bluuebunny/crossref_metadata_2025 huggingface dataset:
Semantic Dysfunction in Frontotemporal Lobar Degeneration
Authors: Snowden Julie S.
Published: April 2003

Semantic dementia, characterized by loss of word meaning and impaired face and object recognition, is one of the clinical manifestations of frontotemporal lobar degeneration and is associated with atrophy of the inferior and middle temporal gyri. Patients may present predominantly with problems in naming and understanding words, or in face and object recognition, the verbal or nonverbal predominance reflecting the accent of atrophy on the left or right temporal lobe. Behavioural changes may occur, although these have a more obsessional quality than is typically seen in frontotemporal dementia (FTD). However, overlap in clinical symptomatology of semantic dementia and FTD may occur with disease progression reinforcing the link between these clinical syndromes. Semantic dysfunction is poorly recognized and may be mistaken for the amnesia of Alzheimer’s disease, yet may be important in explaining some of the behavioural characteristics seen in focal cerebral degeneration.
Behavioral Symptomatology and Care of Patients with Frontotemporal Lobe Degeneration – Based on the Aspects of the Phylogenetic and Ontogenetic Processes
Authors: Tanabe Hirotaka , Ikeda Manabu , Komori Kenjiro
Published: April 2003

The behavioral changes of patients with frontotemporal lobe degeneration are studied from the aspects of the phylogenetic and ontogenetic processes of the brain. It is proposed that some behavioral changes could be utilized for the patients’ care.
Synapse Density Related to Cerebral Blood Flow and Symptomatology in Frontal Lobe Degeneration and Alzheimer’s Disease
Authors: Liu Xiaoying , Passant Ulla , Risberg Jarl , Warkentin Siegbert , Brun Arne
Published: April 2003

In order to evaluate the functional significance of synaptic pathology, synaptic density was quantitated and related to clinical symptomatology and regional cerebral blood flow (rCBF) in 8 patients with frontal lobe degeneration of non-Alzheimer type (FLD) and 19 patients with Alzheimer’s disease (AD). Synaptic density was measured in all layers of prefrontal and parietal cortex. The clinical picture of FLD was dominated by a frontal lobe syndrome with changes in personality and behavior, while AD was dominated by temporoparietal symptoms. This parallels the finding of frontal rCBF reductions in FLD patients and temporoparietal reductions in AD patients. Synaptic density was significantly decreased in both FLD and AD, with a regional severity which closely correlated with that of the degeneration, symptomatology and rCBF deficit. The results suggest that synaptic pathology is a likely cause of clinical symptoms and regional metabolic decrement in dementia.
Tau Mutations in Frontotemporal Dementia
Authors: Wilhelmsen Kirk C. , Clark Lorraine N. , Miller Bruce L. , Geschwind Daniel H.
Published: April 2003

Genetic analysis has determined that a series of disorders related clinically and pathologically to frontotemporal dementia (FTD) are etiologically related. The relationship between these disorders was initially established based on linkage analysis and has been solidified by the identification of mutations in the tau gene in many families. Mutations affecting the expression or structure of the microtubule binding domain of the tau gene have been found in many large families with chromosome 17q21–22-linked disease. These mutations only account for a small fraction of cases of FTD that are either sporadic or that contain only a few affected relatives.
Galantamine: Therapeutic Effects beyond Cognition
Authors: Blesa Rafael
Published: April 2003

Decline in cognitive function, especially memory, is the core feature of Alzheimer’s disease (AD). However, other characteristic aspects of the disease are also important. These include patients’ activities of daily living (ADL), including quality of sleep, behavioural disturbances and the impact of the disease on the caregiver. Therefore, increasing attention is being paid to clinically meaningful outcome measures, such as the Disability Assessment for Dementia (DAD) scale, the Neuropsychiatric Inventory (NPI), caregiver time and the Pittsburgh Sleep Quality Index (PSQI). Galantamine is a new treatment for AD that combines modulation of nicotinic receptors with inhibition of acetylcholinesterase. The present review outlines the positive and sustained effects of this agent on patients’ behaviour and daily functioning as well as on caregiver time. In studies of up to 5 months’ duration, galantamine-treated patients had a significantly better outcome on ADL than placebo-treated patients, and after 12 months of treatment with galantamine, patients’ functional ability was preserved. Galantamine also significantly benefits behavioural disturbances in patients with AD. These functional and behavioural benefits are associated with a decrease in the burden on caregivers, as indicated by a reduction, relative to placebo, in the time spent supervising and assisting patients. These clinical benefits are not offset by disruption of patients’ sleep, as has been reported with other cholinergic treatments.
Neuritogenic-Neurotoxic Effects of Membrane-Associated Forms ofAmyloid Precursor Prot ein
Authors: Neill David , Hughes David , Leake Alan , Morris Christopher , Jones Debbie , Oakley Arthur , Edwardson James , Estibeiro Petra
Published: April 2003

