effectiveness evidence for antipsychotics, anti-

convulsants, and antidepressants. Review expert and committee recommen-

dations, (e.g., the APA, ACNP, AAN, Alzheimer’s Association, California

Alzheimer Association, industry, regulatory organizations, and continuing

medical education).Results: The target symptoms and circumstances under

which the drugs are used are vaguely described. Individual clinical trials

generally do not show meaningful efficacy. Pooling trials reveals statisti-

cally significant modest effects for two antipsychotics and considerable

adversity for the range of psychotropics. There is lack of evidence for

long-term use even though the drugs are often used in this manner. Well-

known adverse effects for antipsychotics include mortality, cardiovascular

events, and sedation. Other drugs show substantial toxicity as well. Ob-

served reduction in symptoms may be due to the soporific suppression of ex-

pressive behaviors. Expert panels tend to cautiously recommend the drugs,

particularly antipsychotics, less so SSRIs; and antidepressants are pre-

scribed more frequently than antipsychotics. Cholinesterase inhibitors and

memantine are also ineffective for disruptive behaviors but have a better

safety profile. There is a lack of data supporting other classes of medica-

tions. Conclusions: The causes of these pleomorphic behaviors are not

known even as their antecedents are and interventions can be made. Misin-

terpretation of trials outcomes may lead to poor medical practice. Short term

use of antipsychotics and possibly other classes may help; longer use not.

Despite the many trials and consensus panels there is overall limited infor-

mation to inform physicians and patients beyond their potential for harm.

Drug companies have pled guilty to fraud with respect to the drugs; and

some law enforcement workers interpret their use in the elderly as assault

with a deadly weapon subject to prosecution. As we try to develop treat-

ments for AD we need to attend to societal concerns.

F4-02-02 RELAPSE RISK AFTER DISCONTINUATION OF

RISPERIDONE TREATMENT IN ALZHEIMER’S

DISEASE

Davangere Devanand1, Susan Schultz2, Jacobo Mintzer3, David Sultzer4,

Danilo de la Pena5, Sanjay Gupta6, Gregory Pelton7, Corbett Schimming8,

Bruce Levin1, 1Columbia University College of Physicians and Surgeons,

New York, New York, United States; 2University of Iowa, Iowa City, Iowa,

United States; 3Medical University of South Carolina, Charleston, South

Carolina, United States; 4Brentwood VA, Los Angeles, California, United

States; 5Research Center for Clinical Trials, Norwalk, Connecticut, United

Sates; 6University of Buffalo, Buffalo, New York, United States; 7Columbia

University Medical Center, New York, New York, United States; 8University

of New Mexico, Albuquerque, New Mexico, United States.

Background: In patients with Alzheimer’s disease (AD) who respond to an-

tipsychotic treatment of psychosis and/or agitation/aggression, the risk of

relapse after discontinuation is not established. Methods: AD patients

with psychosis and/or agitation/aggression received 16 weeks of open ris-

peridone treatment (phase A). Responders were then randomized, double-

blind, to one of three arms in phase B: (1) continuation risperidone for 32

weeks, (2) risperidone for 16 weeks followed by placebo for 16 weeks,

(3) placebo for 32 weeks. The primary outcome was time to relapse of psy-

chosis/agitation. Results: In phase A, 180 patients received risperidone