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1.
Meeus B Verstraeten A Crosiers D Engelborghs S Van den Broeck M Mattheijssens M Peeters K Corsmit E Elinck E Pickut B Vandenberghe R Cras P De Deyn PP Van Broeckhoven C Theuns J 《Neurobiology of aging》2012,33(3):629-629.e18
Based on the substantial overlap in clinical and pathological characteristics of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) with Alzheimer disease (AD) and Parkinson disease (PD) we hypothesized that these disorders might share underlying genetic factors. The contribution of both sequence and copy number variants (CNVs) in known AD and PD genes to the genetic etiology of DLB and PDD however is currently unclear. Therefore, we performed a gene-based mutation analysis of all major AD and PD genes in 99 DLB and 75 PDD patients, including familial and sporadic forms, from Flanders, Belgium. Also, copy number variants in APP, SNCA, and PARK2 were determined. In the AD genes we detected proven pathogenic missense mutations in PSEN1 and PSEN2, and 2 novel missense variants in PSEN2 and MAPT. In the PD genes we identified 1 SNCA duplication, the LRRK2 R1441C founder mutation and 4 novel heterozygous missense variants with unknown pathogenicity. Our results suggest a contribution of established AD and PD genes to the genetic etiology of DLB and PDD though to a limited extent. They do support the hypothesis of a genetic overlap between members of the Lewy body disease spectrum, but additional genes still have to exist. 相似文献
2.
《Neurobiology of aging》2014,35(12):2836-2844
The loss of zinc transporter 3 (ZnT3) has been implicated in age-related cognitive decline in mice, and the protein has been associated with plaques. We investigated the levels of ZnT3 and postsynaptic density protein 95 (PSD95), a marker of the postsynaptic terminal, in people with Parkinson's disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer's disease (AD, n = 16), and controls (n = 24), using semiquantitative western blotting and immunohistochemistry in 3 cortical regions. Standardized cognitive assessments during life and semiquantitative scoring of amyloid β (Aβ), tau, and α-synuclein at postmortem were used to investigate the relationship between ZnT3 and PSD95, cognition and pathology. Associations were observed between ZnT3 and PSD95 levels in prefrontal cortex and cognitive impairment (p = 0.001 and p = 0.002, respectively) and between ZnT3 levels in the parietal cortex and cognitive impairment (p = 0.036). Associations were also seen between ZnT3 levels in cingulate cortex and severity of Aβ (p = 0.003) and tau (p = 0.011) pathologies. DLB and PDD were characterized by significant reductions of PSD95 (p < 0.05) and ZnT3 (p < 0.001) in prefrontal cortex compared with controls and AD. PSD95 levels in the parietal cortex were found to be decreased in AD cases compared with controls (p = 0.02) and PDD (p = 0.005). This study has identified Zn2+ modulation as a possible novel target for the treatment of cognitive impairment in DLB and PDD and the potential for synaptic proteins to be used as a biomarker for the differentiation of DLB and PDD from AD. 相似文献
3.
Dementia and visual hallucinations are common complications of Parkinson's disease (PD), yet their patho-anatomical bases are poorly defined. We studied α-synuclein (αSyn), tau and amyloid-β (Aβ) pathology in the claustrum of 20 PD cases without dementia, 12 PD cases with dementia (PDD) and 7 cases with dementia with Lewy bodies (DLB). αSyn positivity was observed in 75% of PD cases without dementia and in 100% of PDD and DLB cases. Aβ was observed in the claustrum in 25% of PD, 58% of PDD and 100% of DLB cases. Tau was negligible in all cases restricting further analysis. Compared to PD cases without dementia, PDD cases demonstrated a significantly greater αSyn burden in the claustrum (p = 0.0003). In addition, DLB cases showed a significantly increased αSyn deposition when compared to PDD (p = 0.02) and PD without dementia (p = 0.0002). A similar hierarchy, PD < PDD < DLB was seen in terms of Aβ burden in the claustrum. Comparison of αSyn and Aβ burden in those cases with and without visual hallucinations did not reveal any significant associations (p = 0.13 and 0.1, respectively). We demonstrate that pathology in the claustrum, a region of largely obscure physiological function, strongly relates to the presence of dementia in Parkinson's disease and DLB. 相似文献
4.
