Associations Of White Matter Hyperintensities With Cognition,neuropsychiatric Symptoms,and Daily Activities In Alzheimer's Disease

Background:There was a higher prevalence of white matter hyperintensities in patients of Alzheimer's disease(AD)than in the normal elderly.White matter hyperintensities can be categorized into periventricular white matter hyperintensities(PWMH)and deep white matter hyperintensities(DWMH).The previous studies on the relation of cognitive and white matter hyperintensities mostly focused on the overall white matter hyperintensities.However,further to analyses regarding the association of PWMH and DWMH with cognitive function is less.Furthermore,few investigations have been done on the relationship between white matter hyperintensities and neuropsychiatric symptoms,as well as the ability of activities of daily living(ADL)in patients with AD.At the same time,the results of these studies are partly controversial.In dementia research,the focus is largely on the amyloid hypothesis,and the influence of cerebral small vessel disease,including WMH,is sometimes neglected.However,in order to delay the onset and development of AD,the effects of vascular factors,including WMH,should also be knowed and addressed.Objectives:This study used The Clinical Research Center for Dementia of South Korea(CREDOS)rating scales categorized WMH as DWMH and PWMH,that it aimed at exploring respectively the relationship between DWMH or PWMH and cognitive function,ADL,and neuropsychiatric symptoms in patients with Alzheimer's disease(AD).Methods:The clinical research recruited 88 patients with AD in the inpatient and outpatient settings of Guangzhou Huiai Hospital(Guangzhou Brain Hospital)from December 2012 to March 2016.All patients underwent Mini-Mental State Examination(MMSE)and Clinical Dementia Rating(CDR)to determine the severity of dementia.Frequency of occurrence and severity of BPSD were evaluated using the Neuropsychiatry Inventory(NPI).Cornell scale for depression in dementia(CSDD)and Cohen-Mansfield(CMAI)were used to evaluate the symptoms of depression and agitation respectively.At last,Activity of Daily Living Scale(ADL)was used to evaluate the patients' instrumental activities of daily living(IADL)and physical selfmaintenance ability(PSMS).All patients were completed magnetic resonance scanning(MRI)which was performed on a 3.0 T MR scanner(Philips Achieva).A clinician trained in rating ischemic white matter changes,and who had been blinded to clinical and functional data,rated the white matter changes on the T 2 axial and/or FLAIR images,Another senior doctor reviewed the results.The patients were divided into three groups according to the categorization of the patients by PWMH and DWMH severities respectivly.Baseline demographics compared by a chi-square test and an analysis of variance(ANOVA).We administered an analysis of variance(ANOVA)to compare the cognitive function,NPI scores,ADL scores,CSDD scores and CMAI scores among the groups.We used covariance analysis to adjust for confounding factor,adding age and hypertension as covariates.Some of the data among the three groups are not normal distribution,so we used the maximum likelihood estimation of the generalized linear model to compare the difference of scores one by one.Results:1.There was no difference in coronary heart disease,diabetes mellitus,smoking,sex,education level among the three groups,Age(p=0.001)and the morbidity rate of hypertension(p=0.001)were significantly different between the DWHM groups.After multiple comparisons,the age in mild group D1 was less than that of moderate group D2(P=0.012)and severe group D3(P=0.001).The morbidity rate of hypertension in moderate group D2(P=0.01)and severe group D3(P =0.001)is higher than that in mild group D1.2.In three groups by severity of PWMH,there were significant differences between the age(P=0.022)and hypertension(P=0.037).The age of the mild group P1 was less than that of the severe group P3(P=0.007)according paired comparison.The results of pairwise comparison showed that the morbidity rate of hypertension in severe group P3 was higher than that in mild group P1(P=0.013).3.There were statistical differences among the DWHM three groups in the total scores of CDR?ADL?IADL?PSMS and CSDD,however,no differences were found with regard toMMSE scores ?NPI scores and CMAI scores according to DWMH level.There was no significant difference in CDR scores(P=0.682)and IADL scores(P=0.057)among three groups after conducting covariance analysis or maximum likelihood method of generalized linear model adjusting for hypertension and age.but IADL score showed the tendency for difference(P=0.057).While,the difference of PSMS scores among the three groups was still significant(P =0.046)after adjusting age and hypertension as covariables.The results of paired comparison showed that the PSMS in the severe group was significantly higher than that in the mild group,Which means the worse of the patient's physical ADL.,At the same times,the ADL scores(P=0.032)and the CSDD scores(P=0.029)between three groups was also significant difference after adjusting.The ADL scores in severe group(D3)was significantly higher than that in mild group D1(P < 0.05)and moderate group D2(P =0.019)according multiple comparisons.The CSDD scores in severe group(D3)was higher than that in mild group D1(P=0.001).4.According to PWMH level,the total score of CDR?MMSE?NPI?CSDD and CMAI among three groups which exhibited statistically significant difference.but no differences were found with ADL,IADL,PSMS scores.The difference of MMSE scores among the three groups was still significant(P =0.006)after adjusting age and hypertension as covariables.The MMSE scores in severe group(P3)was significantly less than that in mild group P1(P =0.001)and moderate group P2(P =0.035)according multiple comparisons.After adjusting for age and hypertension there was no significant difference in the total score of CSDD between groups(P=0.064),NPI score showed the tendency for difference(P=0.062).The differences in the CMAI scores disappeared after the introduction of covariates(P=0.706).5.There was no significant difference in frequency of BPSD symptoms among DWMH groups.While,the frequency of aberrant motor behavior in PWMH group were significantly different(P=0.011).The frequency of moderate group(P2)was significantly higher than that in mild group P1(P=0.007)according multiple comparisons.There was no significant difference in the frequency of abnormal movement between group P3,P2(P=0.07)and group P3P1(P=0.399).Conclusions:1.Mean age and the morbidity rate of hypertension were different among the three WMH groups.The age and the morbidity rate of hypertension in the DWMH moderate and DWMH severe group were higher than those in the DWMH mild group,and the morbidity rate of hypertension in the PWMH severe group was higher than that in the PWMH mild group.The results showed that age,hypertension were positively correlated with the WMH.2.PWMH was revealed to be closely related with cognition,which the MMSE in the patients with severe PWMH(P3)were significantly lower than those in the moderate PWMH(P2)and the mild PWMH(P1).However,the DWMH was not correlated with cognitive function.3.NPI score showed the tendency for difference in PWMH groups,We can speculate that the higher severity of PWMH may lead to more severe neuropsychiatric symptoms.4.There was independent correlation between PWMH and aberrant motor behavior of neuropsychiatric symptoms.The frequency of aberrant motor behavior in moderate group(P2)was significantly higher than that in mild group(P1),.However,there was no significant difference between severe group(P3)and mild group(P1)as well as moderate group(P2).5.The CSDD scores in severe DWMH(D3)was higher than that in mild DWMH(D1),the higher severity of DWMH may lead to more severe depression.The results were consistent with those of elderly adults with depression.There was no significant difference in depression score between the groups in PWMH.6.The WMH is associated with daily living ability.More serious white matter lesion indicates that the patient's daily living ability is worse,DWMH was associated with IADL ?PSMS and ADL in AD patients.PWMH may associated with IADL,which need more research to confirm.