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1 Supplementary Online Content Nead KT, Gaskin G, Chester C, Swisher-McClure S, Leeper NJ, Shah NH. Association between androgen deprivation therapy and risk of dementia. JAMA Oncol. Published online October 13, doi: /jamaoncol etable 1. Concepts and Terms Defining Prostate Cancer and Alzheimer Disease in Clinical Text Analysis etable 2. Variable ICD-9 Diagnostic Codes etable 3. Gleason Score Distribution in Available Patients (n=4360) etable 4. Traditional Multivariable Cox Proportional Hazards Regression for the Association of Androgen Deprivation Therapy With Negative Controls eappendix. Medication Names Queried to Identify Individuals on Androgen Deprivation Therapy efigure. Kaplan-Meier Curves Examining the Age-Stratified Cumulative Probability of Remaining Dementia Free in the Unmatched Cohort

2 etable 1. Concepts and Terms Defining Prostate Cancer and Alzheimer Disease in Clinical Text Analysis String Drug/Event Concept Unique Identifier dementia Dementia C alzheimer's disease Dementia C alzheimer disease Dementia C alzheimer's dementia Dementia C vascular dementia Dementia C frontotermporal dementia Dementia C senile dementia Dementia C alzheimer dementia Dementia C multi-infarct dementia Dementia C disease, alzheimer Dementia C dementias Dementia C multiinfarct dementia Dementia C disease, alzheimer's Dementia C dementia nos Dementia C pick disease Dementia C vascular dementia, uncomplicated Dementia C semantic dementia Dementia C dementia in alzheimer's disease Dementia C multi infarct dementia Dementia C pick's disease Dementia C alzheimer type dementia Dementia C senile dementia uncomp Dementia C early onset alzheimer disease Dementia C dementia, vascular Dementia C dementia, nos Dementia C dementia, alzheimer type Dementia C dementia, unspecified Dementia C unspecified dementia Dementia C presenile dementia Dementia C senile dementia with delirium Dementia C binswanger's disease Dementia C frontotemporal dementias Dementia C dementia, multiinfarct Dementia C dementia alzheimer's type Dementia C vascular dementia with delirium Dementia C dementia in conditions classified elsewhere Dementia C senile dementia, uncomplicated Dementia C frontotemporal lobe dementia Dementia C

3 String Drug/Event Concept Unique Identifier dementia, senile Dementia C dementia, multi-infarct Dementia C subcortical leukoencephalopathy Dementia C dementia vascular Dementia C late onset alzheimer disease Dementia C picks disease Dementia C alzheimer's disease with early onset Dementia C senile dementia, alzheimer type Dementia C dementia in alzheimer's disease with early onset Dementia C binswanger's dementia Dementia C subcortical vascular dementia Dementia C dementia, semantic Dementia C senile dementia with paranoia Dementia C senile delusion Dementia C binswanger disease Dementia C alzheimer disease, late onset Dementia C pre-senile dementia Dementia C alzheimers dis Dementia C multi-infarct, dementia Dementia C vascular dementias Dementia C disease, pick Dementia C vascular dementia with depressed mood Dementia C dementia, frontotemporal Dementia C multi-infarct dementias Dementia C alzheimer disease, early onset Dementia C chronic progressive subcortical encephalopathy Dementia C dementia, multi infarct Dementia C disease, pick's Dementia C multi-infarct dementia with delirium Dementia C dementia in conditions ec Dementia C dementia, presenile Dementia C dementia in alzheimer's disease with late onset Dementia C dementia due to pick's disease Dementia C dementia multi-infarct Dementia C senile dementia nos Dementia C alzheimer's disease with late onset Dementia C adenocarcinoma of prostate Prostate Cancer C adenocarcinoma of the prostate Prostate Cancer C ca - cancer of prostate Prostate Cancer C ca prostate Prostate Cancer C