Positron emission tomography (PET) studies have demonstrated reduced acetylcholine esterase (AChE) activity as an indicator of cholinergic impairment, which is a main pathogenic process in Alzheimer's disease (AD). The E4 allele of apolipoprotein ? (ApoE4) is a major risk factor for AD. We examined the relation between ApoE-genotype and cortical AChE activity. In 19 patients (mean age 64) with mild to moderate AD (mean MMSE 22) PET with C-11-labeled N-methyl-4-piperidyl-acetate (MP4A) was performed and the ApoE4-genotype was determined. Parametric images of AChE hydrolysis were generated using a non-invasive technique and analysed globally and regionally. A neuropsychological battery testing memory, attention, executive functions, visuoconstruction, and language was administered. The mean cortical AChE activity was reduced significantly in both groups compared to reference values. The ApoE4 positive subjects (two homozygotes, nine heterozygotes) had significantly higher (p < 0.05) AChE levels (MP4A hydrolysis rate 0.0753 ± 0.0088 min−1) than the ApoE4 negative subjects (n = 8, 0.0654 ± 0.0090 min−1). Both groups were comparable with regard to age (63 versus 65) and dementia severity (MMSE 20 versus MMSE 22). AChE-impairment correlated significantly with the word fluency task (r = 0.041, p < 0.05) in the ApoE4 negative group only. These results indicate that cortical AChE activity is relatively well preserved in ApoE4 carriers, either by preservation of its cellular expression or as AChE activity in amyloid plaques. 相似文献
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6.
Cardiac meta-iodobenzylguanidine (MIBG) uptake on 123I-MIBG cardiac scintigraphy is reduced in patients with Lewy body disease such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure, and has been reported to be useful for differentiating PD from other parkinsonian syndromes, as well as DLB from Alzheimer disease (AD). Postmortem studies have shown that the number of tyrosine hydroxylase (TH)-immunoreactive nerve fibers of the heart was decreased in pathologically-confirmed Lewy body disease, supporting the findings of reduced cardiac MIBG uptake in Lewy body diseases. Now, reduced cardiac MIBG uptake can be a potential biomarker for the presence of Lewy bodies in the nervous system. 123I-MIBG cardiac scintigraphy can allow us to determine the presence of Lewy bodies. 相似文献
7.
Objective
The PREPARE programme study is a randomized controlled trial which aims to determine whether structured education can be used to increase physical activity and improve glucose tolerance in individuals with impaired glucose tolerance (IGT). This paper outlines the rationale, design and baseline data from the PREPARE programme study.Methods
Individuals with IGT were recruited from ongoing diabetes screening programmes. Outcomes included an oral glucose tolerance test, physical activity (piezoelectric pedometer) and psychological determinants.Results
103 individuals (male n = 65; female n = 38) were recruited, 28% of whom were from a South Asian ethnic background. At baseline the participants’ mean age and BMI were 64 ± 9 years and 29.4 ± 4.5 kg/m2 respectively. Steps per day were associated with 2-h glucose (ρ = −0.22, p = 0.03), fasting glucose (ρ = −0.22, p = 0.04), HDL-cholesterol (ρ = 0.23, p = 0.02), triglycerides (ρ = −0.22, p = 0.03) and body fat percentage (ρ = −0.26, p = 0.01). Mean self-efficacy scores were significantly (p < 0.01) higher for walking than for any other form of exercise. Participants reported high levels of concern about their IGT status but were confident that exercise would help treat/control IGT.Conclusion
This study demonstrates the importance of developing effective physical activity and self-management programmes for individuals with IGT.Practice implications
This study provides a detailed framework for the promotion of physical activity in a population identified with an increased risk of developing type 2 diabetes which, if successful, could feasibly be implemented in a primary health care or community setting. 相似文献8.
