Alzheimer S Disease Phenotype

Dementia and Alzheimer’s Disease Phenotype Pseudocode April 7, 2008

Alzheimer’s Disease Research Quality Phenotype Does anyone in the group other than Group Health have this quality information? The first target phenotype that we will analyze in the ADPR/ACT population is probable or possible AD based on NINCDS-ADRDA criteria.

A 2-stage screening process is used to identify cases; CASI scores ≤85 prompt a dementia evaluation (in HAAS the CASI cut point is 74). Informant, subject, or staff reports of cognitive difficulties also trigger evaluation. The 2nd stage diagnostic examination has two parts: neuropsychological testing and a neurological exam by a physician. Medical records are abstracted for standardized labs (CBC, chemistry panel, B12, TSH) and neuroimaging. If any of these are unavailable in the prior year they are obtained. These data are used to complete standard DSM-IV diagnostic criteria for dementia and subtypes, NINCDS-ADRDA criteria for AD, and 3 sets of criteria for vascular dementia. The dementia neuropsychological battery includes clock drawing, verbal fluency, Mattis Dementia Rating Scale, Boston naming, verbal paired associations and recall, logical memory and recall, Word List Memory, Constructional Praxis and recall, Trails A and B, and Information and Comprehension subtest items. All clinical data are reviewed at a consensus conference. These procedures have been used continuously over 22 years since the inception of the ADPR in 1986. ACT dementia and AD diagnoses have been used in many papers, including an incidence rate paper, and high-impact papers on exercise, cholesterol, statins, and vitamins. Of note, in the first 221 ACT subjects who died and came to post-mortem examination, clinical diagnoses during life of probable AD and possible AD were equally likely to be found to have high-grade plaques and tangles: for probable AD, 18/33 (55%) had both Braak stage >=4 AND CERAD score >=2, while for possible AD these numbers were 10/19 (53%). The distribution of Braak stages was similar for the two groups.

Case = Probable/possible Alzheimer’s disease adjudicated by a consensus panel

Each case reviewed by a consensus panel that includes:  The examining MD  A second MD who is either a neurologist or geriatrician  A neuropsychologist  A psychometrician  The study RN

Criteria Used by panel: 1. Meets DSM IV – Dementia criteria 2. NINCDS-ADRDA criteria for probable and possible Alzheimer’s. 3. Study also has an autopsy “bank” (relevant for diagnosis of definite Alzheimer’s) and approximately 1,200 consents for autopsy from currently living participants.

Dementia Clinical Quality Phenotype

Identify Dementialusing an ICD-9 DX codes ora drug from the following list: Tacrine (Cognex), donepezil (Aricept, Eisai Inc. and Pfizer Inc.), galantamine (Razadyne, also called Reminyl prior to April 2005, Ortho-McNeil Neurologics, US), rivastigmine (Exelon, ExelonPatch, Novartis Pharmaceuticals Corporation), memantine (Namenda)."

The VDW program we propose is: title "Identify people with Demential including Alzheimber's Disease using clinical DX and Drugs";

%let StartDt = 01jan2000 ; %let EndDt = 31dec2007 ;

* Get those with Alzheimer's DX code; ************************************; data DxCodes ; input Dx $char6. ; cards; 290.0 Senile dementia, uncomplicated 290.10 290-10-290.13Presenile dementia 290.11 290.12 290.13 290.20 senile dementia delusionial [paranoid] features 290.21 senile dementia with depressive features 290.3 senile dementia with delirium or confusion 290.40 290.40-290.43 arteriosclerotic dementia 290.41 Vascular dementia with delirium 290.42 Vascular dementia with delusions 290.43 291.0 291.0-291.2 dementia due to alcohol 291.1 291.2 292.82 dementia due to drugs 294.10 294.10-294.11 dementia not classified as senile, presenile, or arteriosclerotic 294.11 331.0 Alzheimer's disease 331.11 Pick's disease of the brain 331.19 Other frontotemporal dementia 331.82 Dementia with Lewy bodies. Dementia with Parkinsonism run; * comment for 5 digit codes do we need to expand to 6? i.e. 291.0x? ;

%GetDxForDx( DxCodes /* The name of a dataset containing the diagnosis list you want. */ , Dx /* The name of the DX variable in DxLst */ , &StartDt /* The date on which you want to start collecting fills. */ , &EndDt /* The date on which you want to stop collecting fills. */ , AlzDxPeople /* The name of the output dataset containing the fills. */ ) ; run;

