Objective To explore the levels of serum alkaline phosphatase ( ALP) as well as its impact on the cognitive impairment in patients with subcortical ischemic vascular disease ( SIVD).Methods One hundred and fifty-eight SIVD patients were divided into two subgroups which included 86 patients with mild cognitive impairment ( SVMCI ) and 72 patients with vascular dementia ( SVaD ) according to the severity of cognitive impairment.Sixty-seven old people with normal cognitive function were selected as control qruop.Multiple lacunar infarction ( LI) or leukoaraiosis ( LA) was detected according to their MRI scan appearances and graded LA according to the severity.Serum ALP was measured by an enzymatic method as well as the Mini-Mental State Examination ( MMSE) and the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C) were used in assessments.Serum ALP was divided into 3 groups and the occurrence rate of LI , LA and cognitive impairment were compared with each other.The levels of ALP were compared in different cognitive impairment and Logistic regression was used to explore the relation between ALP and cognitive impairment.Results Both SVaD and SVMCI groups (17.00 (13.00, 20.00), 59.50 (49.00, 68.75);25.00 (25.00, 26.00), 82.50 (76.75, 89.00)) showed significantly lower scores in MMSE and CAMCOG-C than control group (28.00 (28.00, 29.00), 93.00 (89.00, 96.00); Z=187.337, P=0.000; Z=150.480, P=0.000).A positive relationship between the elevated ALP level and the severity of cognitive impairment was found after adjusting for sex , age and other confunding factors ((68.60 ±15.52), (78.76 ±13.39), (86.75 ±18.85) U/L, F=22.587, P=0.000).The occurrence rate of LI, LA and SVaD among the three groups were significantly different (χ2 =8.008, P=0.018;χ2 =17.998, P=0.000;χ2 =12.255, P=0.002).The ALP level was negatively correlated with MMSE and CAMCOG-C scores ( r=-0.350, P=0.000; r=-0.286, P=0.000 ).Logistic regression analysis revealed the relation between ALP and cognitive impairment was positive when we controlled all the vascular risk factors.However , the relation had gone when futher adjusting for the grade of LA.Conclusions The level of ALP is significantly higher in SIVD patients and positively relates with cognitive impairment especially in those whose grade of LA is severe.