Ka Kit Wong Martijn L.T.M. Muller Hiroto Kuwabara Stephanie A. Studenski Nicolaas I. Bohnen 《Neuroscience letters》2010
Olfactory dysfunction may precede common neurodegenerative disorders in the elderly, such as Alzheimer (AD) or Parkinson disease (PD). However, pathobiological mechanisms of olfactory loss in the elderly are poorly understood. Although nigrostriatal dopaminergic denervation is a key patholobiological feature of PD, age-associated nigrostriatal denervation (AASDD) occurs also with normal aging and can be more prominent in some elderly. We investigated the relationship between AASDD and olfactory performance in community-dwelling subjects. Community-dwelling subjects (n = 73, 44 F/29 M, mean age 64.0 ± 16.4, range 20–85) underwent brain dopamine transporter (DAT) [11C]2-β-carbomethoxy-3β-(4-fluorophenyl) tropane (β-CFT) positron emission tomography (PET) imaging and olfactory assessment using the 40-odor University of Pennsylvania Smell Identification Test (UPSIT). Subjects with clinical or DAT PET evidence of Parkinson disease (PD) were not eligible for the study. AASDD was defined based on normative data in young and middle-aged subjects. Compared to a mild and general linear decline in odor identification observed in most subjects (R2 = 0.18, P = 0.0002), there were 13 subjects who deviated below the 5% confidence interval level in age-predicted UPSIT scores. Analysis limited to elderly subjects 60 years and over demonstrated a significant association between poor smell (n = 10 out of 49, 20.4%) and AASDD (χ2 = 4.4, P < 0.05). There is a significant association between olfactory dysfunction and more prominent nigrostriatal denervation in the elderly. Olfactory assessment may have potential as a screening tool to detect age-accelerated neurodegeneration in the elderly. 相似文献
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10.
Shino Magaki Ravi Raghavan Claudius Mueller Kerby C. Oberg Harry V. Vinters Wolff M. Kirsch 《Neuroscience letters》2007
Accumulating evidence implicates a role for altered iron and copper metabolism in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, imbalances in the levels of the various forms of iron at different stages of AD have not been examined. In this pilot study we extracted and measured the levels of loosely bound, non-heme and total iron and copper in the frontal cortex and hippocampus of patients with mild–moderate AD (n = 3), severe AD (n = 8) and dementia with Lewy bodies (DLB, n = 6), using graphite furnace atomic absorption spectrometry (GFAAS). Additionally, the expression of iron regulatory protein 2 (IRP2) was examined in relation to the pathological hallmarks of AD and DLB, amyloid plaques, neurofibrillary tangles (NFT), and Lewy bodies, by immunohistochemistry. We found significantly decreased loosely bound iron in the hippocampal white matter of mild–moderate and severe AD patients and a trend towards increased non-heme iron in the hippocampal gray matter of severe AD patients. Furthermore, decreased levels of total copper were seen in severe AD and DLB frontal cortex compared to controls, suggesting an imbalance in brain metal levels in both AD and DLB. The decrease in loosely bound iron in mild–moderate AD patients may be associated with myelin breakdown seen in the beginning stages of AD and implicates that iron dysregulation is an early event in AD pathogenesis. 相似文献
11.
Patel A Rees SD Kelly MA Bain SC Barnett AH Thalitaya D Prasher VP 《Neuroscience letters》2011,487(2):144-148
Background: Down syndrome (DS) is caused by either complete or partial triplication of chromosome 21, affecting approximately 1/1000 live births, and it is widely accepted that individuals with DS are more likely to develop dementia of Alzheimer's disease (DAD) compared with the general population. Many studies have investigated genetic susceptibility to AD in the general population, resulting in a number of potential candidate genes that may influence the development of DAD. The majority of these variants, however, have not been investigated in subjects with DS. Aim: The aim of this study was to determine whether genetic variants previously associated with AD in the general population, were also associated with DAD in individuals with DS. Methods: Genotyping of 43 SNPs within 28 genes was undertaken in 187 individuals with Down syndrome with and without dementia of Alzheimer's disease, using the SNPlex platform. Results: Significant associations of SNPs in five genes with DAD in DS were found, namely APOE, SORL1, BACE1, RUNX1 and ALDH18A1. As expected, the most strongly associated SNP was the APOE ?4 rs429358 variant (HR = 2.47 [1.58, 3.87], p = 7.52 × 10−5), although variants within the more recently implicated SORL1 and RUNX1 genes were also strongly associated with DAD in DS (HR = 0.54 [0.37, 0.80], p = 0.002 and HR = 1.61 [1.15, 2.26], p = 0.006 respectively). Conclusions: Our study demonstrates that a number of variants previously associated with AD in the general population are also associated with DAD in DS. To enable us to determine whether these variants, as well as other more recently revealed AD susceptibility variants, truly contribute to the development of DAD in DS, further multi-centre collaborative studies comprising large number of individuals with DS are needed. 相似文献
12.