The membrane-bound glycoprotein, amyloid precursor protein (APP), plays a central role in Alzheimer’s disease (AD). The present paper investigates the neuritogenic-neurotoxic properties of this protein and relates them to possible aetiopathological mechanisms in AD. Marked differences in neuritic differentiation were detected when comparing untransfected tetraploid mouse neuroblastoma cells (or vector only cells) with transfected cells overexpressing APP751. Transfected cells developed neurites quicker, and whereas all transfected cells differentiated, the degree of differentiation of untransfected cells was more variable. Fully differentiated transfected and untransfected cells had marked differences in neuritic morphology. Transfected cells had more neurites per cell, these being shorter and more branched than neurites on untransfected cells. The precocious differentiation of transfected cells was not maintained with neuritic process disintegration and cell death occurring from the seventh day onwards. Untransfected cells continued to extend their neuritic processes for up to five weeks. Membrane-associated forms of APP were responsible for these effects, rather than secreted APP or the β/A4-peptide. Combined data from Western blot and immunocytochemical procedures showed a prominent accumulation of APP-C-terminal fragments in the perinuclear region, neuritic varicosities and growth cones of transfected cells, suggesting their involvement in the neuritogenic-neurotoxic process. Similar neuritogenic-neurotoxic mechanisms occurring in vivo, in association with compensatory synaptoplastic responses in the aged brain, may be part of the pathological process in AD.
High Expression of Apolipoprotein E mRNA in the Brains with Sporadic Alzheimer’s Disease
Authors: Yamagata Kaoru , Urakami Katsuya , Ikeda Kazuyuki , Ji Yong , Adachi Yoshiki , Arai Hiroyuki , Sasaki Hidetada , Sato Kenzo , Nakashima Kenji
Published: April 2003

In order to study progressive dementia in Alzheimer’s disease (AD) patients, we analyzed the gene expression of apolipoprotein E (apoE). ApoE mRNA level in the brains of patients with AD was determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. ApoE genotype and the promoter polymorphisms (–491A/T, Th1/E47cs) were determined by the PCR restriction fragment length polymorphism method. The apoE mRNA level was significantly higher in the AD group than the control group (p < 0.05). ApoE mRNA in the AD group with apoE Ε4 was also significantly higher than that in the control group with apoE Ε4 (p < 0.05). Our result did not indicate the possibility that the promoter polymorphisms modulate the apoE mRNA level. The higher level of apoE mRNA in AD with apoE Ε4 may play an important role in the development of AD.
Age-Related Changes in Energy Production in Fresh Senescence-Accelerated Mouse Brain Slices as Revealed by Positron Autoradiography
Authors: Omata Naoto , Murata Tetsuhito , Fujibayashi Yasuhisa , Waki Atsuo , Sadato Norihiro , Yoshimoto Mitsuyoshi , Wada Yuji , Yonekura Yoshiharu
Published: April 2003

To investigate age-related changes in cerebral energy production, we compared senescence-accelerated prone mice (SAMP8) as an animal model of accelerated aging and senescence-accelerated resistant mice (SAMR1) as a control. Considering that the cerebral glucose metabolic rate (CMRglc) at the time of O2 deprivation and 2,4-dinitrophenol (DNP) loading would reflect anaerobic glycolytic capacity and mitochondrial function, respectively, we investigated dynamic changes in CMRglc before and after loading with these perturbations. Fresh brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36°C, and serial two-dimensional time-resolved images of [18F]FDG uptake in these slices were obtained on the imaging plates. The fractional rate constant (=k3*) of [18F]FDG proportional to the CMRglc was evaluated by applying the Gjedde-Patlak graphical method to the image data. The k3* value before the hypoxic perturbation in all of the brain sites analyzed was higher in SAMP8 than SAMR1 in both the 2- and 10-month-old groups. With O2 deprivation, k3* values were higher without site specificity in the 2-month-old SAMP8 than in 2-month-old SAMR1, whereas in 10-month-old mice, there was no significant difference between the two groups. In contrast, with DNP loading, while no significant difference was noted between 2-month-old SAMP8 and 2-month-old SAMR1, in 10-month-old mice, the SAMP8 group showed lower values in certain regions than SAMR1 mice. These results suggest that in the brain tissue of SAMP8, a marked transient enhancement of anaerobic glycolytic capacity in the 2-month-olds and a decrease in mitochondrial function in the subsequent period occur, as a result of which glucose metabolism appears to be enhanced in both the 2- and 10-month-old groups compared to SAMR1 mice.
Regional Cerebral Blood Flow and Prognostic Evaluation in Alzheimer’s Disease
Authors: Nobili Flavio , Copello Francesco , Buffoni Ferdinando , Vitali Paolo , Girtler Nicola , Bordoni Chiara , Safaie-Semnani Elham , Mariani Giuliano , Rodriguez Guido
Published: April 2003

The present investigation reports the application of regional cerebral blood flow (rCBF; 133Xe method) to prognostic purposes in a consecutive series of 76 patients (mean age 68.4 ± 8.7 years) with probable Alzheimer’s disease (AD; NINCDS-ADRDA criteria). The likelihood that rCBF from a posterior temporal-inferior parietal area in each hemisphere at the first visit may predict timing of achievement of three endpoints (i.e. loss of activity of daily living, ADL, incontinence and death due to end-stage AD) was tested by the ‘lifereg’ procedure of the Statistical Analysis System package. With respect to baseline evaluation, 32 patients lost ADL 20.6 ± 17.4 months later, 31 developed incontinence 27.1 ± 19.0 months later, and 16 patients died after 40.9 ± 23.8 months of follow-up. Baseline rCBF significantly predicted all end-points: the loss of ADL (left hemisphere: p = 0.04; righth hemisphere: p = 0.02), incontinence (p = 0.02 in both hemispheres) and death (p = 0.01 in both hemispheres). Statistical significance was maintained for the loss of ADL and incontinence both in a subgroup of mildly demented patients, in whom death was not considered due to the low number of patients who died, and in a multivariate analysis including patient age, age at onset, sex, duration of illness, Mini-Mental State Examination score and presence of extrapyramidal signs and psychotic symptoms at the first visit. This study shows that rCBF measurement in a posterior temporal-inferior parietal area may give prognostic information on timing of evolution of AD, whenever performed during the course of the disease, and may be utilized both in clinical practice and for social planning.
Cerebrospinal Fluid Tau Levels Increase with Age in Healthy Individuals
Authors: Blomberg Mari , Jensen Malene , Basun Hans , Lannfelt Lars , Wahlund Lars-Olof
Published: April 2003

