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Transcript of Sim Vast at in Ppt
8/6/2019 Sim Vast at in Ppt
http://slidepdf.com/reader/full/sim-vast-at-in-ppt 1/38
Simvastatin
isAssociatedwith a
ReducedIncidence of
Dementiaand
Parkinson·sDisease(A journal
report)
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BACKGROUND OF THE STUDY
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� Dementia is one of the major public healththreats that individuals face as they age.
� Dementia is a loss of brain function that occurs
with certain diseases. It affects memory, thinking,language, judgment, and behavior.
� Most types of dementia are nonreversible(degenerative). Nonreversible means the changes
in the brain that are causing the dementia cannotbe stopped or turned back. Alzheimer's disease isthe most common type of dementia.
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� Lewy body disease is a leading cause of dementia inelderly adults. People with this condition haveabnormal protein structures in certain areas of thebrain.
� The following medical conditions also can lead todementia:
� Parkinson's disease
� Multiple sclerosis
� Huntington's disease� Infections that can affect the brain, such as HIV/AIDS
and Lyme disease
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� Epidemiological studies suggest that
cardiovascular disease, hypercholesterolemia,
hypertension and diabetes are important risk
factors for the development of dementia.
� Initial studies by the researcher suggested that
statins might be beneficial as a therapy for
dementia.
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Continuation of the Study
� Two-wave epidemiological studies examined
the effects of statins on incident Alzheimer's
disease (AD), but failed to show a statistical
benefit associated with statin use .
� The number of subjects on statins who
developed incident AD in these two-wave
studies was only in the single digits
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� Two studies were also performed to
investigate whether statins might delay the
progression of cognitive decline in subjects
with mild to moderate AD which both of these
studies were quite promising because they
showed reduced progression of measures of
cognitive function
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� The cumulative review of these various
studies leads to a mixed picture, with multiple
studies both suggesting and refuting that
statins might reduce the incidence or
progression of AD.
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� In this study, the use of existing information
within this database to obtain prospective
data that allowed us to test the hypothesis
that use of statins is associated with a reduced
incidence of dementia
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METHODS:
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DATABASE
EXCLUSION CRITERIA AND
RESTRICTIONS
COMPARATORS/MODELS
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� DATABASE
The researcher restricted out study to the years
20032005 to allowed tracking of prescription usage for every subject.
This strategy also allowed 2002 to be used as a
baseline period for the study to ensure that
the subjects did not have a prior diagnosis of
AD and PD
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� EXCLUSION CRITERIA AND RESTRICTIONS
� Analysis was restricted to subjects 65 years
of age, who did not have a prior diagnosis of AD
� For the studies of Parkinson's disease (PD), a
prior diagnosis of PD was an exclusion
criterion.
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� Subjects selected for further analysis were alsothose who had 7 months of continual use of statins after initiation of pharmacotherapy (a
time period that refer to as the treatmentwindow), without diagnosis of AD during thisperiod.
� Continual use was defined by the presence of
repeat prescriptions refills during the 7-monthtime period, with gaps in prescription refills thatwere of no more than 6 weeks in duration.
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� Subjects were analyzed for continual use of
medication only during the first 7 months of
analysis. A similar approach was used for
establishing newly acquired Parkinson's
disease.
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� COMPARATORS/MODELS
- Two different approaches were used to identifyreference groups as comparators for the analyses
of subjects taking statins.- age distribution of each comparator group was
matched to that of the statin group by identifyingrecords of subjects 65 years of age, dividing the
subjects into decades (6574, 7584, 8594, 95)and determining the proportion of subjects ineach age group.
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� Cardiovascular com parator
� Cardiovascular comparator were used as theprimary comparator because many statin
users have comorbid cardiovascular disease.
� Warfarin was used as a secondary comparatorto allow comparison to a specific medication,
because use of one identified medicationfacilitates assessment of potential modifyingfactors.
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Statistical Analysis
� Kaplan-Meier survival curves were plotted to
show the rate of events
� Cox proportional hazards models were used to
estimate the association between exposure to
statins and risk of dementia
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RESULTS
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� 4 Major Results:
a.C
haracterization of records from DSSdatabase
b. Cumulatative incidence curves for each statins
using CV comparator and adjusted for
covariates using hazard rates by COX
proportional hazard method.
c. Statistical parameters describing # of cases
and censorship.
d. Analysis of the effect of the statins on
incidence of Parkinsons disease using Cox
proportional advance survival method
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A. Characterization of records from DSS
database
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B. Cumulative Incidence Curves
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C. Statistical Parameters describing the # of
Cases and censorship
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D. Analysis of the incidence of Statins on
incidence of PD
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DISCUSSION
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Previous Studies
*produced mixed results- Differences in efficacy of statins
- Variations in responses in the population
- Inadequate sample size
this study used very large population database
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Large number of subjects
- Provides enormous power for analyses- Subcategorization of the cohorts
- Allows for prospective studies of incidence
Division of statin users to each statin
-allow the examination of the effects of different
statins (atorvastatin, lovastatin,simvastatin)
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Ability to track subjects over a period of time
-allowed the examination of incident dementiacases
-could explain the differences from the previous
study (prevalent cases)
Covariates (HPN,DM,CVD)
- provide some adjustment for confounding
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Prospective study vs RCT
-subjects in population databases have
comorbid illnesses
- RCT can control the type or degree of comorbid illness or exclude subjects with
comorbid illnessess
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� 2 comparators :
a. CV comparator-many statin users have comorbid
cardiovascular disease
b. Warf arin
-to allow comparison to a specific medication
(DVT, stroke,AF)- do not modify the course of dementia
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DSS Database
-does not provide laboratory values and imaging
studies
-can¶t determine the degree of cholesterol
reduction associated with each statin
-can¶t quantify cognition
-do not meet NINDS-ARDA criteria for AD
-misdiagnosis dementia
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Simvastatin
-reduction of incidence of dementia is striking
-biological action vs statistical bias
-Previous studies: it is more effective in modifying
some measures of lipid metabolism
-better in raising HDL
-strong efficacy and intermediate permeability to
bbb
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Simvastatin
-Unique pharmacologic profileliphopilicity and
efficacy
-efficacy towards PD (common mechanism)
Statins
-reduce inflammation, osteoporosis, fractures
and diseases caused by heart disease
(+) AD pathology: less inflammation
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