Masaaki Waragai Masaaki Nakai Jianshe Wei Masayo Fujita Hideya Mizuno Gilbert Ho Eliezer Masliah Hiroyasu Akatsu Fusako Yokochi Makoto Hashimoto 《Neuroscience letters》2007
DJ-1 is a multifunctional protein whose loss of function by gene mutations may play a causative role for familial Parkinson's disease (PD). A recent study has shown that the expression of this molecule is upregulated in both brains and cerebrospinal fluids (CSF) in various neurological disorders, including sporadic PD, Alzheimer's disease (AD) and stroke, raising a possibility that DJ-1 could be a potential biomarker for these diseases. In this context, the main objective of the present study was to determine if DJ-1 was increased in the plasma of PD patients. For this purpose, blood plasma samples collected from sporadic PD patients, dementia with Lewy bodies (DLB) and healthy age-matched controls were analyzed by immunoblotting and enzyme-linked immunosorbent assay. The results showed that the plasma DJ-1 levels in PD (n = 104) were higher than those in control (n = 80) (p < 0.05). Moreover, the plasma DJ-1 levels in the advanced stage of PD (n = 52, Yahr III–IV) were higher than those in the early stage of PD (n = 52, Yahr I–II) (p < 0.05), demonstrating that the plasma DJ-1 was correlated with the disease severity in PD. Plasma DJ-1 levels were also significantly higher in DLB (n = 30) compared with both controls and early stage of PD (p < 0.01). Taken together, these results suggest that the plasma DJ-1 could be a useful biomarker for the evaluation of the disease severity in PD and possibly in other Lewy body diseases. 相似文献
13.
Yoshiki Hase Tuomo M. Polvikoski Michael J. Firbank Lucinda J. L. Craggs Emily Hawthorne Charlotte Platten William Stevenson Vincent Deramecourt Clive Ballard Rose Anne Kenny Robert H. Perry Paul Ince Roxana O. Carare Louise M. Allan Karen Horsburgh Raj N. Kalaria 《Brain pathology (Zurich, Switzerland)》2020,30(1):191-202
We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD‐DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α‐synuclein pathology. We found moderate‐severe vascular changes and high‐vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub‐set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α‐synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging‐related neurodegenerative disorders and characterize their end‐stage clinical syndromes. 相似文献
14.
Objective
The aim of the study was to confirm the superior efficacy of estriol containing pessaries compared to placebo in the treatment of vaginal atrophy.Study design
In a prospective, multicenter, randomized, placebo-controlled, double-blind study, 436 postmenopausal women with vaginal atrophy (vaginal maturation index, VMI < 40%; vaginal pH > 5; most bothersome symptom, MBS ≥ 65 on visual analogue scale, VAS) were treated with pessaries containing either 0.2 mg estriol (N = 142) or 0.03 mg estriol (N = 147) or with a matching placebo (N = 147) for 12 weeks.Main outcome measures
Primary efficacy endpoints included increase in VMI, decrease of the vaginal pH value and decrease in intensity of MBS after 12 weeks of treatment.Results
The increase in VMI was significantly greater under 0.2 mg estriol and 0.03 mg estriol (46.3 ± 17.0 and 38.4 ± 19.4, respectively) compared to placebo (23.9 ± 21.5; p values < 0.001), vaginal pH decreased significantly more (−1.6 ± 0.8 and −1.4 ± 0.9, respectively) compared to placebo (−0.6 ± 0.8; p values < 0.001) and MBS intensity (VAS) declined significantly more (−52.2 ± 23.7 and −47.1 ± 23.4, respectively) compared to placebo (−31.8 ± 26.3; p values < 0.001). Adverse events were rare and occurred at similar rates in all three groups.Conclusions
Superiority of estriol containing pessaries over placebo was shown in the local treatment of vaginal atrophy. Even a very low dose of 0.03 mg estriol proved sufficient for local treatment of vaginal atrophy with excellent tolerability. 相似文献15.