Cerebrospinal fluid (CSF) tau is a promising biochemical ante-mortem marker for Alzheimer’s disease (AD). Levels are increased in AD compared to other dementias, neurological diseases and healthy controls. An age-related decrease in both soluble tau and tau bound to paired helical filaments has been shown in brains from non-demented subjects. To study tau levels in normal ageing, we investigated CSF in 29 healthy individuals aged 45–80 years. A statistically significant increase in CSF tau with increasing age was found which might be caused by neuronal loss during normal ageing and redistribution of soluble tau from the brain into CSF. We could not demonstrate any influence by the APOE genotype, though larger populations have to be investigated to confirm this result. In conclusion, we found an age-dependent increase in CSF tau in healthy individuals. We emphasise the importance of establishing an age-dependent interval of CSF tau in non-demented subjects.
Analogues, Ageing and Aberrant Assimilation of Vitamin B12 in Alzheimer’s Disease
Authors: McCaddon Andrew , Hudson Peter , Abrahamsson Lars , Olofsson Hasse , Regland Björn
Published: April 2003

Vitamin B12 assimilation might be disrupted in patients with Alzheimer’s disease. We therefore measured B12 carrier protein saturation and inactive B12 ‘analogues’ in patients compared with healthy elderly individuals in a prospective case-controlled survey. Twenty-three patients, aged 60 or over, with features compatible with DSM-IV criteria for primary degenerative dementia of the Alzheimer type were recruited together with 18 cognitively intact age-matched control subjects. Total vitamin B12 (active corrinoids), holo- and apo-haptocorrin and transcobalamin were measured in serum. B12 analogues (inactive corrinoids) were estimated from the difference between R-binder-determined corrinoids and an intrinsic factor based B12 assay. Alzheimer patients had significantly lower active corrinoid than control subjects and the analogue/corrinoid ratio was significantly higher in the Alzheimer group. The inter-relationship between age, analogues and transcobalamin polarised patients into two distinct groups. Two disparate mechanisms might exist for the development of cerebral B12 deficiency in Alzheimer’s disease, although both imply a disruption of selective B12 assimilation and analogue elimination in such patients.
Elevated Serum Total and LDL Cholesterol in Very Old Patients with Alzheimer’s Disease
Authors: Lesser G. , Kandiah K. , Libow L.S. , Likourezos A. , Breuer B. , Marin D. , Mohs R. , Haroutunian V. , Neufeld R.
Published: April 2003

The relationships of serum lipids with Alzheimer’s disease (AD) and other dementias in very old patients are not clear. All residents of an academic nursing home were studied clinically for dementia and for serum lipids. All those autopsied over a 7.7-year period had apolipoprotein E (apoE) genotyping and detailed neuropathological examination. Those with pathologically defined criteria for AD (n = 84) were compared to all others who also had clinical dementia but did not show AD changes (n = 22). In contrast to most other reports of serum lipids in very old patients with AD, total cholesterol (TC) and low density lipoprotein cholesterol levels were each significantly higher for those with AD. The lipid-AD associations were progressively stronger with increasing pathological certainty of AD diagnosis. These relationships remained significant after adjustment for apoE genotype and for other known risk factors. The lipid-AD associations in a very old cohort, and prior evidence that elevated TC in middle life is a risk factor for later dementia, prompt consideration of factors associated with lipid metabolism in the development of Alzheimer’s dementia.
Utility of 99mTc-HM-PAO SPECT Hippocampal Image to Diagnose Early Stages of Alzheimer’s Disease Using Semiquantitative Analysis
Authors: Nebu Akihiko , Ikeda Manabu , Fukuhara Ryuji , Komori Kenjiro , Maki Naruhiko , Hokoishi Kazuhiko , Shigenobu Kazue , Kikuchi Takanori , Tanabe Hirotaka
Published: April 2003

Objective: Examination of the utility of 99mTc-hexamethylpropylene amine oxide (99mTc-HM-PAO) SPECT hippocampal image to diagnose early stages of Alzheimer’s disease (AD) using semiquantitative analysis. Subjects: 10 early-stage AD patients and 8 normal sex-matched elderly controls. Setting: Outpatient division of the Ehime University Hospital. Method: We performed 99mTc-HM-PAO SPECT perfusion imaging in each subject. A semiquantitative method of assessing regional variation was used. The regions of interest for temporal regions were set at images parallel to the long axis of the hippocampal formation which were reconstructed at 30Results: The regional cerebral blood flow ratio of the bilateral medial temporal lobe at the hippocampal image was significantly lower in the AD subjects than in the normally aged controls without any other differences in ordinary transaxial images. Conclusion: This study suggests that 99mTc-HM-PAO SPECT hippocampal images might be a helpful tool for the diagnosis of very-early-stage AD.
Circulating Leptin Levels and Weight Loss in Alzheimer’s Disease Patients
Authors: Power Dermot A. , Noel Jacques , Collins Ronan , O’Neill Des
Published: April 2003

