A Preliminary Study On The Relationship Between Vascular Risk Factors And Dementi

Part 1.Vascular Risk Factors in Dementia with Various Etiology[Background and objective]Previous studies indicated vascular risk factors factors including hypertension,diabetes,hyperlipidemia and smoking are related to all-cause cognitive impairment.vascular risk factors increase the risk of dementia and improve its development.Dense focal lesions in basal ganglia,called ’cheese sign’,was seen as a marker of small vascular mechanism,they can also be detected in patients with degenerative diseases such as AD and FTLD.The aim of this study was to describe the incidence rate of hypertension,diabetes,hyperlipidemia and stroke in different groups,and to describe the characteristics and risk factors of cheese sign based on the our hospital dementia cohort.[Methods]This study was a retrospective study.Patients were enrolled consecutively from the dementia cohort,who visited the dementia clinic of our hospital from 2007 to 2022.(1)Dementia cohort was classified into different groups based on various causes including AD,FTLD,vascular cognitive impairment and others.The incidence rates of vascular risk factors and cheese sign in groups were described.(2)According to the presence or absence of cheese sign,people with all-cause dementia were divided into two groups.We use semiquantitative method to calculate the number of different lesions(basal ganglia hyperintensities,perivascular spaces,lacunae,and chronic infarcts)in basal ganglia.The risk factors and composition of cheese sign were identified.[Results]A total of 812 patients were included,133 diagnosed with biological Alzheimer’s disease,68 with FTLD,36 with probable/possible CAA,21 with definite CADASIL,and 95 with other CSVD.The prevalence of hypertension in AD,FTLD,CAA and CADASIL group were 27.7%,20.59%,44.44%and 42.86%;the prevalence of diabetes were 9.02%,10.59%,8.33%and 4.76%;the prevalence of hyperlipidemia were 27.82%,22.06%,19.44%and 9.53%.Stroke happened in 3.01%AD and 5.88%FTLD patients.The detection rates of cheese sign were 2.25%in AD,8.82%in FTLD,9.25%in CADASIL group and highest in CAA group(27.8%)and other CSVD group(50.52%).The risk factors of cheese sign were age,hypertension and cerebrovascular events.It mainly consists of basal ganglia hyperintensities and perivascular spaces,occasionally lacunae and chronic infarcts.We established a grading method for cheese sign.Basal ganglia hyperintensity remains the main component in different degrees(mild group 69.96%,moderate group 62.58%,severe group 57.11%).However,the proportion of perivascular spaces was positively correlated with the degree of cheese sign(mild group 22.53%,moderate group 29.94%,severe group 37.37%,P=0.006).There was no significant difference in proportion of lacuna/infarction among the three groups.[Conclusion]Vascular risk factors including hypertension,diabetes and hyperlipidemia and stroke can be seen in degenerative diseases.The prevalence differs in various dementia groups.The prevalence of hypertension was 27.7%-44.4%in AD,FTLD and non-atherosclerotic CSVD.Cheese sign can be seen in cerebrovascular diseases and other degenerative disorders.The main risk factors of cheese sign were age,hypertension,and cerebrovascular events.The main composition of cheese sign was basal ganglion hyperintensity,and the proportion of perivascular spaces was related to the degree of cheese sign.This study no longer supports the simple equivalence of cheese sign to dense perivascular spaces.Part 2.Effect of Vascular Risk Factors in Presenile Alzheimer’s Disease[Background and objective]Vascular risk factors(hypertension,diabetes,hyperlipidemia,etc.)are main adjustable risk factors of AD.These factors influence cerebral perfusion,blood-brain barrier destruction,vascular microstructure damage,β-Amyloid clearance and other inflammatory mechanisms,then promote onset and course of AD.Previous studies indicated heterogeneity in early and late-onset AD.The role of vascular risk factors in early-onset AD remains unclear.The purpose of this study was to compare the clinical and biological characteristics of presenile AD patients with and without vascular risk factors.