The Study On The Relationship Between Parkinson Disease With Dementia And Alzheimer Disease

Objective:Parkinson disease (PD) and Alzheimer disease (AD) are the most common neurodegeneration disorders in the aged. There are overlaps in clinical characteristics between PD and AD. Dementia often happens in patients with PD, while extrapyramidal signs (EPS) are showed in patients with AD. In the past, PDD were regarded as subcortical dementia. However, recent studies showed that there were neuropathologic lesions of AD, such asβ-amyliod depositions in the cortex of PDD. So it was recommended that PDD should be classified into three types, which were subcortical type, AD type and lewy body type. The relationship between Parkinson disease with dementia and Alzheimer disease, being concomitant or the different courses of neurodegeneration, attracted our attention and made us contemplate.In the present study, detailed clinical investigations and neuropsychological tests were performed on PD and AD patients to study the incidence of PDD and EPS in AD, and to explore their relationship during the courses of diseases and the similarities or the differences in neuropsychological characteristics. As Hyperhomocysteinemia being a potential pathogenesis of neurodegeneration disorders, the plasma Hcy level and cystathionine B synthase gene 844 insertion 68bp fragment(CBS844ins68), N⁵,N¹⁰-Methylenetetrahydrofolate reductase (MTHRF) gene C677T polymorphisms were detected to investigate the roles of Hcy and metabolic enzyme gene polymorphisms in the pathogenesis of AD and PDD. Also, the cerebral metabolism of glucose in PDD and AD was studied to learn the location and the degree of degenerated neuron indirectly. So we can study the relationship between PDD and AD from the aspect of pathophysiology.Methods and materials: 336 PD patients were enrolled and given detailed clinical investigations, physical examination and mini-mental state examination, while 112 AD patients were given investigations about the occurrence of EPS. 60 AD, PDD, PD patients and controls respectively were performed tests on executive functioning, including verbal fluent test, trail making test A, Stroop test and clock drawing test (CDT). MTHRF C677T, CBS844ins68 and ApoE gene polymorphisms of 102 sporadic AD(sAD) patients, 81 PDD patients, 133 non-demented PD patients and 105 healthy individuals were analyzed using polymerase chain reaction or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Levels of plasma Hcy and serum folic acid and vitamin B₁₂ of 30 cases of each group were detected. The correlations between these factors and the incidence of PDD or AD were analyzed respectively. 21 AD patients, 20 PDD patients and 8 PD patients were performed ¹⁸F-FDG PET imaging at rest state. Statistical parametric mapping (SPM) was used to investigate regional cerebral metabolic rate of glucose (rCMRglc). What's more, 23 cases of patients with other neurodegeneration dementia, including 8 DLB, 6 FTD, 7 PSP and 2 CBD were diagnosed and differentiated.Results:The incidence of PDD was 30.36 percent. There was significant positive correlation between MMSE score and the years of education, significant negative correlation between MMSE score and the degree of hallucination, the onset age, motor dysfunction. The incidence of EPS in AD patients was 29.51 percent. The risk factors were the age of patients and the course of AD. The occurrence of PDD was affected much more by environmental factors, while the occurrence of AD was affected more by genetic and vascular factors. The memory impairments of PDD were less than that of AD, but the executive functioning and visuospatiaI disturbance were more serious than that of AD. However, the attention, as well as visuospatial and executive functioning was impaired even in non-demented PD. Among the instrument detecting executive functioning, verbal fluent test, trail making test A and CDT showed higher sensitivity, while Stroop test showed higher specificity. Among the four groups, there was no significant difference in the distributions of MTHRF C677T and CBS844ins68 gene polymorphism. Both the ApoE geneε4 allele frequency of sAD and PDD were significantly higher than that of controls and non-demented PD. However, MTHRF C677T and ApoE may have a synergetic role on the occurrence of sAD or PDD. Levels of plasma Hcy in sAD and PDD were significant