Weight loss is common in Alzheimer’s disease (AD) and is predictive of mortality. Leptin, an adipocyte-derived peptide hormone is implicated in the regulation of satiety and energy expenditure. It acts on the hypothalamus to suppress appetite and increase energy expenditure. We undertook this study to determine if inappropriately elevated leptin levels play a role in AD-associated weight loss. Serum leptin levels of 8 patients in each of the following groups were determined: (1) AD, body mass index (BMI) >25; (2) AD, BMI <20; (3) non-Alzheimer’s (vascular) dementia (VaD), BMI >25, and (4) VaD, BMI <20. Mean serum leptin levels were significantly lower in below-appropriate-weight patients (both AD and VaD) than in appropriate-weight controls. Below-appropriate-weight AD patients had a significantly lower mean serum leptin concentration than appropriate-weight VaD controls. Weight loss is a feature of AD. Inappropriately elevated leptin levels do not appear to be implicated. Indeed, we have shown that the afferent limb of the leptin feedback loop is intact in below-appropriate-weight AD patients and suggest hypothalamic dysfunction may underlie this feature.
Occipital Glucose Metabolism in Dementia with Lewy Bodies with and without Parkinsonism: A Study Using Positron Emission Tomography
Authors: Imamura Toru , Ishii Kazunari , Hirono Nobutsugu , Hashimoto Mamoru , Tanimukai Satoshi , Kazui Hiroaki , Hanihara Tokiji , Sasaki Masahiro , Mori Etsuro
Published: April 2003

Reduction of glucose metabolism in the occipital lobe is reported in dementia with Lewy bodies (DLB) and Parkinson’s disease. If dysfunction of the nigrostriatal system is responsible for occipital hypometabolism, (1) DLB patients with parkinsonism would show a lower occipital metabolism than do patients without parkinsonism, and (2) DLB patients without parkinsonism would show an occipital metabolism comparable to those of normal subjects and patients with Alzheimer’s disease (AD). To examine these hypotheses, we studied the regional cerebral metabolic rate of glucose (rCMRglc) in patients with a clinical diagnosis of DLB or AD, using 18F-fluorodeoxyglucose and positron emission tomography. The subjects consisted of 15 DLB patients with parkinsonism, 7 DLB patients without parkinsonism and 7 AD patients without parkinsonism. The medial and lateral occipital rCMRglc was significantly lower in the DLB patients without parkinsonism than in the AD patients. There were no significant differences in occipital metabolic rates between the DLB groups with and without parkinsonism. DLB patients without parkinsonism showed a significant reduction of occipital glucose metabolism which is comparable with that of DLB patients with parkinsonism. The neurobiological bases of occipital hypometabolism in DLB may be pathological processes in the brainstem or basal forebrain structures other than the nigrostriatal system.
Synaptosomal Proteins, Beta-Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein (Beta-SNAP), Gamma-SNAP and Synaptotagmin I in Brain of Patients with Down Syndrome and Alzheimer’s Disease
Authors: Yoo Byong Chul , Cairns Nigel , Fountoulakis Michael , Lubec Gert
Published: April 2003

Although it is well-known that synaptosomal proteins are deranged in neurodegenerative disorders, no information is available at the protein-chemical level as mainly immunochemical or immunohistochemical data were reported previously. We therefore investigated synaptosomal proteins in brain specimens from patients with Down syndrome (DS) and Alzheimer’s disease (AD) to challenge the DS synaptic pathology as well as the relevance of DS to AD in synaptic pathology. For the aim of this study, we employed two-dimensional electrophoresis and matrix-associated laser desorption ionization mass spectroscopy and determined β-soluble N-ethylmaleimide-sensitive factor attachment protein (β-SNAP), γ-SNAP and synaptotagmin I (SYT I) in 7 individual brain regions of controls and patients with DS and AD. In DS brain, β-SNAP was significantly reduced in temporal cortex (p < 0.01). SYT I (p65) and SYT I (pI 7.0) were significantly reduced in thalamus (p < 0.01 and p < 0.05, respectively). In AD brain, β-SNAP was significantly decreased in temporal cortex (p < 0.05). SYT I (p65) was significantly reduced in cerebellum (p < 0.05), and temporal (p < 0.001) and parietal cortex (p < 0.01). SYT I (pI 7.0) was significantly reduced in temporal (p < 0.001) and parietal cortex (p < 0.01) and thalamus (p < 0.01). γ-SNAP did not show any change in both DS and AD. The findings may explain impaired synaptogenesis in DS and AD brain, which is well documented in DS brain already early in life, and/or synaptosomal loss secondary to neuronal loss observed in both neurodegenerative disorders. It may also represent, reflect or account for the impaired neuronal transmission in DS and AD, caused by deterioration of the exocytic machinery. Here, we provide evidence for several deranged synaptosomal proteins in several brain regions at the protein level indicating deficient synaptosomal wiring of the brain in DS and AD.
Chronic Donepezil Treatment Is Associated with Slowed Cognitive Decline in Alzheimer’s Disease
Authors: Doody R.S. , Dunn J.K. , Clark C.M. , Farlow M. , Foster N.L. , Liao T. , Gonzales N. , Lai E. , Massman P.
Published: April 2003

