this study was approved by the local ethics committee , and each patient gave informed consent for participation . the clinical diagnosis of pd was made according to the uk brain bank criteria.11 at the time of the study , none of the patients had ever taken medications for pd . all patients underwent a detailed clinical evaluation , including laboratory tests for lipid profiles and serum homocysteine . at the time of study enrollment , all included patients were evaluated using the unified parkinson s disease rating scale ( updrs ) and the modified hoehn and yahr staging score . patients fasted the night before the test , except for a small amount of water , if they were thirsty and abstained from drinking alcohol or coffee the day before the study . continuous electrocardiographic and non - invasive blood pressure monitoring was used in each patient ( ym6000 , mediana tech . , san antonio , tx , usa ) . after 30 min of supine rest , the test ( 20 min at 60 ) was performed using the manumed special tilt1-section ( enraf nonius , rotterdam , the netherlands ) . by consensus , orthostatic hypotension was defined as a fall in blood pressure of at least 20 mm hg systolic pressure and/or 10 mm hg diastolic pressure between 2 and 5 minutes after tilt.12 all patients enrolled in the study underwent conventional mri with a 3.0-t system ( magnetom verio , 3 t , siemens ) . axial t2 weighted images , complemented with coronal fluid attenuated recovery images , were used to rate the wmh . the mr images were rated using the semiquantitative visual rating system of scheltens et al.13 this rating scale provides four sum scores in a semiquantitative way ; periventricular hyperintensities ( 06 ) , deep wmh ( 024 ) , basal ganglia hyperintensities ( 030 ) , and infratentorial hyperintensities ( 030 ) . periventricular hyperintensities were identified as continuous , confluent areas of high signal intensity adjacent to the anterior or posterior horns of the lateral ventricles (  cap  ) and along the lateral ventricles (  bands  ) . absence of lesions was a score of 0 ,  5 mm lesions was a score of 1 , and a score of 2 was given for lesions > 5 mm . wmh , located in the deep and subcortical white matter , were separately rated in the frontal , temporal , parietal , and occipital regions according to the previously described criteria.13 these rating criteria were also applied to regions of the basal ganglia ( caudate , putamen , globus pallidus , thalamus , and internal capsule ) and infratentorial regions ( cerebellum , midbrain , pons , and medulla ) . the independent sample t - test or pearson s chi - square test was used to compare the differences between the groups categorized by the blood pressure response during orthostasis ( non - oh and oh ) . given the potential influence of several variables on the results of wmh , we also conducted group comparisons with an analysis of covariance ( ancova ) including age , the presence of hypertension and diabetes , low density lipoprotein ( ldl)-cholesterol , and serum homocysteine levels as confounding covariates . patients were also divided into no to mild and severe wmhs groups based on two extremes by tertile distribution . the relationship between blood pressure profiles monitored during tilt table testing tilt and wmh were tested using spearman s rank correlation coefficients . the statistical analysis was performed with spss software version 15.0 ( spss , inc . , this study was approved by the local ethics committee , and each patient gave informed consent for participation . the clinical diagnosis of pd was made according to the uk brain bank criteria.11 at the time of the study , none of the patients had ever taken medications for pd . all patients underwent a detailed clinical evaluation , including laboratory tests for lipid profiles and serum homocysteine . at the time of study enrollment , all included patients were evaluated using the unified parkinson s disease rating scale ( updrs ) and the modified hoehn and yahr staging score . patients fasted the night before the test , except for a small amount of water , if they were thirsty and abstained from drinking alcohol or coffee the day before the study . continuous electrocardiographic and non - invasive blood pressure monitoring was used in each patient ( ym6000 , mediana tech . , san antonio , tx , usa ) . after 30 min of supine rest , the test ( 20 min at 60 ) was performed using the manumed special tilt1-section ( enraf nonius , rotterdam , the netherlands ) . by consensus , orthostatic hypotension was defined as a fall in blood pressure of at least 20 mm hg systolic pressure and/or 10 mm hg diastolic pressure between 2 and 5 minutes after tilt.12 all patients enrolled in the study underwent conventional mri with a 3.0-t system ( magnetom verio , 3 t , siemens ) . axial t2 weighted images , complemented with coronal fluid attenuated recovery images , were used to rate the wmh . the mr images were rated using the semiquantitative visual rating system of scheltens et al.13 this rating scale provides four sum scores in a semiquantitative way ; periventricular hyperintensities ( 06 ) , deep wmh ( 024 ) , basal ganglia hyperintensities ( 030 ) , and infratentorial hyperintensities ( 030 ) . periventricular hyperintensities were identified as continuous , confluent areas of high signal intensity adjacent to the anterior or posterior horns of the lateral ventricles (  cap  ) and along the lateral ventricles (  bands  ) . absence of lesions was a score of 0 ,  5 mm lesions was a score of 1 , and a score of 2 was given for lesions > 5 mm . wmh , located in the deep and subcortical white matter , were separately rated in the frontal , temporal , parietal , and occipital regions according to the previously described criteria.13 these rating criteria were also applied to regions