MAPT and Alzheimer disease: Many studies found that smoking was significantly associated with an increased risk of dementia [16, 44–46], which is reinforced by the following plausible biological mechanisms: (1) smoking is a well-known risk factor for stroke [47], and thus may cause vascular dementia and AD [48]; and (2) smoking would adversely affect neurodegeneration through oxidative stress and inflammation [49] that were associated with increased production of amyloid-β and abnormal tau protein phosphorylation which are hypothesized to cause AD [50].