Objective: To compare rates of cognitive decline between probable Alzheimer’s disease (AD) patients treated with long-duration cholinesterase inhibitors (ChE-Is) and those who remained untreated. Background: ChE-Is, including donepezil and tracrine, have shown beneficial effects on cognition and global functioning in patients with AD. The duration of these benefits is unknown because the longest double-blind placebo-controlled studies reported were only approximately 6 months long. Ethical concerns regarding randomization of patients to placebo for long periods make it difficult to undertake trials of longer duration. Methods: We identified patients in 4 AD centers who were or were not consistently treated with ChE-Is and who had demographic, psychometric and follow-up data. We compared 205 ChE-I-treated and 218 untreated AD patients on baseline variables hypothesized to differ between these groups, on baseline Mini Mental Status Examination (MMSE) scores and on rates of MMSE change at 1 year. The analysis was performed initially with all ChE-I-treated patients as a single group versus untreated subjects, and then with donepezil versus untreated subjects and tacrine versus untreated subjects. Results: As expected, treated and untreated patients differed with respect to age, education, ethnicity, percentage of community dwelling and exact days of follow-up (ANOVA and χ2) in several comparisons, but did not differ on baseline MMSE score. These baseline variables were highly intercorrelated. MMSE scores declined significantly more slowly after 1 year of ChE-I treatment compared to untreated patients (p = 0.05) after controlling for baseline differences in age, education, ethnicity and percentage of community dwelling. Slowing of decline was significant in the donepezil-treated patients (p = 0.007) but not in the tacrine-treated group (p = 0.33). Conclusions: This study, utilizing concurrent, nonrandomized controls, suggests that donepezil continues to have efficacy over at least the first year of therapy. Other studies are needed to determine whether the benefits are maintained beyond 1 year.
Relationship between Blood Flow Kinetics and Severity of Alzheimer’s Disease: Assessment of Severity Using a Questionnaire-Type Examination, Alzheimer’s Disease Assessment Scale, Cognitive Sub-Scale (ADAScog)
Authors: Nebu Akihiko , Ikeda Manabu , Fukuhara Ryuji , Shigenobu Kazue , Maki Naruhiko , Hokoishi Kazuhiko , Komori Kenjiro , Yasuoka Takuo , Tanabe Hirotaka
Published: April 2003

We assessed hemokinetics associated with changes in Alzheimer’s disease (AD) severity in 90 AD patients by researching the relationship between AD Assessment Scale, cognitive sub-scale (ADAScog) scores and regional cerebral blood flow (rCBF). In the present study, we employed the questionnaire-type ADAScog examination to accurately assess the severity of AD. Between five groups classified on the basis of ADAScog score, significant differences were observed in parietal, lateral temporal and superior frontal rCBF. In addition, in parietal and lateral temporal regions, significant correlations were also observed between ADAScog score and rCBF. In superior frontal rCBF, significant differences were noted only between group 5 (≥40 ADAScog points) and each of the other groups; there was no significant correlation between rCBF and ADAScog score. Thus, we propose the following mechanism for blood flow kinetics associated with changed severity: In an early stage of AD, blood flow in the medial temporal cortex is impaired, and gradually involves the temporoparietal regions. While the medial temporal impairment of blood flow reaches a plateau, temporoparietal blood flow continues to be impaired well into a severe stage, at which point blood flow impairment in the frontal region is initiated.
The Bayer-Activities of Daily Living Scale (B-ADL): Results from a Validation Study in Three European Countries
Authors: Erzigkeit Hellmut , Lehfeld Hartmut , Peña-Casanova Jordi , Bieber Florian , Yekrangi-Hartmann Chirin , Rupp Markus , Rappard F. , Arnold Klaus , Hindmarch Ian
Published: April 2003

The Bayer-Activities of Daily Living Scale (B-ADL) is a 25-item, informant-rated questionnaire which was developed as a brief and internationally applicable instrument for assessing functional disabilities. The scale’s target group are elderly patients suffering from mild to moderate dementia or cognitive impairment. To investigate the reliability and validity of different language versions, the B-ADL was administered in the UK, Germany, and Spain to a total of 1,433 subjects with a wide range of cognitive decline. The results from the three country samples were very similar, with internal consistency being above 0.98 (Cronbach alpha). A factor analysis revealed that a one-factor solution accounted for most of the variance. The B-ADL total score significantly increased between adjacent Global Deterioration Scale (GDS) stages 1 to 5. A second factor analysis entering additional variables (GDS stage, Mini-Mental State Examination or MMSE subscores, age, years of education, gender, and country) revealed that all B-ADL items loaded on the same factor, ‘dementia severity’, and that they were not related to age, education, gender, or country. In the identification of subjects with clinically manifest dementia symptoms (GDS stages 4 and 5), the B-ADL proved to be as efficient as the MMSE in the UK and German samples and superior to the MMSE in the Spanish sample.
Normal Optic Nerve Head Topography in the Early Stages of Dementia of the Alzheimer Type
Authors: Kergoat Hélène , Kergoat Marie-Jeanne , Justino Lisette , Robillard Alain , Bergman Howard , Chertkow Howard
Published: April 2003

In view of the existing controversy as to whether or not the optic nerve head (ONH) is altered in Alzheimer disease, we used modern imaging technology to evaluate the ONH structure in individuals with dementia of the Alzheimer type (DAT). Real-time topographical images of the ONH were obtained with a Heidelberg retina tomograph from individuals in the early stages of DAT and age-matched controls. The various ONH parameters examined in this study did not differ significantly between DAT and age-matched subjects. These results suggest that the deficits in visual function that are known to occur in DAT are not related to ONH structural anomalies, at least in the earlier stages of the disease.
The Swedish APP670/671 Alzheimer’s Disease Mutation: The First Evidence for Strikingly Increased Oxidative Injury in the Temporal Inferior Cortex
Authors: Bogdanovic Nenad , Zilmer Mihkel , Zilmer Kersti , Rehema Aune , Karelson Ello
Published: April 2003

