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Supplementary Table 1 | Summary of the main anti-inflammatory clinical trials in Alzheimer disease and amyotrophic lateral sclerosis Study Trial Location Age Patient Drug Duration Results type (years) sample Alzheimer disease McGeer et al., P USA UR Rheumatoid NSAIDs lifetime Protection 19901 arthritis patients May et al., P USA >80 Ambulatory NSAIDs 3 years No protection 19922 elderly population Rogers et al., T USA UR AD Indomethacin 6 months Protection 19933 participants Breitner et al., P USA UR Twin pairs NSAIDs >1 year Protection 19944 CSHA, 19945 P Canada >65 Community/ NSAIDs NR Protection institution residents Saag et al., P USA >65 Community/ NSAIDs 2 weeks No protection; risk factor for 19956 institution longitudinal memory decline Residents (EPESE) Andersen et P Netherla >55 Community/ NSAIDs current use Protection al., 19957 nds institution Residents Breitner et al., P USA >65 Family of AD NSAIDs >1 year Protection 19958 patients Rozzini et al., P Italy >65 Community/ NSAIDs 3 years Protection 19969 institution residents (EPESE) Fourrier et P France >65 Community/ NSAIDs 1–3 years No protection al., 199610 institution Residents Hanlon et al., P USA >65 Community/ NSAIDs NR No protection 199711 institution residents (EPESE) Stewart et al. , P USA <65 Community/ NSAIDs >2 years Protection 199712 institution residents Henderson et P Australia >70 Community/ NSAIDs 3–4 years No protection al., 199713 institution residents Beard et al., P USA >65 patients at NSAIDs >7 days Protection 199814 Mayo Clinic within 2 years Prince et al., P USA >70 Participates of NSAIDs 4.5 years Protection; 199815 hypertension No protection in people older than trail 74 years Scharf et al., T USA UR AD Diclofenac or 6 months No deceleration 199916 participants misoprostol Broe et al., P Australia >75 Community NSAIDs current use Protection only at low dose 200017 survey Ganguli et al., P USA >65 Community NSAIDs >2 years No protection 200018 survey in t’ Veld et P Netherla >55 Community/ NSAIDs >2 years Protection only at low dose al., 200119 nds institution residents Lindsay et al., P Canada >65 Community/ NSAIDs lifetime Protection 200220 institution residents Wolfson et al., P Canada >65 Community/ NSAIDs 3 years Protection 200221 institution residents (CSHA) Zandi et al., P USA >65 Community/ NSAIDs >2 years Protection 200222 institution residents Nilsson et al., P Sweden >80 Twin pairs of NSAIDs 3 years No protection 200323 same sex Jonker et al., T Netherla 62-85 Community/ NSAIDs 1 year No deceleration 200324 nds institution residents (LASA) Landi et al., P Italy UR Community/ NSAIDs within 2 Protection 200325 institution weeks residents preceding (arthritis assessment diagnosed) Hee Kang et P USA 70-81 Community/ Ibuprofen >2 years Protection al., 200326 institution residents (Nurses’ health study) Aisen et al., T USA UR AD Rofecoxib or 1 year No deceleration 200327 participants naproxen Reines et al., T USA >50 AD Rofecoxib 1 year No deceleration 200428 participants Thal et al., T USA >65 AD Rofecoxib 4 years No deceleration 200529 participants Yip et al., P USA >50 Community/ NSAIDs >6 months Protection 200530 institution residents Vlad et al., P USA >55 Community/ Ibuprofen 1-5 years Protection 200831 institution residents Martin et al., P USA >70 ADAPT Celecoxib 3 years No protection 200832 Naproxen sodium Arvanitakis et P USA >75 Religious NSAIDs >2 years No protection al., 200833 Orders Study Breitner et al., P USA >65 Community/ NSAIDs >2 years Heavy use increased risk of 200934 institution dementia (66%) residents (ACT study)

Amytrophic lateral sclerosis Cudkowicz et T USA 40-67 ALS Celecoxib 1 year No protection al., 200635 participants Meininger et T Europe 18-80 ALS Pentoxifylline 18 months Increased risk of death (43%) al., 200636 participants Gordon et al., T USA 21-85 ALS Minocycline 9 months Harmful effect 200737 participants Abbreviations: ACT, Adult Changes in Thought; AD, Alzheimer disease; ADAPT, Alzheimer Disease Anti-inflammatory Prevention Trial; CSHA, ALS, amyotrophic lateral sclerosis; Canadian Study of Health and Aging; EPESE, Established Populations for Epidemiologic Studies of the Elderly; LASA, Longitudinal Aging Study Amsterdam; NR, not reported; P, preventative; T, therapeutic; UR, unrestricted.

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