Sim Vast at in Ppt

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Simvastatin

isAssociatedwith a

ReducedIncidence of

Dementiaand

Parkinson·sDisease(A journal

report)



BACKGROUND OF THE STUDY



� 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.



� 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



� 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.



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



� 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



� 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.



� 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



METHODS:



DATABASE

EXCLUSION CRITERIA AND

RESTRICTIONS

COMPARATORS/MODELS



� 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



� 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.



� 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.



� 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.



� 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.





� 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.



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



RESULTS



� 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



A. Characterization of records from DSS

database



B. Cumulative Incidence Curves





C. Statistical Parameters describing the # of

Cases and censorship





D. Analysis of the incidence of Statins on

incidence of PD





DISCUSSION



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



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)



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



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



� 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



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



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



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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