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1.
OBJECTIVES: To develop age-adjusted norms for white matter lesions (WML) and to differentiate dementia from mild cognitive impairment and normal aging. MATERIALS AND METHODS: 240 patients underwent a comprehensive clinical, neuropsychological and MRI examination. A scale was developed quantify WML in anatomically defined regions by rating size and frequency. FLAIR sequences were used to determine a global and a frontal score. The scores were correlated with the psychometric test results and the final clinical diagnosis: cognitively normal (CN), mild cognitive impairment (MCI), Alzheimer's Disease (AD), vascular dementia (VD). Age-adjusted curves for WML scores were calculated by means of a non-parametic smoothing method. RESULTS: WML scores of the whole cerebrum and the frontal lobe were significantly increased in vascular dementia as compared to CN, MCI and AD. Individual WML scores correlated significantly with age and neuropsychological test results. For the age range 55-72, the WML scores of VD were significantly different from those of CN, MCI and AD. CONCLUSIONS: Age-corrected WML load was significantly higher in vascular dementia as compared to MCI, AD and cognitively normals over a wide age range.  相似文献   
2.
OBJECTIVE: To explore the activities of daily living ADL performance profile of community-living people with dementia and to investigate its relationship with dementia severity. MATERIALS & METHODS: ADL performance of 86 subjects were evaluated using Barthel Index (BI), Lawton and Brody's Instrumental Activities Daily Living (IADL) and Assessment of Motor and Process Skills (AMPS). Dementia severity was measured by Clinical Dementia Rating (CDR). RESULTS: Subjects were able to perform most basic ADL (BI mean = 16.4) and some IADL (Lawton and Brody's IADL mean = 4.3). The AMPS process ability measure and the Lawton and Brody's IADL were significantly correlated with CDR (P < 0.01). CONCLUSIONS: Subjects with mild dementia were able to perform mostly all basic ADL and some IADL. The AMPS process ability measure and the Lawton and Brody's IADL could provide useful information on their ability to live independently in the community.  相似文献   
3.
OBJECTIVES: In order to explore factors associated with the development of dementia in Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), we systematically investigated the clinical evaluation of PD and DLB patients hospitalized in the Department of Neurology at Tottori University Hospital, Japan. RESULTS: There were 208 patients diagnosed as having PD and 39 patients diagnosed with DLB in this study. Of the patients with PD, 67 (32%) developed dementia and only five PD+ patients were considered to have cognitive impairment attributable to Alzheimer's disease (AD) or vascular dementia (VaD). Fifty-four (81%) PDD patients had visual hallucinations (VH) with or without cognitive fluctuation. The onset age of parkinsonian motor symptoms of patients with PD dementia (PDD) did not differ from that of PD patients without dementia. There was a significant inverse correlation between the onset age of motor symptoms in PD and the onset of their dementia in PDD. Seventy-five (36%) patients with PD had experienced VH and most of the PDD patients had experienced VH within 1 year before or after diagnosis of PDD. CONCLUSIONS: These results indicate that aging and VH are important factors associated with dementia in PD.  相似文献   
4.
OBJECTIVE: Dementia occurs frequently in patients with Parkinson's disease (PD). However, the nature of the dementing process remains controversial. We evaluated various cognitive functions in patients with PD, compared fractional anisotropy (FA) values between PD patients with and without dementia. METHODS: Thirty-seven consecutive patients with Hoehn-Yahr stage III or IV PD participated in this study. Patients were divided into two groups: (i) PD with dementia group (PDD) and (ii) PD without dementia group (PDND). There were 11 PDD and 26 PDND cases. Ten controls were also studied. RESULTS: The PDD group showed significant FA reduction in the bilateral posterior cingulate bundles compared with PDND. FA values in the left posterior cingulate bundle showed significant correlations with many cognitive parameters. INTERPRETATION: Our results showed that the posterior cingulate areas play some important roles in the dementing process in PDD. However, as the pathological processes responsible for dementia in PD patients may be multifaceted, further studies are necessary.  相似文献   
5.
Mutations in Tau cause the inherited neurodegenerative disease, frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known coding region mutations cluster in the microtubule-binding region, where they alter the ability of tau to promote microtubule assembly. Depending on the tau isoforms, this region consists of three or four imperfect repeats of 31 or 32 amino acids, each of which contains a characteristic and invariant PGGG motif. Here, we report the novel G335S mutation, which changes the PGGG motif of the third tau repeat to PGGS, in an individual who developed social withdrawal, emotional bluntness and stereotypic behavior at age 22, followed by disinhibition, hyperorality and ideomotor apraxia. Abundant tau-positive inclusions were present in neurons and glia in the frontotemporal cortex, hippocampus and brainstem. Sarkosyl-insoluble tau showed paired helical and straight filaments, as well as more irregular rope-like filaments. The pattern of pathological tau bands was like that of Alzheimer disease. Experimentally, the G335S mutation resulted in a greatly reduced ability of tau to promote microtubule assembly, while having no significant effect on heparin-induced assembly of recombinant tau into filaments.  相似文献   
6.
