Clinicopathological Study Of Subcortical Vascular Cognitive Impairment

With the development of neuropathology study of dementia, it is found that up to 1/3 ofdementia patients exists considerable cerebrovascular pathology. Vascular factors as a causeof dementia has become a hot spot following research on Alzheimer's disease. Thedifference is that cognitive impairment, vascular cognitive impairment may be able to earlyprevention, or a decline in cognitive function can improve, it has been more and moreattention, vascular factors controllability for the treatment of dementia provides a new wayof thinking.Vascular cognitive impairment, including a series of cerebrovascular disease associatedwith different degrees of cognitive impairment, and gradually replaced the concept ofvascular dementia. Even though international scholars have developed the definition ofVCI, but its concepts and the meaning of vague, differences exist. VaD diagnostic criteriado not fully include the scope of VCI and therefore can not realize the existence ofcognitive impairment of vascular dementia but is not reached to the level of dementia(VCIND), which is a mild VCI status, suitable for secondary prevention. Currently requiredto establish a uniform standard clinical practice to study encountered many VCI. This studycompared subcortical vascular dementia and non-vascular dementia patients but has similardamage in subcortical pathology to observe of the possible mechanisms of vascularcognitive impairment and hope to take early clinical diagnosis.of VCI step by step.PartⅠThe neuropathology characteristics of pure SIVDObjectives: The aim of this study is to describe in detail the neuropathology characteristicsof patients with SIVD from normal control cases.Material and Methods:We examined 12 patients (men 7, age76.67±10.59 years) in whomno clue of other type of dementia was found by the standard staining techniques includinghematoxylin-eosin, Kluver-Barrera, and Gallyas-Braak combined with Luxol fastblue/cresylviolet, and alpha-synuclein (AS), phosphorylated tau (AT8) and beta-amyloidprotein immunostainings. We compared the demyelination and axonal loss in the parietal,frontal, temporal lobes and cerebellum of the 9 pure SIVD cases with the matched healthycontrols. Semi-quantitative comparison of Kluver-Barrera staining was performed. Thelevels and distribution of the myelin marker, myelin basic protein (MBP), the neurofilament(NF) and glial fibrillary acidic protein (GFAP) were measured using immunocyto chemistry.Results: Our results indicated that the white matter (WM) damage in SIVD wassignificantly more prominent in the parietal and frontal lobes than in the cerebellum andtemporal lobes. The grading scores by Kluver-Barrera staining in thefrontal(2.7±0.49)/parietal(2.4±0.66) subcortical reagions were significantly higher than those in the temporal(1.2±0.71, p＜0.05) and the cerebellar (1.5±1.0, p＜0.05) regions.Furthermore, the frequency of axonal loss was significantly higher in SIVD than in thecontrol brains. Within the SIVD group, the grading scores of axonal loss in the parietal werealso significantly higher than those in the the cerebellar regions, parietal regions.Our studyalso showed that the GFAP-positive astrocytes were significantly increase in number andenlarged in size in the subcortical WM, especially in the frontal lobe.Conclusions: The frontal and parietal lobes are more severely affected than the cerebellumand temporal lobes in pure SIVD. Prefrontal reactive astrocytes proliferation significantly,while the temporal lobe microglia cells were less hyperplasia.PartⅡThe subcortical vascular damage of Alzheimer's disease (AD)Objectives: To study the white matter pathology characteristics of AD accompanyingsubcortical vascular lesions, and its differences with pure SIVD groups.Material and Methods: we selected Pathological specimens of ten AD patients withsubcortical vascular lesions. Routine (HE and KB) and special staining (CD68, GFAP, andvascular stain azan)were performed and compared with SIVD patients in part 1.Results: KB staining showed that the extent of myelin loss of AD patients in frontal andparietal lobe was significantly than in temporal lobe and cerebellum, while NF stainingshowed axonal loss of the temporal lobe was also serious, as opposed to the cerebellumwere also significant differences. The reactive astrocytes in each lobes were basicallysimilar. Neuropathological characteristics between AD patient group and pure SIVD groupshowed: KB myelin staining showed SIVD group is significantly more serious damagedthan in AD group; microglia cell hyperplasia was significantly in temporal lobe SIVDcompared with AD group.Conclusion: Axonal loss was more serious in frontal and parietal lobe than the cerebellumand temporal lobe in AD with subcortical vascular damage patients. More Microglia cellproliferation was observed in the temporal lobe in SIVD group. Microglia cell may beinvolved in AD pathology.PartⅢThe Cholinergic system in vascular cognitive impairmentObjectives: Further compare the selective pathway (cholinergic pathway) betweenSIVD, VCIND and AD patients: the similarities and differencesMaterial and Methods: Select SIVD group (12 cases), AD group (16 cases) and VCIND group (3 cases), staine assessed cholinergic pathway changes among the three groups. Blindreview the cholinergic pathway damage score (Cholinergic Pathways HyperintensitiesScale, CHIPS) of MRI, compared with the pathological studies.Results: Pathology showed up on cholinergic pathway inter-group differences weresignificant in SIVD group and AD group, proposed in subcortical vascular dementiapatients the cholinergic pathway damage was more severe than AD group.VCIND patients,although the small sample of cases, the data also showed difference to SIVD group,suggesting that the extent of damage in cholinergic pathway and the degree of cognitiveimpairment may be related to each other. CHIPS score on MRI and pathological study werecoincided.conclusion: Cholinergic pathway damage are possibly important reasons of subcorticalvascular cognitive impairment. CHIPS score can be used in future clinical practice to earlyscreen vascular cognitive impairment patients.Conclusion1. Pure subcortical vascular dementia patients were with varying degrees of lobe damage.Axonal loss in frontal and parietal lobe were more serious than in the cerebellum andtemporal regions. Prefrontal reactive astrocytes proliferated significantly2. Axonal loss was more serious in frontal and parietal lobe than the cerebellum andtemporal lobe in AD with subcortical vascular damage patients. More Microglia cellproliferation was observed in the temporal lobe in SIVD group. Microglia cell may beinvolved in AD pathology.3. Acetylcholine system deficiencies were not only the characteristic changes in AD patientsbut also exist in the VCI pateints (cholinergic pathway fiber loss), and was probably one ofthe important mechanisms in VCI development.4. Cholinergic pathway damage are possibly important reasons of subcortical vascularcognitive impairment. CHIPS score can be used in future clinical practice to early screenvascular cognitive impairment patients.