Cognitive Functional Characteristics Of Parkinson’s Disease Subtype And Study Of Resting State Functional Magnetic Resonance Imaging

Background and purposeParkinson’s disease(PD) is a progressive neurodegenerative disorder that is characterized by motor and nonmotor symptoms. The classic motor symptoms include tremor, rigidity, slowness of movements, and postural instability, which are well know. However, the nonmotor symptoms, which are shown even before the motor symptom and along with the whole course of disease, are easy to be ignore. Nowadays, with the awareness of the nonmotor symptoms, more and more research focus on the cognition impairment. Cross-sectional studies have found that the average incidence of PD with mild cognitive impairment(PD- MCI) was 27%, and scholars think that PD- MCI is the transition stage of PD with dementia(PDD), and in the whole course of PD-MCI the incidence of PDD rates up to 70 ~ 80%. The clinical symptoms of PD are very complicated,there is a growing number of studies that have found a great difference in the course speed of PD and clinical characteristics, and the traditional diagnostic criteria can not explain the complexity of the clinical symptoms of PD, Alonso et al first sum this complexity to surprisingly heterogeneous of PD, and put forward the concept of PD subtype. At present, Parkinson’s disease is divided into tremor-dominant(TD) and postural instability and gait difficulty(PIGD) has been international consensus. The clinical findings were different from the typical symptoms of different subtype,and the declare rate of cognitive function and prognosis has obvious difference between different subtype, although the cognitive dysfunction was related to the age and the severity of motor symptoms. Evidence shows thatPIGD is risk factor of PDD, although cognitive impairment is related to age and severity of motor symptoms. Thus someone believed that different subtypes of PD have a different neural mechanisms. This study uses cognitive assessment scale to assess cognitive characteristics of PD subtypes and PD subtype with MCI, combined with analysis of regional homogeneity of resting state fmri(Re Ho) brain function activities of subtype of PD with MCI in the resting state, to explore the differences of nerve activity between PD subtype of PD with MCI, as well as the application value of local consistency analysis in the research of PD subtype, and provide a theoretical basis for early intervention of PD subtype of disease progression and delay the occurrence of PDD.Materials and Methods1. Participants subtype of PD: 27 tremor-dominant(TD) patients, 33 postural instability and gait difficulty(PIGD) patients; subtype of PD with MCI patients: 19 TD with MCI patients, 23 PIGD with MCI patients; 25 healthy control(HC). All the participants are age-, sex- and educaton-matched.2. Montreal cognitive assessment(Mo CA) and mini-mental state examination(MMSE) were administered to measure the cognition. Hamilton depression rating scale,HAMD was administered to measure the severity of depression. Part II and III of the Unified Parkinson’s Disease Rating Scale(UPDRS) were administered to measure the daily living ability and motor performance. The Hoehn and Yahr scale were used to assess the disease staging of PD; Trail Making Test-A(TMT-A), 15 points Clock Drawing Test(CDT), Verbal fluency test(VFT), Rey’s Auditory Verbal Learning Test(RAVLT) and Clock copying to assess all the cognitive domain of subtype of PD with MCI.3. MRI data acquisition: MRI images were acquired using a 3.0 T Siemens Tim Trio whole-bodyMRI system(Siemens Medical Solutions, Erlangen, Germany). Brain magnetic resonance images(T1- and T2-weighted images) were inspected by an experienced neuroradiologist, and no gross abnormalities were found in any of the participants. The functional imaging data were collected transversely by using an echo-planar imaging(EPI) sequence. Three-dimensional T1-weighted anatomical images were collected sagittally using the following volumetric 3D magnetization-prepared rapid gradient-echo(MP-RAGE) sequence each subject.4. Functional image preprocessing: Preprocessing was performed using the SPM8.5. Statistical analysis: Demographic characteristics were analysed using SPSS20.0. Three groups of samples were analysed using single factor analysis of variance or variance with nonparametric test when data does not conform to the normal homogeneity; Two groups of samples were analysed using t test; Count data using chi-square test, ranked data using Kruskal Wallis H; P < 0. 05 was considered statistically significant. Resting state f MRI data were analysed using SPM8 software, the Re Ho value TD group, PIGD group and HC group were analysed two sample t test respectively, Alpha Sim were used to correct for multiple comparisons. P < 0. 05 for statistically significant.Result1. Cognitive function characteristic of patients with subtype of PD(1) Comparison of demographic characteristicsThere was no significant difference among the three groups in terms of gender, age, or educational level(P>0.05), HAMD score of HC was lower than two subtypes of PD groups(P<0.01), There was no significant difference between the TD-PD and PIGD-PD groups in terms of the duration of disease, onset age, UPDRS-II and-III score(P>0.05). Hoehn and Yahr scale score of PIGD was higher than TD group(P<0.05).(2) Comparison of Mo CA and all the domain scoreThree groups comparison: Significant differences in the Mo CA scores and visual space and executive function, attention, language, abstract and delayed memory, orientation between two subtypes of PD and HC group were observed(P < 0.01). TD and HC group comparison: Mo CA scores and visual space and executive function, language, abstract and delayed memory the four sub items of TD group are lower than the HC group(P < 0.01). PIGD with HC group comparison: MoCA scores and visual space and executive function, attention, language, abstract and delayed memory, orientation the six sub items of PIGD are lower HC group(P < 0.01); TD and PIGD group comparison: Mo CA scores and delay memory, orientation of PIGD group is lower than the TD(P < 0.05).