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Deprescribing antipsychotics in long-term care residents with behavioral and psychological symptoms of dementia

for 21 overlapping inflammatory markers (Figure 1C shows re-
sults for IP-10), although ceiling effects may limit MSD for
some markers (Figure 1D). We analyzed the association of these
and other markers with the ratio of CSF total-tau (t-tau)to
, a widely used index of disease progression. Even in this
limited sample, we observed significant correlation (p <0.05) be-
tween IL-1b, IL-8, IP-10, MCP-1, or TNF-a(all measurable using
both platforms) and log t-tau/Ab
(e.g., Figure 1A, 1B). MCP-4
and TARC were also correlated with log t-tau/Ab
measurable by MSD only. Conclusions: Changes in markers of
AD progression may be used in high-risk populations to assess po-
tential of candidate preventive interventions. The importance of
inflammatory processes in AD pathogenesis is suggested by a
strong association between several inflammatory markers and an
established index of AD progression. Our results suggest a ratio-
nale for testing anti-inflammatory treatments as potential preven-
tives that may delay onset of AD symptoms – now under
investigation in INTREPAD. The longitudinal pattern of individ-
ual inflammatory markers and their response to NSAID treatment
may reveal much about the etio-pathogenesis of AD.
Shijun Zhang, Jeremy E. Chojnacki, Jacob Fulp, Dong Sun, Virginia
Commonwealth University, Richmond, VA, USA. Contact e-mail: szhang2@
Background:Inflammasomes have been indicateda critical role in the
pathogenesis of Alzheimer’s disease (AD). Small molecule NLRP3
inflammasome inhibitors were developed as potential therapeutic
agents for AD. Methods: Small molecule NLRP3 inflammasome in-
hibitors were designed and synthesized. J774A.1 cells were treated
with compounds and the levels of IL-1beta were analyzed. APP/
PS1 mice were treated with compound for three months and pathol-
ogy and behavioral functions were analyzed. Results: Compound
GA3 selectively inhibited NLRP3 inflammasome, not other inflam-
masomes such as AIM2 and NLRC4. In addition, GA3 specifically
targeted the NLRP3 inflammasome complex to exhibit the observed
effects on the level of IL-1beta. In APP/PS1 mice, treatment with
GA3 significntly suppressed microglia activation and inflammation
as reflected by the reduced expression levels of inflammatory
markers ED1 and OX6. Furthermore, treatment with GA3 signifi-
cantly reduced the Abeta burden and improved the behaviroal func-
tions in Morris water maze latency and probe trial tests. APP/PS1
mice also demonstrated improved performance in novel object
recognition test and fear conditioning test after GA3 treatment. Con-
clusions:Selective NLRP3 inflammasome inhibitors have been suc-
cessfully developed and treatment of APP/PS1 mice with our
inhibitor significantly reduced AD pathologies and improved perfor-
mance in multiple behaviroal tests, suggesting that targeting NLRP3
inflammasome could be a effective strategy to develop novel thera-
peutics for AD.
MONDAY, JULY 25, 2016
Tiffany Jessop
, Fleur Harrison
, Monica Cations
, Allan Shell
Henry Brodaty
UNSW Australia, Sydney, Australia;
School of Public
Health and Community Medicine, UNSW Australia, Sydney, Australia;
University of New South Wales, Sydney, Australia.
Contact e-mail:
Background: Antipsychotic medications continue to be prescribed
for the management of Behavioral and Psychological Symptoms
of Dementia (BPSD) despite revised guidelines, tighter regulation
and evidence for the associated risks including accelerated cogni-
tive decline, stroke and death. The Halting Antipsychotic use in
Long Term care (HALT) project aimed to reduce the inappropriate
use of these medications and improve non-pharmacological
behavior management. Methods: Twenty-four long term care facil-
ities were recruited across metropolitan and regional areas. Poten-
tial participants were aged over 60 years, on regular antipsychotic
medication, without a primary psychotic illness, and without severe
neuropsychiatric symptoms as indicated by a total Neuropsychi-
atric Inventory (NPI) score above 50 and individual domain scores
at maximum for at least two of delusions, hallucinations, agitation-
aggression, anxiety, and disinhibition. Training was provided for
facility nurses on how to manage neuropsychiatric symptoms using
person-centered, non-pharmacological approaches. Consenting
participants were assessed one month and one week prior to
commencement of deprescribing. Protocols for incremental de-
creases in antipsychotic dose were established on an individual ba-
sis by project pharmacists with agreement from the participants’
GP. Participants were re-assessed 3, 6 and 12 months following
initial dose reduction. The primary outcome measure was reduction
of regular antipsychotic medication without use of substitute psy-
chotropic medications. The secondary outcome measures were
NPI total and domain scores and Cohen-Mansfield Agitation Inven-
tory (CMAI) score. Results: Of 156 residents recruited, 135 have
achieved antipsychotic cessation to date. Of these, 76% remain
off the antipsychotic medication up to 12 months following initial
reduction. NPI and CMAI scores of the first 71 participants as-
sessed 6 months after deprescribing remained stable from baseline
to follow-up. For participants where data were available, over
60% were prescribed the current antipsychotic after admission
to long term care. Conclusions: Deprescribing of antipsychotics
in long term care residents with previous BPSD is feasible
without re-emergence of BPSD; however, challenges still exist
regarding sustainability and culture of prescribing in aged care.
The impact of facility and individual factors on outcomes and rea-
sons for recommencement following deprescribing warrant
further investigation.
Podium Presentations: Monday, July 25, 2016P262
... Although antipsychotics were targeted in our study at residents with higher levels of agitation, our findings suggest that these medications had limited effect on BPSD, with proxy caregivers still rating agitation and behavioural disruption most frequently in those taking antipsychotics. The findings from a recent study undertaken in NSW, Australia, may heighten the need for a reduction in prescribing of antipsychotics in this population, as the study found no significant change in the behaviour of 75% of the 139 residents in LTC whose antipsychotic use was ceased at three, six, and 12 months [25]. ...
Full-text available
Background: Neuropsychiatric symptoms of dementia are often treated through the prescription of one or more psychotropic medications. However, limited efficacy and potential harmful side-effects has resulted in efforts to reduce the use of psychotropic medication in this population, particularly for those living in long-term care. Objectives: This study sought to describe the pattern of central nervous system medication usage in older adults with dementia living in long-term care; assess the appropriateness of prescribing against Beers criteria; and detect potential drug interactions from co-administered medications. Methods: A retrospective descriptive audit of the medical records of n=415 residents, aged >60 years with a diagnosis of dementia, from 28 long-term care facilities in Queensland, Australia. Information extracted included the types and usage of regular and Pro Re Nata central nervous system medications. Results: Of those taking medication (n=317), 68% were prescribed at least one potentially inappropriate medication, and there was a significant positive correlation between the number of medications prescribed and the number of potentially inappropriate medications. Two-hundred potential interactions with variable severity were identified from 130 residents on ≥1 medication - 38% were potentially severe interactions, 46% were moderate. Conclusions: This medication audit raises concerns that prescription of medications may still be the first resort to treat behavioural and psychological symptoms of dementia. There is a need for effective and sustainable person-centred interventions that address barriers for appropriate prescribing practice, and involve the collaboration of all healthcare professionals to optimise prescribing and improve the quality use of medicines in older people with dementia.
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