To evaluate the level of oxidative stress (OS) in familial Alzheimer’s disease (FAD), we analysed four cerebrocortical areas from patients with Swedish FAD bearing the APP670/671 mutation. The temporal inferior cortex (TIC) from Swedish FAD patients revealed a striking 2- to 3-fold increase in diene conjugates, lipid peroxides and protein carbonyls, compared to sporadic Alzheimer’s disease (AD). Compared with TIC from sporadic AD patients, the mutation carriers showed a markedly decreased activity of catalase (CAT) in the same area, and the same trend was found for another antioxidant enzyme, superoxide dismutase. These results are consistent with the deep oxidative injury of TIC in Swedish FAD. In the frontal inferior cortex (FIC), sensory postcentral cortex (SPCC) and occipital primary cortex (OPC) from Swedish FAD, the parameters of oxidative injury tended to be higher than in sporadic AD. Only the increase in the levels of lipid hydroperoxides in SPCC and of protein carbonyls in OPC was significant. Compared to sporadic AD, Swedish FAD showed a significant increase in GSSG levels and the GSSG/2GSH ratio in the FIC, SPCC and OPC. A significantly decreased activity of CAT was detectable for the SPCC and OPC in Swedish FAD. Increased OS might play a crucial role in the rapid progression of Swedish FAD from the associative temporal cortex to the primary cerebrocortical areas.
Primary Degenerative Mild Cognitive Impairment: Study Population, Clinical, Brain Imaging and Biochemical Findings
Authors: Lautenschlager Nicola T. , Riemenschneider Matthias , Drzezga Alexander , Kurz Alexander F.
Published: April 2003

Mild cognitive impairment (MCI) is a heterogeneous clinical syndrome for which no international diagnostic criteria have yet been established. Longitudinal studies have shown that many individuals who later develop dementia pass through a stage of MCI. We are following up 36 individuals who were initially diagnosed as having the memory-impaired primary degenerative type of MCI and therefore are at high risk of developing Alzheimer’s disease. Clinical, neuropsychological, brain imaging and CSF biochemical markers were examined. Findings were remarkably heterogeneous even in this highly selected group of patients. This suggests that MCI is aetiologically not uniform.
Frontotemporal Lobar Degeneration: A Study in Japan
Authors: Hokoishi Kazuhiko , Ikeda Manabu , Maki Naruhiko , Nebu Akihiko , Shigenobu Kazue , Fukuhara Ryuji , Komori Kenjiro , Tanabe Hirotaka
Published: April 2003

Frontotemporal lobar degeneration is the most common form of cortical dementia occurring in the presenium after Alzheimer’s disease. We analyzed two types of frontotemporal dementia (FTD) and semantic dementia (SD) selected from a consecutive series of outpatients based on neuropsychological symptoms, psychiatric symptoms and abnormal behavior. In our series of 134 patients with primary degenerative dementia, there were 16 cases of FTD and 6 cases of SD. Patients with subgroups of FTD and patients with SD were distinguishable only by the presence of aphasia in the latter group. They were not distinguishable from one another by other neuropsychological examinations, behavioral abnormalities or psychiatric symptoms assessed with the Neuropsychiatric Inventory.
Repeated Pain Assessment in Alzheimer’s Disease
Authors: Scherder Erik , Bouma Anke , Slaets Joris , Ooms Marcel , Ribbe Miel , Blok Astrid , Sergeant Joseph
Published: April 2003

In previous studies, patients with probable Alzheimer’s disease (AD) have indicated that they experienced less pain intensity and affect from their painful conditions than nondemented elderly persons. However, in those studies, pain assessment occurred only once. Therefore, it may be possible that pain which had occurred, for example, a day earlier, could have been forgotten. Therefore, in the present study, AD patients’ pain was assessed daily, i.e. once a day and even three times a day, during a longer period. The results parallel those of earlier studies, i.e. compared to elderly persons without dementia, AD patients appear to perceive less pain intensity and pain affect. These findings support the hypothesis that AD is characterized by an alteration in pain experience.
Efficacy of Topical 0.05% Retinaldehyde in Skin Aging by Ultrasound and Rheological Techniques
Authors: Diridollou S. , Vienne M.-P. , Alibert M. , Aquilina C. , Briant A. , Dahan S. , Denis P. , Launais B. , Turlier V. , Dupuy P.
Published: April 2003

Background: The natural precursor of retinoic acid, i.e. retinaldehyde, has been proven to exert retinoid activities. Aim and Methods: The aim of this prospective instrument study was to determine the effect of topical retinaldehyde 0.05% on the physical properties of aging skin. This was performed using two devices, namely a high-resolution (70–80 µm) ultrasound scanner, which visualizes the thickness of both the epidermis and the dermis, and an echorheometer, which assesses the stiffness and elasticity of the skin by suction. In a 1-year study, 21 patients applied retinaldehyde cream 0.05% on the face, while another group of 19 volunteers were only treated with an emollient (control group). Epidermal and dermal thicknesses were measured on the forehead and temple, and stiffness and elasticity were measured on the forehead only. All the instrumental parameters were assessed at baseline and at the end of treatment. Results: Compared to the control group, retinaldehyde treatment induced a significant increase in epidermal thickness of the temple, as well as in cutaneous elasticity (p < 0.01). Similarly, retinaldehyde treatment tended to increase dermal thickness and reduce cutaneous stiffness, but no statistical difference could be observed between the two groups. Conclusion: Taken together, the results further suggest that retinaldehyde has counteracting effects on skin aging
Stability and Biological Activity of Epoietin Beta in Parenteral Nutrition Solutions
Authors: Huynh-Delerme C. , Penaud J.-F. , Lacombe C. , Brunhes A. , Moriette G.
Published: April 2003

