Sex Difference in Effects of Low-Dose Aspirin on Prevention of Dementia in Patients With Type 2 Diabetes: A Long-term Follow-up Study of a Randomized Clinical Trial
Authors: Matsumoto Chisa , Ogawa Hisao , Saito Yoshihiko , Okada Sadanori , Soejima Hirofumi , Sakuma Mio , Masuda Izuru , Nakayama Masafumi , Doi Naofumi , Jinnouchi Hideaki , Waki Masako , Morimoto Takeshi ,   JPAD Trial Investigators, Miwa Kimiaki , Akahoshi Kazunobu , Misumi Kenji , Araki Haruo , Mitsudo Yutaka , Kondo Norifumi , Ashihara Kenichi , Yumoto Shinya , Horimoto Masashi , Doi Osamu , Doijiri Kenichi , Fukami Ryo , Shimabukuro Michio , Egusa Genshi , Goto Kazuo , Hanaoka Yoichi , Kimura Yoshihiro , Haraguchi Yoshikuni , Haraguchi Osamu , Hasegawa Atsushi , Shioya Yoshiko , Shioya Yosuke , Tanaka Eiitiro , Yamada Kazuhiko , Atsumi Toshiya , Tanazawa Satoshi , Horio Yutaka , Ichihara Seishi , Yasuda Isao , Ikeda Tsuneo , Ikemura Makoto , Imamoto Chieko , Iseri Yoshihisa , Iwai Ken , Okamoto Shinya , Sugiyama Seigo , Kamura Masanori , Kan Hirofumi , Kiyota Mayumi , Kawamura Kyousuke , Ono Takashi , Koga Takeshi , Kinuwaki Etsuo , Naito Hiromichi , Kozuma Kazuo , Kudou Kiyotaka , Morikami Yasuhiro , Yasue Hirofumi , Mizuno Yuji , Fujimoto Hisao , Matsuyama Kozaburo , Fujii Hiromi , Kamijikkoku Syuichi , Kuwahara Tetsuo , Takaoka Kyoji , Machii Kazuo , Maeda Kazutaka , Mahara Keiji , Maki Akira , Manda Naoki , Marutsuka Kousuke , Sameshima Naoki , Gi Toshihiro , Matsunaga Terufumi , Matsuo Syuichi , Okubo Hiroto , Minagawa Fuyuki , Minoda Kotaro , Miyata Junichi , Matsuo Takeshi , Momosaki Sueo , Munakata Tetsuo , Nakamura Tomoki , Nagano Hisatoshi , Goshi Kazuto , Sugimoto Keisuke , Naomi Shojiro , Nasu Toshiaki , Tanaka Hiroyuki , Sonoda Ryuji , Kajiwara Keizo , Odo Takafumi , Ogata Hirofumi , Ogihara Masayuki , Ogura Tateo , Oka Keishiro , Kawashima Eiji , Oshima Eiji , Ozaki Ken , Ozawa Seiji , Shono Hiroyuki , Sakamoto Yasuhiro , Sakurai Nobuko , Wakabayashi Chikashi , Sawada Tomohiro , Shibata Junji , Shimono Hisashi , Iemura Akihiro , Matsutani Akira , Suefuji Hisakazu , Sugiyama Hiromichi , Hokamaki Jun , Komori Kenichi , Kinoshita Yoshimi , Murakami Hironori , Hashiguchi Jun , Hashiguchi Yasuhiro , Sawai Koryo , Hifumi Atuko , Seo Koji , Toihata Masamitsu , Tokube Koji , Ogawa Hiroshi , Tomita Fumishi , Taguchi Madoka , Tsubokura Toshio , Tsuchiya Tatsuaki , Tsuda Kaoru , Tsurusaki Ryuichiro , Obata Kenji , Watanabe Katumi , Hayasida Raisuke , Ishibashi Yutaka , Osamura Yoshiaki , Yamanaka Yoshito , Sonoda Kazuhiro , Iwaoka Taisuke , Yokota Hiromitsu , Yoshinari Motoki , Abe Nanami , Ando Noriaki , Bando Hiroshi , Takami Takeshi , Doi Michiaki , Fujii Yoshihiro , Fukuda Masahiro , Fukuoka Yoshiaki , Hamano Masayoshi , Takaoka Minoru , Hasegawa Hiromi , Yabuta Ikuo , Higami Kenshi , Higami Satomi , Yasuno Akiko , Fujinaga Yuriko , Onishi Yoko , Yoshimura Katsutoshi , Minami Shigetoshi , Nakashima Takao , Horie Hiroaki , Horii Kazuko , Matsumura Norihiko , Ikuno Tetsuo , Katsuyama Yoshiyuki , Uemura Shiro , Kikukawa Masao , Kanauchi Masao , Kuzuya Hideshi , Iwasaki Arata , Koutani Takehiko , Makino Hisaharu , Miki Hiroshi , Misugi Susumu , Naito Masaki , Naito Masatoshi , Nakano Yukitaka , Nakatani Akira , Nakatani Fumihiko , Horii Manabu , Yabuta Matahiro , Seno Ayako , Kawata Hiroyuki , Samejima Kenichi , Onoue Kenji , Kawakami Rika , Nakano Tomoya , Ueda Tomoya , Soeda Tsunenari , Kita Yoko , Inoue Fumitaka , Yamano Shigeru , Iwama Hajime , Sakan Hirokazu , Suzuki Megumi , Kagoshima Tadashi , Nakai Takehito , Hashimoto Toshio , Nishitani Yoshiharu , Kobayashi Yoshiyuki , Hoda Koichi , Fujiki Kengo , Uejima Junko , Morikawa Yoshinobu , Kawano Takahiro , Yamada Hideki , Nishimoto Kazuo , Ohsumi Kyouyuki , Ote Nobushige , Oya Akiko , Nishiura Kimiaki , Masuda Joji , Ban Keiichiro , Kyoda Yusuke , Sawada Izumi , Sawada Yoko , Okada Koichi , Yazaki Akihiro , Hanatani Masakazu , Sutani Toshio , Hiramori Yuko , Tanaka Yuya , Igaki Toshiro , Tomioka Yukio , Shiiki Hideo , Sugihara Kiyotaka , Hayashi Motomu , Sasaki Yasunobu , Matsukura Yasuo , Ueda Michiaki , Ueyama Masakuni , Uyama Hideto , Yamada Hiroharu , Yamaga Kenichi , Nakajima Tamio , Yoshimoto Kazumi , Yoshimura Midori 
Published: December 2019

OBJECTIVE
To evaluate and compare the efficacy of long-term use of low-dose aspirin for the prevention of dementia in men and women.

RESEARCH DESIGN AND METHODS
This study is a follow-up cohort study of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial, which was a randomized, open-label, standard care–controlled trial examining the effects of low-dose aspirin on cardiovascular events. We followed up 2,536 Japanese patients with type 2 diabetes (T2D) enrolled in the JPAD trial from 2002 to 2017. The primary outcome of this post hoc analysis was the incidence of dementia, which was defined by the prescription of antidementia drugs or admission due to dementia.

RESULTS
Among the originally enrolled patients, 2,121 (84%) retained their original allocation. During a median follow-up of 11.4 years, 128 patients developed dementia. The overall effect of low-dose aspirin on the prevention of dementia adjusted for age, sex, and other established risk factors was not significant (hazard ratio [HR] 0.82, 95% CI 0.58–1.16). However, a significant reduction was seen in the risk of dementia in women (HR 0.58, 95% CI 0.36–0.95), but not in men (HR 1.27, 95% CI 0.75–2.13) (Pinteraction = 0.03).

CONCLUSIONS
Long-term use of low-dose aspirin may reduce the risk for dementia in women with T2D.