* Get Alzheimer's drugs from RX; **************************; data NdcCodes; input ndc $char11. ; cards; 000071009625 NDC for "Tacrine 10 MG Oral Capsule": 000071009640 00071009625 00071009640 00143910812 059630019012 59630019012 000071009725 NDC for "Tacrine 20 MG Oral Capsule": 000071009740 00071009725 00071009740 00143910912 059630019112 59630019112 000071009525 NDC for "Tacrine 30 MG Oral Capsule": 000071009540 00071009525 00071009540 00143911012 059630019212 59630019212 000071009825 NDC for "Tacrine 40 MG Oral Capsule": 000071009840 00071009825 00071009840 00143911112 059630019312 59630019312 000143-9108-12 NDC for "Cognex 10 MG Oral Capsule": 00071009625 00071009625 00071009640 00071009640 00143910812 059630-*190-12 59630-190-12 59630019012 59630019012 62856085130 NDC for "donepezil 1 MG/ML Oral Solution": 062856083230 NDC for "donepezil 10 MG Disintegrating Tablet": 49999075430 62856083230 00247181930 NDC for "donepezil 10 MG Oral Tablet": 00247181960 00615552305 00615552331 00615552339 011071-*832-01 011071-*842-01 062856024630 062856024641 11071083201 11071084201 12280036715 12280036730 12280036790 26053012201 51129412601 51129412602 54868424500 55289015121 55289015130 58864089530 62856024611 62856024617 62856024630 62856024641 62856024690 66105073701 66105073703 66105073706 66105073709 66105073715 67544009215 67544009231 67544009288 67544009289 011071-*831-01 NDC for "donepezil 5 MG Disintegrating Tablet": 062856083130 11071083101 49999075330 62856083130 00247181830 NDC for "donepezil 5 MG Oral Tablet": 00615552905 00615552931 00615552939 011071-*841-01 062856024530 062856024541 11071084101 12280029215 12280029230 12280029290 26053012101 54868395200 55154245000 58864088630 62584017750 62856024507 62856024511 62856024530 62856024541 62856024547 62856024567 62856024590 66105073901 66105073903 66105073906 66105073909 66105073915 67544059231 00615652631 NDC for "Galantamine 12 MG Oral Tablet": 00615652639 050458039260 050458039860 21695059130 50458039260 50458039860 59604039260 59604039860 62579039260 050458038830 NDC for "Galantamine 16 MG Extended Release Capsule": 50458038804 50458038830 59604038804 59604038830 050458038930 NDC for "Galantamine 24 MG Extended Release Capsule": 50458038930 59604038930 000179-1721-70 NDC for "Galantamine 4 MG Oral Tablet": 000179-1721-71 000179-1721-72 00179172170 00179172171 00179172172 00615652531 00615652539 050458039060 050458039660 12280029160 21695018430 26053015501 50458039004 50458039060 50458039660 51129332501 51129332502 59604039060 59604039660 61392055925 61392055930 61392055960 62579039040 62579039060 050458039910 NDC for "Galantamine 4 MG/ML Oral Solution": 12578039910 12578049010 50458039910 50458049010 050458038730 NDC for "Galantamine 8 MG Extended Release Capsule": 50458038704 50458038730 59604038704 59604038730 00615651731 NDC for "Galantamine 8 MG Oral Tablet": 00615651739 050458039160 050458039760 26053015601 50458039104 50458039160 50458039760 51129332901 51129332902 59604039104 59604039160 59604039765 62579039160 000078050115 NDC for "24 HR rivastigmine 0.192 MG/HR Transdermal Patch": 00078050115 00078050161 17088010401 59568050101 000078050215 NDC for "24 HR rivastigmine 0.396 MG/HR Transdermal Patch": 00078050215 00078050261 0078-0502-15 17088010501 59568050201 000078032306 NDC for "rivastigmine 1.5 MG Oral Capsule": 000078032308 000078032344 00078032306 00078032308 00078032315 00078032326 00078032344 055111-*352-01 055111-*352-05 055111-*352-30 055111-*352-60 12280038960 17088001801 26053029901 54868451200 54868451201 55111035201 55111035205 55111035230 55111035260 66544000401 66828001201 000078033931 NDC for "rivastigmine 2 MG/ML Oral Solution": 00078033931 000078032406 NDC for "rivastigmine 3 MG Oral Capsule": 000078032408 000078032444 00078032406 00078032408 00078032415 00078032444 00615136531 00615136539 055111-*353-01 055111-*353-05 055111-*353-30 055111-*353-60 17088001901 17856032402 26053030001 55111035301 55111035305 55111035330 55111035360 66544000201 66828001301 000078032506 NDC for "rivastigmine 4.5 MG Oral Capsule": 000078032508 000078032544 00078032506 00078032508 00078032515 00078032544 00615136931 00615136939 055111-*354-01 055111-*354-05 055111-*354-30 055111-*354-60 17088002001 54868524000 55111035401 55111035405 55111035430 55111035460 66828001401 000078032506 NDC for "rivastigmine 4.5 MG Oral Capsule": 000078032508 000078032544 00078032506 00078032508 00078032515 00078032544 00615136931 00615136939 055111-*354-01 055111-*354-05 055111-*354-30 055111-*354-60 17088002001 54868524000 55111035401 55111035405 55111035430 55111035460 66828001401 000078032506 NDC for "rivastigmine 4.5 MG Oral Capsule": 000078032508 000078032544 00078032506 00078032508 00078032515 00078032544 00615136931 00615136939 055111-*354-01 055111-*354-05 055111-*354-30 055111-*354-60 17088002001 54868524000 55111035401 55111035405 55111035430 55111035460 66828001401 000456321021 NDC for "Memantine 10 MG Oral Tablet": 000456321022 000456321060 000456321063 00247212130 00247212160 00456321010 00456321011 00456321021 00456321022 00456321060 00456321063 00615650805 00615650831 00615650839 12280028430 12280028460 21695016930 21695016960 26053021501 49999080430 49999080460 51129284901 51129284902 55154461508 55154461800 55289093730 55289093760 58864088730 63711041010 67544050531 67544050532 63711041510 NDC for "Memantine 15 MG Oral Tablet": 000456320212 NDC for "Memantine 2 MG/ML Oral Solution": 00456320212 63711042010 NDC for "Memantine 20 MG Oral Tablet": 000456320521 NDC for "Memantine 5 MG Oral Tablet": 000456320522 000456320560 000456320563 00456320511 00456320521 00456320522 00456320560 00456320563 00615651931 00615651939 12280038160 21695023260 26053021601 54868565400 55154461700 63629338301 63629338302 63629338303 63629338304 63711040510 67544062631 run; %GetRxForDrugs( NdcCodest /* The name of a dataset containing the NDCs of the drugs whose fills you want. */ , &StartDt /* The date on which you want to start collecting fills.*/ , &EndDt /* The date on which you want to stop collecting fills. */ , AlzRxPeople /* The name of the output dataset containing the fills. */ ) ;