The aim of this in vitro study was to determine stability and biological activity of epoietin (Epo) beta in a parenteral nutrition solution over 24 h. Epo beta was added to the parenteral nutrition solution which was administered through intravenous tubing and a Posidyne Neo filter. Samples were collected after 0, 4, 12, and 24 h. The Epo concentrations were measured before and after filter passage by an ELISA assay. The Epo biological activity was determined in the UT7/Epo cell line. The Epo concentration in the parenteral nutrition solution remained stable for 24 h. However, 35% of the Epo was adsorbed by the filter. The samples collected induced proliferation of UT7/Epo cells. These results suggest that Epo can be administered in parenteral nutrition solutions, but the dosage would need to be increased when a filter is used.
Prophylactic Administration of Porcine-Derived Lung Surfactant Is a Significant Factor in Reducing the Odds for Peri-Intraventricular Haemorrhage in Premature Infants
Authors: Walti Hervé , Paris-Llado Josefa , Egberts Johannes , Brand Roland , Bevilacqua Giulio , Gardini Fabrizio , Bréart Gérard
Published: April 2003

We hypothesized that prophylactic treatment with a porcine-modified lung surfactant (PLS) reduces the rate of peri-intraventricular haemorrhage (PIVH) more than rescue treatment. We performed a meta-analysis of three prophylactic versus rescue trials conducted with PLS in four countries using individual data. Overall (grades 1–4) or severe (grades 3 and 4) PIVH of 671 newborns was the outcome. A logistic regression analysis was performed. Prophylactic exposure to PLS was a significant independent factor in reducing the incidence of overall (OR 0.65; 95% CI 0.47–0.90) and severe (OR 0.56; 95% CI 0.35–0.89) PIVH. Moreover, for severe PIVH, the adjusted OR for outborn babies exposed to prophylactic treatment with PLS was highly significant (OR 0.11; 95% CI 0.02–to 0.49). The results we obtained show that prophylactic treatment with PLS reduces the rate of PIVH more than rescue treatment.
Neuroendocrine and Immune Responses to Acute Endotoxemia in Suckling and Weaned Piglets
Authors: Kanitz Ellen , Tuchscherer Margret , Tuchscherer Armin , Stabenow Bernd , Manteuffel Gerhard
Published: April 2003

The objective of this study was to characterize effects of weaning stress on behavioural, endocrine and immune responses to acute peripheral lipopolysaccharide (LPS) challenge in neonatal pigs. Weaning in 28-day-old piglets was accompanied by a significant increase in ACTH concentrations (p = 0.0378) and an increase in basal cortisol level (p = 0.0135). There was also a significant suppressive effect on lymphocyte proliferation in response to concanavalin A (p = 0.0048) in newly weaned piglets. Peripheral administration of LPS induced vomiting, diarrhoea and somnolence in both suckling and weaned piglets. The frequency of these signs of sickness was significantly higher in weaned piglets compared with suckling piglets (p = 0.0049). Additionally, LPS significantly increased plasma concentrations of TNF-α, cortisol and ACTH. While weaned piglets reacted to LPS with a higher release of ACTH (p = 0.0239) and cortisol (p = 0.0015) than suckling piglets there was no significant effect of weaning on the magnitude of TNF-α. The present data indicate that weaning suppresses the lymphocyte function, causes changes in endocrine regulation and has a substantial effect on the behavioural and endocrine response to an acute peripheral LPS challenge; consequently it could increase disease susceptibility.
Neonatal Intestinal Occlusion due to Duodenal Duplication in Association with Malformed Gallbladder Sludge
Authors: Messina Mario , Ferrucci Elisabetta , Meucci Daniela , Buonocore Giuseppe , Di Maggio Giovanni
Published: April 2003

Duodenal duplications are rare observations which can be diagnosed during early pregnancy via US scan. In the neonate they are often cause for intestinal occlusions. Surgical treatment can be limited by the duplication’s anatomical interrelationships with adjacent organs. Biliary sludge is an uncommon finding in the first year of life, and can readily regress spontaneously. The association between duodenal duplication and sludge has never been described in the literature in the neonatal period. Here, for the first time, we report on the case of a newborn infant with cystic duplication of the duodenum associated with sludge in a misshapen gallbladder.
UV Transmission Measurements of Small Skin Specimens with Special Quartz Cuvettes
Authors: Hoffmann K. , Kaspar K. , Altmeyer P. , Gambichler T.
Published: April 2003

Background: The penetration of different wavelengths of UV radiation through human skin is of major importance, especially for the determination of photoprotective properties of sunscreens and UV-protective clothes. Objective: In this study we present a new method for the measurement of UV transmission through small skin specimens. Methods: The transmission measurements were performed by using a UV spectrophotometer with an integrating sphere operating in the wavelength range of 280–390 nm. For the skin samples, special quartz glass cuvettes were developed which allowed measurements for very thin and small skin specimens. Furthermore, the cuvettes prevented dehydration of the specimens and guaranteed, by using an additional diaphragm, that the transmission data were derived solely from the small skin specimen examined. Specimens measuring 8 × 3 mm2 with a thickness of 0.3 mm (histometric and sonographic control) were taken from the thighs of 10 subjects via shave biopsy. Results: In the UVA range (315–390 nm) we obtained a mean transmission of 4.6% and for the UVB range (280–315 nm) of 0.9%. No significant (p >0.14) difference of UV transmission was found between the individual skin specimens. Conclusion: This new method seems to be well suitable for UV transmission measurements of small skin specimens. As UVA radiation has a much deeper penetration depth and in in vivo situations dermal hemoglobin could have an effect on UV penetration, the present method is better suitable for the investigation of UVB-induced biological adaptation mechanisms and the impact of topical agents on UVB transmission of the epidermis.
Topical Metronidazole in Seborrheic Dermatitis – A Double-Blind Study
Authors: Parsad Davinder , Pandhi Roma , Negi K.S. , Kumar Bhushan
Published: April 2003