(3) Comparison of MMSE and all the domain scoreThree groups comparison: Significant differences in the MMSE score and orientation, attention calculation, delay memory, visual spatial ability(P < 0.05) the between two subtypes of PD and HC group were observed. TD and HC group comparison: MMSE score of TD group are lower than the HC group(P < 0.05). PIGD with HC group comparison: MMSE score and orientation, attention calculation and delayed memory, visual spatial ability the four sub items of PIGD are lower than HC group(P < 0.01). TD and PIGD group comparison: MMSE score and orientation, attention calculation of PIGD group are lower than TD group(P < 0.01).(4) Comparison of incidence of cognitive impairment in two subtypes of PDThere is no statistical difference between incidence of MCI in two subtypes(P > 0.05); The incidence of PDD is higher in PIGD group than the TD group(P < 0.05).2. Cognitive function characteristic of patients with subtype of PD with MCI(1) Comparison of demographic characteristicsThere was no significant difference among the three groups in terms of age, gender, or educational level(P>0.05). HAMD score of HC was lower than two subtypes of PD with MCI groups(P<0.01). There was no significant difference between the subtypes of PD with TD-MCI and PIGD-MCI groups in terms of the duration of disease, onset age,Hoehn and Yahr scale score, UPDRS-II and-III score.(2) Comparison of Mo CA and all the domain scoreThree groups comparison: Significant differences in the Mo CA scores and visual space and executive function, named, attention, language, abstract and delayed memory, orientation between two subtypes of PD and HC group were observed(P < 0.05). TD and HC group comparison: Mo CA scores and visual space and executive function, named, attention, language, abstract and delayed memory, orientation the seven sub items of TD group are lower than the HC group(P < 0.05). PIGD with HC group comparison: Mo CA scores and visual space and executive function, attention, language, abstract and delayed memory, orientation the six sub items of PIGD are lower HC group(P < 0.01); TD and PIGD group comparison: There was no significant difference in MoCA scores and all the domain score(P>0.05).(3) Comparison of MMSE and all the domain scoreThree groups comparison: Significant differences in the MMSE score and orientation, attention calculation(P < 0.01) between two subtypes of PD and HC group were observed. TD and HC group comparison: MMSE score and orientation, attention calculation the two sub item of TD group are lower than the HC group(P < 0.05). PIGD with HC group comparison: MMSE score and orientation, attention calculation the two sub item of PIGD are lower than HC group(P < 0.01). TD and PIGD group comparison: There was no significant difference in MMSE score and all the domain score(P>0.05).(4) Comparison of impaired cognitive domains in two subtypes of PD with MCIThere were 19 patients in TD-MCI group, 12 patients with single-domain damage type(63.16%), 7 patients with multi-domain damage type(36.84%); There were 23 patients in PIGD-MCI group, 6 patients with single-domain damage type(26.09%), 17 patients with multi-domain damage type(73.91%);There were significant differences in the field of cognitive impairmentand in two subtypes of PD with MCI groups.(P < 0.05).3. Resting state functional magnetic resonance imaging of PD subtype with MCI(1) Comparison of Re Ho values between TD-MCI and HC group.TD-MCI patients, relative to healthy controls, had increased Re Ho in the right cerebellum posterior lobe, bilateral superior frontal gyrus and right precentral gyrus and decreased Re Ho in right posterior cingulate cortex, left lingual gyrus.(2)Comparison of Re Ho values between PIGD-MCI and HC group.PIGD-MCI patients, relative to healthy controls, had increased Re Ho in the right middle frontal gyrus and left superior frontal gyrus and decreased Re Ho in right posterior cingulate cortex,left lingual gyrus and left middle temporal gyrus.(3)Comparison of Re Ho values between two subtypes of PD with MCI.PIGD-MCI patients, relative to TD-MCI group, had increased Re Ho in right inferior parietal lobule and decreased Re Ho in right superior frontal gyrus, right precentral gyrus and right cerebellum posterior lobe.Conclusion1. Two subtypes of PD both have cognitive dysfunction, PIGD subtype have poorer overall cognitive function, more impaired cognitive domain and greater severity of impairment than TD, PIGD subtype had a significantly higher incidence of PDD than TD group,PIGD subtype may be the key or important risk factor for the pathogenesis of PDD.2. Mo CA and MMSE cognitive screening scale can not be timely and effectively reflect the differences of cognitive function between different subtypes of PD with MCI. cognitive domain detection scale can resolution the cognitive areas damaged type differences between subtypes of PD with MCI, TD subtype was dominated by single domain, while the PIGD subtype was dominated by multi domain.3. Abnormal active brain region between subtypes of PD with MCI patients were different,and there are differences between brain regions with different subtypes of PD related with movement disorders characteristics, resting state local consistency analysis method can sensitively find the difference of neuron activity between PD subtype in early cognitive impairment stage, it can effectively reflect the functional activity of PD subtype with MCI, and provide reliable basis for the study on the physiological mechanism of the nerve of PD subtype.