Yuanzhe Li Takeshi Sekine Manabu Funayama Lin Li Hiroyo Yoshino Kenya Nishioka Hiroyuki Tomiyama Nobutaka Hattori 《Neurobiology of aging》2014
The glucocerebrosidase gene (GBA) is a known risk factor of Parkinson's disease (PD). We sequenced entire coding exons and exon/intron boundaries of GBA in 147 Japanese familial PD (FPD) patients from 144 families and 100 unrelated control subjects. Twenty-seven of 144 (18.8%) of index patients were heterozygous for known Gaucher disease mutations, suggesting that GBA heterozygous mutations are strongly associated with FPD (odds ratio = 22.9, 95% confidence interval = 3.1–171.2). The frequency was significantly higher in autosomal dominant PD (ADPD) compared with autosomal recessive PD. According to clinical assessments, PD patients with GBA mutations exhibited typical manifestations of PD or dementia with Lewy bodies (DLB), such as L-dopa responsive parkinsonism with psychiatric problems and/or cognitive decline. Interestingly, they also presented with reduced myocardial 123I-metaiodobenzylguanidine uptake. Our findings suggest that heterozygous GBA mutations are strong risk factors in FPD, especially for autosomal dominant PD. Some patients with GBA heterozygous mutations develop clinical features of DLB. We speculate that GBA dysfunction may promote Lewy body formation, resulting in more severe PD or DLB phenotypes that are inherited in families. 相似文献
16.
Wright-Nunes JA Luther JM Ikizler TA Cavanaugh KL 《Patient education and counseling》2012,88(2):184-188
Objective
To describe patient hypertension knowledge and associations with blood pressure measurements.Methods
Patients with chronic kidney disease (CKD) were asked about the impact of high blood pressure on kidneys and their target blood pressure goal. Systolic blood pressure was measured using automated sphygmomanometers.Results
In 338 adults with hypertension and pre-dialysis CKD, the median [IQR] age was 59 [47,68] years, 45% [n = 152] were women, and 18% [n = 62] were non-white. Lower systolic blood pressure (SBP) was associated with female sex (SBP mmHg median [IQR] 132 [117,149] women vs. 137 [124,152] men; p = 0.04), less advanced CKD (SBP 134 [122,147] stages 1–2 vs. 132 [118,148] stage 3 vs. 140 [125,156] stages 4–5; p = 0.01), and patient ability to correctly identify SBP goal (SBP 134 [119,150] correct vs. 141 [125,154] incorrect; p = 0.05). In adjusted analysis, knowledge of blood pressure goal remained independently associated with lower SBP (−9.96 mmHg [−19.97, −1.95] in correct respondents vs. incorrect; p < 0.001).Conclusion
Patient knowledge of goal blood pressure is independently associated with improved blood pressure control.Practice implications
Interventions to improve patient knowledge of specific blood pressure targets may have an important role in optimizing blood pressure management. 相似文献17.
Background
Low levels of cardiorespiratory fitness have proven to be associated with a higher risk of premature death from all causes, specifically from cardiovascular disease. However, there has been no study conducted to describe the cardiorespiratory fitness normative values in Chinese midlife and elderly.Objectives
To provide normative values of cardiorespiratory fitness expressed as maximal oxygen uptake (VO2max) and its association with body composition and physical activity in Chinese midlife and elderly women in Hong Kong.Methods
659 Chinese women aged from 55 to 94 years were recruited from two existing cohorts: the carotid atherosclerosis in women Hong Kong cohort study and the Osteoporotic Fractures in Women (MsOS) Hong Kong cohort study. Symptom-limited maximal exercise testing on an electrically braked bicycle ergometer was performed to assess VO2max, where the subject was connected to a calibrated metabolic cart for gas analysis. Their body composition and physical activity data were also assessed.Results
The body mass index was 23.4 kg/m2 and the mean fat mass and lean body mass were 16.6 kg and 37.3 kg, respectively. The mean VO2max was 20.3 ± 4.1 ml/kg/min (range, 7.9–35.7 ml/kg/min). VO2max decreased with age, with the rate of decline 0.25 ml/kg/min/yr (7.1% per decade). In a subgroup of 475 women from the MsOS study, the decline in VO2max was found to depend on ageing (β = 0.31, P < 0.001), body mass index (β = −0.30, P < 0.001) and levels of physical activity (β = 0.02, P < 0.001). Fat mass was also independently associated with VO2max (β = −0.20, P < 0.001).Conclusions
This study describes the normative values of VO2max in a sample of Chinese midlife and elderly women which provides a valuable reference to assess health and fitness in Chinese elderly. Results from this study also suggested that body composition and levels of physical activity were important determinants of the age-related decline in VO2max. 相似文献18.