Objective: To evaluate the role of topical metronidazole gel in the treatment of seborrheic dermatitis. Methods: Forty-four patients with seborrheic dermatitis were enrolled in the study. All topical treatments were stopped for at least 2 weeks before the patients were allocated at random to receive either metronidazole 1% gel or placebo for 8 weeks. The severity score was measured at the initial evaluation, and the patients were followed up at 2-week intervals for 8 weeks. A global evaluation of improvement was done at 8 weeks. Results: Thirty-eight patients completed the study; 21 patients in the metronidazole group and 17 patients in the placebo group could be evaluated. There was a statistically significant decrease of the mean score even at week 2; the difference became highly significant at 8 weeks (p < 0.001). On the final evaluation at 8 weeks, 14 patients in the metronidazole group showed marked improvement to complete clearance as compared to only 2 patients having moderate improvement in the placebo group (p < 0.001). Conclusion: The present trial has demonstrated the effectiveness of topical 1% metronidazole gel in seborrheic dermatitis.
Quality of Life of Greek Patients with Inflammatory Bowel Disease
Authors: Pallis A.G. , Vlachonikolis I.G. , Mouzas I.A.
Published: April 2003

Background/Aims: Health-related quality of life (HRQOL) is an important outcome measure in inflammatory bowel disease (IBD). The aim of our study is to validate the Greek translation of the Inflammatory Bowel Disease Questionnaire (IBDQ). For this we assessed its construct validity, discriminant ability, reliability and sensitivity to change. Methods: One hundred and fourteen patients with IBD (69 UC, 45 CD) completed the Greek version of the IBDQ, and a Visual Analogue Scale (VAS) for general well-being. Fifty-two patients also completed the SF-36. A subgroup of 46 patients completed the Greek IBDQ for a second time. Clinical activity was assessed by Harvey-Bradshaw Index and Colitis Activity Index. Results: Correlation coefficients between the four dimensional scores of the Greek IBDQ and the clinical activity indexes, VAS and the SF-36 were all reasonably high and statistically significant. The Greek IBDQ was able to discriminate well between groups of patients with either different clinical disease activity or subjective assessment of well-being. It also showed high reliability when it was repeated in patients who reported no change in their general well-being (intraclass correlation coefficient 0.940–0.998). In contrast, there was a significant difference between the baseline and the follow-up measurement in patients who reported change in their general well-being. Conclusions: The Greek IBDQ proved to be a valid and reliable instrument for assessing HRQOL, useful in the evaluation of clinical trials or health surveys as well as in the therapeutic management of IBD patients.
Long-Term Results of Stapled and Hand-Sewn Anastomoses in Patients with Crohn’s Disease
Authors: Ikeuchi Hiroki , Kusunoki Masato , Yamamura Takehira
Published: April 2003

Aim: This study aimed at determining the reoperation rates of patients with anastomoses for Crohn’s disease. The outcome of patients undergoing stapled anastomoses was compared with that of patients having hand-sewn anastomoses. Methods: Sixty-three patients undergoing intestinal resection for Crohn’s disease at our institution from 1987 to 1996 were studied in a prospective, randomized trial. The group undergoing stapling comprised 30 patients and 37 anastomoses. The group with a hand-sewn anastomosis comprised 33 patients and 45 anastomoses. The median follow-up period was 87 (range 36–140) months. Results: There were no significant differences in operative indications or patients’ age and sex between the groups. There was a significant difference in cumulative recurrences between the groups (Cox-Mantel test: p = 0.022). Conclusion: A stapled anastomosis after resection for Crohn’s disease may delay reoperation in patients with symptomatic recurrence.
Reoperative Surgery for Postcholecystectomy Bile Duct Injuries
Authors: Chaudhary Adarsh , Chandra Abhijit , Negi Sanjay S. , Sachdev Ajay
Published: April 2003

Background: Surgical repair for a postcholecystectomy bile duct injury can be complicated by the development of an anastomotic stricture which necessitates re-intervention. The authors reviewed their experience with patients requiring re-operation after unsuccessful surgical repair of the bile duct injury, to analyze the possible causes of the failure of the operative procedure and the long-term outcome following revisional surgery. Methods: Retrospective analysis of the records of 41 patients referred to a tertiary care center for the management of recurrent stricture following surgical repair performed for a postcholecystectomy bile duct injury. Results: Before referral, 69 operative procedures had been performed on these 41 patients. Factors likely to be associated with increased chances of failure of the biliary reconstructive procedures included presentation with cholangitis after the biliary injury, no cholangiographic study before the surgical repair and surgical intervention within 3 weeks of the injury. Thirty-seven (90%) patients were found to have strictures at or above the level of confluence of right and left hepatic ducts, while at the time of the index repair only 12 (29%) patients had an injury at that level. Revisional surgery in all the patients was a Roux-en-Y hepaticojejunostomy. One patient died, 2 patients with multiple previous operations developed recurrence and needed intervention again. Over a mean follow-up period of 4.2 years, 90% patients had a satisfactory outcome. Conclusion: Development of recurrent stricture following surgical repair of a postcholecystectomy biliary injury can be related to the technique and timing of the surgical procedure, the complication may therefore be avoidable in some patients. In experienced hands the results of revisional surgery are good but are adversely affected as the number of previous repairs increases.