4 cancer of prostate Prostate Cancer C String Drug/Event Concept Unique Identifier cancer of the prostate Prostate Cancer C cancer, prostate Prostate Cancer C cancer, prostatic Prostate Cancer C cancers, prostate Prostate Cancer C carcinoma of prostate Prostate Cancer C carcinoma of the prostate Prostate Cancer C carcinoma prostate Prostate Cancer C carcinoma prostatic Prostate Cancer C ductal adenocarcinoma of the prostate Prostate Cancer C embryonal rhabdomyosarcoma of the prostate Prostate Cancer C endometrioid carcinoma of the prostate Prostate Cancer C hormone refractory prostate cancer Prostate Cancer C hormone-refractory prostate cancer Prostate Cancer C leiomyosarcoma of prostate Prostate Cancer C leiomyosarcoma of the prostate Prostate Cancer C malignant neoplasm of prostate Prostate Cancer C malignant neoplasm of the prostate Prostate Cancer C metastatic prostate cancer Prostate Cancer C metastatic prostate carcinoma Prostate Cancer C neuroendocrine tumor of the prostate Prostate Cancer C pn0 prostate cancer Prostate Cancer C pn1 prostate cancer Prostate Cancer C prostate adenocarcinoma Prostate Cancer C prostate cancer Prostate Cancer C prostate cancer metastatic Prostate Cancer C prostate cancer recurrent Prostate Cancer C prostate cancer stage i Prostate Cancer C prostate cancer stage ii Prostate Cancer C prostate cancer stage iv Prostate Cancer C prostate cancers Prostate Cancer C prostate carcinoma Prostate Cancer C prostate carcinoma metastatic Prostate Cancer C prostate ductal adenocarcinoma Prostate Cancer C prostate embryonal rhabdomyosarcoma Prostate Cancer C prostate rhabdomyosarcoma Prostate Cancer C prostate sarcoma Prostate Cancer C prostatic cancer Prostate Cancer C prostatic cancer metastatic Prostate Cancer C prostatic cancers Prostate Cancer C

5 prostatic carcinoma Prostate Cancer C pt2 prostate cancer Prostate Cancer C String Drug/Event Concept Unique Identifier pt2a prostate cancer Prostate Cancer C pt2b prostate cancer Prostate Cancer C pt2c carcinoma of prostate Prostate Cancer C pt2c prostate cancer Prostate Cancer C pt3 prostate cancer Prostate Cancer C pt3b prostate cancer Prostate Cancer C recurrent cancer of the prostate Prostate Cancer C recurrent prostate cancer Prostate Cancer C recurrent prostate carcinoma Prostate Cancer C rhabdomyosarcoma of prostate Prostate Cancer C rhabdomyosarcoma of the prostate Prostate Cancer C sarcoma of prostate Prostate Cancer C sarcoma of the prostate Prostate Cancer C small cell carcinoma of the prostate Prostate Cancer C stage i prostate cancer Prostate Cancer C stage ii prostate cancer Prostate Cancer C stage iii prostate cancer Prostate Cancer C stage iv prostate cancer Prostate Cancer C

6 etable 2. Variable ICD-9 diagnostic Codes Term ICD-9 code(s) CPT code(s) Prostate cancer 185 Radical prostatectomy , Dementia , or Cardiovascular disease 443.9, 440.2, 428, 413, 414 (excluding 414.1x), 412, 411, 410; 410 and 412 if prior to prostate cancer diagnosis Diabetes 250; 357.2; X; Stroke 430, 431, 432, 433, 434, 436 Malignancy ; 174; 175; ;

7 etable 3. Gleason Score Distribution in Available Patients (n=4360) Gleason score n % % % % 6 2, % 7 1, % % % %

8 etable 4. Traditional Multivariable Cox Proportional Hazards Regression for the Association of Androgen Deprivation Therapy with Negative Controls Outcome HR (95% CI) P Value n* Tuberculosis 1.55 ( ) Allergic rhinitis 1.32 ( ) Abdominal aortic aneurysm 1.00 ( ) HR, Hazard ratio; CI, confidence interval Adjusted for age, race, smoking status, anti-coagulant, anti-platelet, anti-hypertensive and statin therapy, and history of cardiovascular disease, diabetes, stroke or malignancy *Number of relevant failure events

9 eappendix. Medication Names Queried to Identify Individuals on Androgen Deprivation Therapy Leuprolide, goserelin, triptorelin, histrelin, Degarelix, flutamide, bicalutamide, nilutamide, Enzalutamide, Cyproterone acetate, Lupron, Zoladex, Trelstar, Vantas, Firmagon, Eulexin, Casodex, Nilandron, Xtandi, Nizoral, Androcur, Eligard, Cyprostat, Anandron, Flutamin, Cytomid, Cosudex, Calutide, Kalumid

10 efigure. Kaplan-Meier Curves Examining the Age-Stratified Cumulative Probability of Remaining Dementia Free in the Unmatched Cohort Non-ADT users < 70 years, n=4,844; ADT users < 70 years, n=925; Non-ADT users 70 years, n=2,602; ADT users 70 years, n=901. Each curve was independently statistically significantly different from all other curves (P < 0.05) ADT, Androgen deprivation therapy.

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