[Methods]This study is retrospective.Biological diagnosis was performed on AD patients who met the 2011 NIA-AA clinical diagnostic criteria from cohort who visited the Dementia Clinic of our hospital from 2007 to 2022:1)Cerebrospinal fluid(CSF)biomarkers(Aβ 42,Aβ40,T-tau,P-tau)detection;or 2)amyloid protein PET;or 3)Whole genome sequencing screening for APP/PSEN1/PSEN2 mutations.Patients whose CSF biomarkers met the criterion of AD pathological changes or carrying APP/PSN1/PSN2 pathogenic mutations were enrolled for further study of vascular risk factors.Detailed clinical data were collected and head MRI performed.Imaging data were analysed including cerebral small vessel disease markers,MTA and Koedam score.Test of Cerebrospinal fluid biomarkers(Aβ-42,T-tau,P-tau)and 3D-T1 imaging for brain volume measurement were performed in partial patients.These patients were divided into two groups according to the presence or absence of vascular risk factors(hypertension,diabetes,hyperlipidemia and stroke).The age of onset,baseline cognition,levels of cerebrospinal fluid markers,and imaging characteristics were compared.[Results]A total of 133 AD patients were enrolled,of which 108 were early-onset(48 males and 60 females).46 patients with vascular risk factors(positive group),with an average onset age of 55.03±5.86 years;62 cases without vascular risk factors(negative group),with an average onset age of 54.41±6.20 years.Negative group and positive group showed no significant difference in gender,age,course of disease,education,cognitive examination,APOE genotype and imaging features.96 patients performed lumbar puncture,the levels of Aβ-42,T-tau,P-tau and ratio of T-tau/Aβ were similar in negative and positive groups.Volumes of various regions of brain and CSF were measured based on 3D-T1 imaging.The volume of gray matter in the negative group was smaller than that in positive group.The proportion of CSF volume including peripheral CSF(P=0.006)and the third ventricle(P=0.042),increased significantly in negative group than positive group.[Conclusion]Hypertension,diabetes,hyperlipidemia and stroke showed no significant impact on clinical feature,cerebrospinal fluid biomarkers and imaging characteristics of early-onset AD.AD patients without vascular risk factors had larger volume of cerebrospinal fluid,peripheral cerebrospinal fluid and third ventricle.Part 3.Effect of Vascular risk factors in Frontotemporal lobar degeneration[Background and Objective]Frontotemporal lobar degeneration(FTLD)is one of the most common causes of presenile dementia.About 40%of FTLD are caused by genetic mutations,and genetic factors play an important role in the pathogenesis of FTLD.The mechanism and modified risk factors of sporadic FTLD are still unclear.Age related Vascular risk factors factors are involved in many neurodegenerative disorders like AD and DLB,but there are few studies in FTLD.The purpose of this study was to explore the impact of vascular risk factors in the FTLD based on the Our hospital dementia cohort.[Method]This study is a single center retrospective study.Patients met probable bvFTD and imaging-confirmed PPA diagnosis were enrolled,some were definite FTLD with pathogenic mutation.Detailed general data and medical history were collected for all patients,and neuropsychological and imaging assessments were performed.Some patients underwent lumbar puncture for CSF marker test.FTLD patients were divided into two groups according to whether they were complicated with hypertension,hyperlipidemia,diabetes and cerebrovascular events.The clinical and biological characteristics were compared between two groups.[Results]A total of 66 patients with FTLD were enrolled in this study,with an average onset age of 55.94±10.11 years.34 cases were diagnosed with bvFTD and 32 cases with PPA,and 6 cases were complicated with amyotrophic lateral sclerosis.28 patients with Vascular risk factors were divided into positive group and 38 cases without Vascular risk factors negative group.The average age at onset in negative group was younger(53.76 ±11.39 years old,P=0.041),the impairment of daily living ability was more severe(40.26± 12.23,P=0.049).There were no differences in Fazekas score,perivascular space degree,MTA,and Koedam score between the two groups.48 patients performed lumbar puncture,average Aβ level was 710.5 ± 307.7 pg/ml,and T-tau 183.6(115.8,362.2)pg/ml.There was no difference in the levels of cerebrospinal fluid biomarkers between groups.Brain volume measurements were completed in 28 FTLD patients.Total brain volume and each lobar volume also showed no difference between the two groups.[Conclusion]There was no significant difference in cognitive impairment,cerebrospinal fluid biomarkers,imaging features related to cerebral small vessel disease,and brain volumes.Patients with vascular risk factors had smaller age at onset and higher ADL.The role of Vascular risk factors in FTLD needs further researches.