of the basal ganglia ( caudate , putamen , globus pallidus , thalamus , and internal capsule ) and infratentorial regions ( cerebellum , midbrain , pons , and medulla ) . the independent sample t - test or pearson s chi - square test was used to compare the differences between the groups categorized by the blood pressure response during orthostasis ( non - oh and oh ) . given the potential influence of several variables on the results of wmh , we also conducted group comparisons with an analysis of covariance ( ancova ) including age , the presence of hypertension and diabetes , low density lipoprotein ( ldl)-cholesterol , and serum homocysteine levels as confounding covariates . patients were also divided into no to mild and severe wmhs groups based on two extremes by tertile distribution . the relationship between blood pressure profiles monitored during tilt table testing tilt and wmh were tested using spearman s rank correlation coefficients . the statistical analysis was performed with spss software version 15.0 ( spss , inc . , among the 117 patients enrolled , 46 were men and 71 were women . the mean age at examination was 68.5  10.1 years , and the mean duration of motor symptoms was 2.1  1.0 years . the severities of parkinsonian motor symptoms were as follows : mean total updrs score was 24.7  17.9 ( part 1 , 2.2  2.3 ; part 2 , 7.2  5.8 ; part 3 , 14.8  10.7 ) . twenty - nine patients had hypertension ( hbp ) , 24 had diabetes mellitus ( dm ) , and 106 were non - smokers . the presence or absence of hypertension and diabetes , and current / past smoking habits did not affect cerebral wmh ( hbp vs. no hbp group : 14.9  8.6 vs. 11.9  9.0 , f = 1.295 , p = 0.258 ; dm vs. no dm group : 15.8  6.7 vs. 11.8  9.3 , f = 2.118 , p = 0.148 ; non - smoker vs. ex - smoker vs. current - smoker 12.9  8.9 vs. 9.8  10.1 vs. 11.7  8.4 , f = 0.259 , p = 0.772 , by ancova controlling for age , ldl - cholesterol and serum homocysteine ) . higher ldl - cholesterol and serum homocysteine levels also did not correspond to increasing wmh scores ( r = 0.004 , p = 0.965 in ldl - cholesterol ; r = 0.071 , p = 0.494 in homocysteine by spearman s rank correlation ) . clinical and laboratory profiles of the groups with and without orthostatic hypotension are presented in table 1 . data from patients with and without orthostatic hypotension were similar for age , gender , duration of illness , severity of parkinsonian motor symptoms , and proportion of patients with hypertension and diabetes . among the 42 patients with oh , 29 were clinically symptomatic ( 69.1% ) . the wmh scores were higher in the orthostatic hypotension group compared to those in the non - oh group after controlling for age , the presence of hypertension and diabetes , ldl - cholesterol and serum homocysteine . in addition , a trend of more wmh lesions in the supratentorial region of the oh group was also found ( table 2 ) . on correlation analysis , orthostatic diastolic blood pressure change was positively correlated with white matter changes ( figure 1a and b ) . on the other hand , supine blood pressures were closely correlated with the wmh scores of the whole brain ( figure 1c and d ) . when comparing groups with extremes of wmhs , the severe wmh group had higher supine systolic bp and larger fall in bp during orthostasis ( figure 2 ) . epidemiological investigations in healthy populations have shown that wmh predict the risk of cerebrovascular disease , cognitive dysfunction , and mortality.1 advanced age , arterial hypertension , diabetes , and elevated serum homocysteine levels are risk factors for increasing wmh.24,14,15 however , these associations remain unclear in patients with pd.5,6 in this study , the presence or absence of cerebrovascular risk factors was not associated with wmh in patients with pd . this finding is consistent with previous studies and suggests that other nonvascular factors contribute to the vascular brain damage in patients with pd . orthostatic hypotension is common in patients with pd and appears more frequently as disease progresses and influence subjective symptoms , quality of life , and disease treatment.16 recent investigations in patients with multiple system atrophy indicate that supine systolic blood pressure and/or blood pressure changes during orthostasis are significantly and independently correlated with wmh.17,18 however , a similar phenomenon was not confirmed in patients with pd.18 prior studies were not performed in patients with early stage and the enrolled patients were not free from drug effects . in this study , we enrolled only newly diagnosed patients with early stage pd who had not taken any dopaminergic medication . because dopaminergic drugs can aggravate orthostatic hypotension , this result suggests that this association was independent from anti - parkinsonian treatment . we found that the orthostatic hypotension group had more severe wmh changes and that the differences in wmh were more significant in the deep white matter region . although the hemodynamic consequences during orthostasis have not been clarified , it was reported that systemic blood flow is inversely associated with wmhs in the elderly.19 because orthostatic hypotension leads to recurrent blood pressure drops , this could result in cerebral hypoperfusion and impact neurocirculatory failures , perhaps via cerebral small - vessel disease.20 supine blood pressures can also contribute myriad episodes of cerebral hypo- and hyper - perfusion to white matter injuries . in addition to neurocirculatory insufficiency , degenerative processes associated with aging and disease itself may contribute to the generation of wmh in pd . in summary , our results indicate that hemodynamic changes associated with orthostatic hypotension may be associated with white matter changes in patients with pd .