Pupillary response test using dilute phenylephrine, a sympathetic agonist, and dilute pilocarpine, a cholinergic agonist, were performed in 24 patients with dementia with Lewy bodies (DLB), 40 patients with Alzheimer's disease (AD), and 23 normal elderly subjects. The mydriatic response to 0.5% phenylephrine was significantly greater in the DLB group than in the AD and control groups. The mydriatic change correlated inversely with the reduction in cardiac 123I-metaiodobenzylguanidine uptake. In contrast, miotic response to 0.0625% pilocarpine was significantly greater in the DLB and AD groups than in the control group. The pupil assay using combined phenylephrine and pilocarpine eye drop test may be useful in the detection of patients with DLB and AD and in distinguishing between them. 相似文献
19.
Dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) are characterized by loss of acetylcholine (ACh) from cortical areas. Clinical studies report positive effects of acetylcholine esterase (AChE) inhibitors in PDD and dementia with Lewy bodies. We here report that the number of neurons expressing a cholinergic marker in the medial septum-diagonal band of Broca complex decreases in A30P α-synuclein-expressing mice during aging, paralleled by a lower AChE fiber density in the dentate gyrus and in the hippocampal CA1 field. After inducing dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), no acute but a delayed loss of cholinergic neurons and AChE-positive fibers was observed, which was attenuated by L-3,4-dihydroxyphenylalanine (DOPA) treatment. Expression of nerve growth factor (NGF) and tyrosine receptor kinase A (TrkA) genes was upregulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride-treated wild type mice, but not in A30P α-synuclein expressing animals. In contrast, upregulation of sortilin and p75NTR genes was found in the A30P α-synuclein-expressing mice. These results suggest that dopamine deficiency may contribute to the impairment of the septohippocampal system in patients with PDD and that L-3,4-dihydroxyphenylalanine may not only result in symptomatic treatment of the akinetic-rigid syndrome but may also alleviate the degeneration of basal forebrain cholinergic system and the cognitive decline. 相似文献
20.
Lehto SM Tolmunen T Kuikka J Valkonen-Korhonen M Joensuu M Saarinen PI Vanninen R Ahola P Tiihonen J Lehtonen J 《Neuroscience letters》2008,441(3):291-295
Data on neurobiological differences between major depression (MD) and double depression (DD) are scarce. We examined the striatum dopamine (DAT) and midbrain serotonin transporter (SERT) binding of [123I] nor-β-CIT in DD patients (n = 8) and compared it to that in MD patients (n = 11) and healthy controls (n = 19). Drug-naïve patients and controls were imaged by single-photon emission computed tomography at baseline, and the patients also after one year of psychodynamic psychotherapy. Both DD and MD groups had lower midbrain [123I] nor-β-CIT binding compared with the controls. Baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores significantly decreased in both groups after one year of psychotherapy (DD: t = 3.55, p = 0.009; MD: t = 5.86, p < 0.001). No differences between the DD and MD groups were observed in age-adjusted baseline striatum or midbrain [123I] nor-β-CIT binding or its change during psychotherapy. Age-adjusted baseline striatum [123I] nor-β-CIT binding correlated inversely with the duration of both dysthymia (rho = −0.76, p = 0.03) and MD (rho = −0.83, p = 0.01) in the DD group. No such finding was observed in the MD group (rho = 0.26, p = 0.44). Baseline HAM-D-17 did not correlate with the change in striatum or midbrain [123I] nor-β-CIT binding in either group. In conclusion, our findings suggest that when using midbrain [123I] nor-β-CIT binding as a marker of SERT binding, no differences are detectable between patients with DD and MD. However, low striatum [123I] nor-β-CIT binding, a marker of DAT binding, may be associated with a longer illness duration in dysthymia. 相似文献