Mitsuru Shinohara1,2,3, Yoshitaka Tashiro1, Kaoru Suzuki1, Akio Fukumori1,2, Guojun Bu3, Naoyuki Sato1,2. 1. Department of Aging Neurobiology Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology Obu Aichi Japan. 2. Department of Aging Neurobiology Graduate School of Medicine Osaka University Suita Osaka Japan. 3. Department of Neuroscience Mayo Clinic Jacksonville Florida USA.
Abstract
INTRODUCTION: Although diabetes and apolipoprotein E (apoE) are both significant risk factors for dementia, including Alzheimer's disease, it remains to be clarified how they are related to each other in contributing to the risk of dementia. METHODS: By reviewing the National Alzheimer's Coordinating Center (NACC) clinical records, we investigated whether diabetes affects cognitive decline depending on APOE genotype and their potential relationships with neuropathology. RESULTS: A significant interaction between diabetes and APOE genotype exists, where diabetes affected cognitive decline in APOE3 carriers and APOE2 carriers, but not APOE4 carriers. Moreover, the presence of vascular pathology was increased by diabetes in APOE3 carriers, while APOE4 carriers nearly reached plateau levels irrespective of diabetes. DISCUSSION: Diabetes accelerates cognitive decline, in part, through accelerating vascular impairment in non-APOE ε4 carriers, but such effects are negligible in APOE4 carriers, who themselves are already vulnerable to vascular impairment.
INTRODUCTION: Although diabetes and apolipoprotein E (apoE) are both significant risk factors for dementia, including Alzheimer's disease, it remains to be clarified how they are related to each other in contributing to the risk of dementia. METHODS: By reviewing the National Alzheimer's Coordinating Center (NACC) clinical records, we investigated whether diabetes affects cognitive decline depending on APOE genotype and their potential relationships with neuropathology. RESULTS: A significant interaction between diabetes and APOE genotype exists, where diabetes affected cognitive decline in APOE3 carriers and APOE2 carriers, but not APOE4 carriers. Moreover, the presence of vascular pathology was increased by diabetes in APOE3 carriers, while APOE4 carriers nearly reached plateau levels irrespective of diabetes. DISCUSSION: Diabetes accelerates cognitive decline, in part, through accelerating vascular impairment in non-APOE ε4 carriers, but such effects are negligible in APOE4 carriers, who themselves are already vulnerable to vascular impairment.
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