higher than that of controls and non-demented PD, and levels of serum folic acid and vitamin B₁₂ were significant lower than that of controls and non-demented PD. Both in group sAD and PDD, there was significant negative correlation between MMSE scores and the levels of Hcy, no correlation between MMSE scores and the levels of serum folic acid and vitamin B₁₂. In group PD and PDD, there was significant positive correlation between Hoehn and Yahr scores and the levels of Hcy, no correlation between MMSE scores and the levels of serum folic acid and vitamin B₁₂.Compared to controls, the rCMRglc in AD included bilateral parieto-temporal association cortex, frontal cortex, precuneus and posterior cingulate cortex. The hypometabolism areas in early onset AD appeared much more extensive and serious than that in late onset AD. The hypometabolism areas in moderate and severe AD were much extensive than that in mild AD, especially on frontal cortex. The metabolism of subcortical structures such as basal ganglion and thalamus decreased in severe AD.Compared to controls, the rCMRglc in PD decreased only in bilateral posterior parietal cortex, while the rCMRglc in PDD decreased in bilateral parietotemporal association cortex, frontal cortex, occipital cortex and subcortical structures, including basal ganglion and thalamus. However, when all the PDD were divided into hallucination group and memory impaired group according to the scores and the onset time of hallucination, it could be found that the hallucination group showed significant hypometabolism in parietooccipital cortex, while the memory impaired group showed significant hypometabolism in bilateral parietotemporal association cortex and precuneus, which was similar with AD. The rCMRglc in DLB decreased in bilateral occipital cortex, posterior parietal cortex, temporal cortex, basal ganglion and thalamus. The rCMRglc in FTD decreased mainly in bilateral frontal cortex, parietal cortex and basal ganglion and thalamus. In PSP, the decreased areas included bilateral frontal cortex, cingulate cortex, basal ganglion, thalamus and mesencephalon, And in CBD, the decreased areas included contralateral parietal cortex, frontal cortex, cingulate cortex, basal ganglion and thalamus.Conclusions:There are much more overlaps of clinical characteristics between PD and AD. About 30 percent patients show both dementia and EPS. The memory impairments of PDD are less than that of AD, while the executive functioning and visuospatial disturbance are more serious than that of AD. The incidence of hallucination in PDD is much more than that in AD.Hyperhomocysteinemia may be a risk factors of sAD and PDD. And the levels of Hcy are significant correlated with the cognitive impairment and motor disturbance. There is no directly correlation between MTHRF C677T and sAD or PDD, so is CBS844ins68. ApoE geneε4 allele carrier is a risk factor of sAD or PDD. MTHRF C677T and ApoE may have a synergetic role on the occurrence of sAD or PDD.The rCMRglc in AD decreases in bilateral parieto-temporal association cortex, frontal cortex, precuneus and posterior cingulate cortex. Serious hypometabolism in frontal cortex may be a maker of mild AD progressed to moderate and severe AD. The metabolism of subcortical structures, such as basal ganglion and thalamus decreases in severe AD.The rCMRglc in PDD decreases in bilateral parietotemporal association cortex, frontal cortex, occipital cortex and subcortical structures, including basal ganglion and thalamus, which suggests that PDD is more than subcortical dementia but cortical dementia. Hallucination dominant patients show significant hypometabolism in parietooccipital cortex, while the memory impaired group show significant hypometabolism in bilateral parietotemporal association cortex and precuneus, which is similar with AD. The reduction of metabolism in bilateral occipital cortex can differentiate DLB from AD, but hardly from PDD. In FTD, the hypometabolism areas are mainly in bilateral frontal cortex. The reduction of metabolism in mesencephalon and basal ganglion is the characteristics of PSP. And in CBD, the decreased areas are asymmetric, mainly in contralateral parietal cortex and frontal cortex, as well as basal ganglion and thalamus. FDG PET is a valuable means to diagnose and differentiate neurodegeneration dementia, and SPM is a reliable and useful method.