The routine diagnosis of argyrophilic grain disease is fraught by the lack of availability of an easily applied reproducible stain that can highlight the grain pathology with sensitivity and with minimal background. The Gallyas silver iodide technique is not widely used and, even in experienced hands, is difficult to perform due to inconsistencies inherent in silver-based techniques on thin sections. Grain pathology can be detected using immunohistochemistry for phosphorylated tau protein, but the grain pathology is most often masked by background tau-positive material; leading to problems with interpretation, especially for practitioners seeing small numbers of cases. There is a need for a reliable immunohistochemical stain that can detect grain pathology and provide a clear contrast between grains and other tau-positive neurodegenerative pathologies. We have investigated the novel ubiquitin-binding protein p62 as a potential biomarker for grain pathology in argyrophilic grain disease. Four cases of argyrophilic grain disease, in which the pathology was determined using the Gallyas silver iodide technique, were re-assessed using paraffin-embedded sections immunostained with antibodies specific for p62. We found that the detection of grain pathology was more sensitive than with silver-based techniques and that the resolution of the pathology was significantly improved. We suggest that p62 could be used to replace the Gallyas technique in the routine diagnosis of argyrophilic grain disease.  相似文献   
7.
Frontotemporal dementia (FTD) is a clinically heterogeneous disorder characterized by alterations in language and/or behavior, often in association with Parkinsonism or motor neuron disease. A familial form of FTD is associated with mutations in the microtubule-associated protein tau (MAPT) gene. We report here on the clinical, neuroimaging, cerebral spinal fluid biomarker, genetic, biochemical and postmortem neuropathological analyses of a case of familial FTD with a Leu266Val MAPT mutation which results in a very early age of onset and a rapid course of disease. This is also the first reported case of any MAPT mutation in an individual of African American ethnicity. Grant Acknowledgement: The research reported here was supported by grants AG17586, AG10124, NS44266, K08 NS14108, and K08 AG20073 from the National Institutes on Aging and Neurological Disorders and Stroke of the National Institutes of Health, Department of Health and Human Services.  相似文献   
8.
The progressive development of Alzheimer disease (AD)-related lesions, such as neurofibrillary tangles (NFT), amyloid deposits and synaptic loss, and the occurrence of microvascular and small macrovascular pathology within the cerebral cortex are conspicuous neuropathologic features of brain aging. Recent neuropathologic studies strongly suggested that the clinical diagnosis of dementia depends more on the severity and topography of pathological changes than on the presence of a qualitative marker. However, several methodological problems, such as selection biases, case–control design, density-based measures and masking effects, of concomitant pathologies persisted. In recent years, we performed several clinicopathologic studies using stereological counting of AD lesions. In order to define the cognitive impact of lacunes and microvascular lesions, we also analyzed pure vascular cases without substantial AD pathology. Our data revealed that total NFT numbers in the CA1 field, cortical microinfarcts and subcortical gray matter lacunes were the stronger determinants of dementia. In contrast, the contribution of periventricular and subcortical white matter demyelinations had a modest cognitive effect even in rare cases with isolated microvascular pathology. Importantly, in cases with pure AD pathology, more than 50% of Clinical Dementia Rating scale variability was not explained by NFT, amyloid deposits and neuronal loss in the hippocampal formation. In cases with microvascular pathology or lacunes, this percentage was even lower. The present review summarizes our data in this field and discusses their relevance within the theoretical framework of the functional neuropathology of brain aging and with particular reference to the current efforts to develop standardized neuropathological criteria for mixed dementia.  相似文献   
9.
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been identified in families with autosomal dominant late-onset Parkinson disease (PD). Lrrk2 is a phylogenetically conserved, ubiquitous protein, which is constitutively expressed in various cells including neurons and glial cells of human brain. We recently reported that Lrrk2 is identified in Lewy bodies in PD as well as in neuronal and glial inclusions in several other neurodegenerative disorders. Here we show that Lrrk2 is closely associated with the tau-positive inclusions in eight members of a family with frontotemporal dementia of the pallido-ponto-nigral degeneration type linked to the chromosome 17 N279K tau mutation (N279K/FTDP-17/PPND). Lrrk2 is colocalized with tau in oligodendroglial coiled bodies and intracytoplasmic neuronal inclusions. HLA-DR positive reactive microglia and ICAM-1 positive reactive astrocytes accumulated in affected areas demonstrating that inflammatory processes are also involved in the disease pathogenesis. Western blot analysis of soluble extracts of N279K/FTDP-17/PPND brain tissue suggests that C-terminal fragment(s) of apparent 64–75 kDa molecular weight may be the major Lrrk2 species in pathological deposits. The possibility that Lrrk2 is linked with various neurodegenerative disorders through the ubiquitin proteosome pathway is discussed. The results indicate that Lrrk2 is linked to frontotemporal atrophy of PPND type caused by N279K tau mutation. They also show that chronic inflammation is involved in the pathogenesis of N279K/FTDP-17/PPND.  相似文献   
10.
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