bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrolytic Treatment of Colorectal Liver Tumour Deposits in a Rat Model: A Technique with Potential for Patients with Unresectable Liver Tumours
Authors: Wemyss-Holden Simon A. , Robertson Gavin S.M. , de la M. Hall Pauline , Dennison Ashley R. , Maddern Guy J.
Published: April 2003

Background/Aims: Patients with unresectable malignant liver tumours have a poor prognosis. A technique is needed which improves long-term survival. Previous studies in the rat have shown that electrolysis is a safe, predictable and reproducible method for creating areas of necrosis in the normal rat liver. This study examined the effects of electrolysis on colorectal liver ‘metastases’ in the rat. Methods: Tumours of colorectal origin were implanted into the livers of Wistar-WAG rats. Two weeks after implantation the tumours were treated with electrolysis. A direct current generator, connected to 2 platinum intrahepatic electrodes was used to examine the effects of various electrode configurations on the extent of tumour necrosis. Results: Significant (p<0.001) tumour ablation was achieved with all electrode configurations. Tumour necrosis was more complete (p<0.05) with the electrodes positioned on either side of the tumour than with both electrodes placed in the centre of the tumour. Liver enzymes (AST and ALT) were significantly (p<0.001) elevated after treatment, but returned towards normal by 2 days. Conclusions: This study has shown that colorectal liver ‘metastasis’ can be ablated by electrolysis in a rat model. Two separate mechanisms of tumour ablation were observed: With the electrodes directly in or adjacent to the tumour, necrosis resulted from the action of cytotoxic electrode products, whereas by positioning the electrodes proximal to the tumour, necrosis was induced by a ‘secondary’ ischaemic effect. The findings confirm the view that electrolysis has great potential for treating patients with unresectable malignant liver tumours.
Dementia and Borna Disease Virus
Authors: Igata Tomohide , Yamaguchi Kazunari , Igata-Yi Ruriko , Yoshiki Keiko , Takemoto Shigeki , Yamasaki Hiroshi , Matuoka Masao , Miyakawa Taihei
Published: April 2003

Human Borna disease virus (BDV) infection has been reported to be a threat to mental health [1]. BDV is an unclassified, nonsegmented negative sense single-stranded RNA virus which naturally infects horses, cattle, cats and sheep [2, 3]. Infection causes disturbances in behavior and cognitive function [1]. Recently, seroepidemiological and molecular evidence of BDV infection has been found in humans with psychiatric disorders [4, 5], although healthy people also have a low prevalence of BDV genome and anti-BDV antibodies [6, 7]. Patients with dementia also have disturbed behavior and cognitive function. For the first time, we investigated the relationship between dementia and BDV infections.
Benton’s Visual Retention Test in Patients with Polycystic Lipomembranous Dysplasia with Sclerosing Leukoencephalopathy
Authors: Hakola H.P.A.
Published: April 2003

Eighteen patients suffering from polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy were examined with Benton’s Visual Retention Test (BVRT, form C, administration A). Both the scoring system for correct reproductions (CR) and that for specific errors (SE) were used. The stage of patients’ dementia was also diagnosed with a neuropsychiatric follow-up study. The impairment of the patients’ results in BVRT correlated with the severity of their dementia. There were high correlation coefficients between the stage of clinical dementia and the differences in CR and SE.
Possible Roles of Transglutaminases in Alzheimer’s Disease
Authors: Yamada T. , Yoshiyama Y. , Kawaguchi N. , Ichinose A. , Iwaki T. , Hirose S. , Jefferies W.A.
Published: April 2003

The localizations of two transglutaminases [factor XIIIa and tissue transglutaminase (tTG)] and their mRNAs were examined in human brain tissues from neurologically normal and Alzheimer disease (AD) cases, using immunohistochemical and in situ hybridization methods. In all cases, meningeal macrophages and ependymal macrophage/microglia were positive for factor XIIIa. The mRNA encoding factor XIIIa was detected in macrophages and microglia. As reported previously, intense staining with the antibody to factor XIIIa of a subset of microglia was seen in the parietal cortex in AD brains. Few or no microglia were found associated with classical senile plaques. In contrast, many labeled microglia were associated with primitive plaques. Furthermore, most of these cells were mainly seen in the subpial cortical layer but were very rare in the hippocampus. On the other hand, few factor-XIIIa-positive microglia were found in the parietal cortices from non-neurological cases, but moderate numbers were found in their hippocampal tissues. TG and its mRNA were localized in astrocytes in all the cases. In AD, a few neurofibrillary tangles were positive to tTG. These results suggest that the subsets of microglia which express factor XIIIa may play some roles in the early phase of AD pathology.
Factors Affecting the Utilization of Homecare Supports by Caregiving Relatives of Alzheimer Patients
Authors: Vetter P. , Steiner O. , Kraus S. , Moises H. , Kropp P. , Möller W.-D. , Köller O.
Published: April 2003

Thirty-six homecare patients with dementia of Alzheimer type (DAT) and their caregiving relatives were studied to determine the factors influencing their use or nonuse of available medical, institutional, instrumental, and legal supports. The rate of utilization of homecare support was found to be surprisingly low. Only when the burden of providing care had become intolerable did relatives resort to homecare support (homecare allowance, counseling, outpatient services, etc.). The main reason for the low utilization was poor knowledge regarding the availability of homecare supports. Since all of the DAT patients were under the care of a family doctor, this information deficit could best be overcome by improved counseling from personal physicians.
Apolipoprotein E Genotype in Sporadic Early- and Late-Onset Alzheimer’s Disease
Authors: Masullo C. , Daniele A. , Seripa D. , Filippini V. , Gravina C. , Carbone G. , Gainotti G. , Fazio V.M.
Published: April 2003

The σ4 isoform of apolipoprotein E (ApoE) has been proposed as a risk factor for Alzheimer’s disease (AD), while the possible role of the σ2 allele in AD is controversial. We have studied the ApoE genotype in 38 patients with early-onset AD (EOAD) and in 43 patients with late-onset AD (LOAD). In the EOAD group we observed a significant increase of σ4 allele frequency as compared with normal controls, while there was a more than 3-fold decrease of σ2 allele frequency that did not reach statistical significance. In the LOAD group we found a highly significant increase of σ4 allele frequency as compared with normal controls, while there was a significant decrease of σ2 allele frequency. In both the EOAD and LOAD groups, no significant difference was observed between σ4 carriers and σ4 noncarriers as for age at disease onset, disease duration, and Mini-Mental State score at observation. However, in both EOAD and LOAD groups a statistical trend towards a longer disease duration was observed in σ4 carriers. In both the EOAD and LOAD groups, disease severity was compared in σ4 carriers versus σ4 noncarriers by means of analyses of covariance, with disease duration as covariate. No significant difference between σ4 carriers and σ4 noncarriers was observed in both EOAD and LOAD. The results of the present study confirm that σ4 allele seems to be associated with an increased risk for sporadic AD, while the significant decrease of σ2 allele frequency in the LOAD group supports the hypothesis of a possible protective role of σ2 allele in AD.
Lack of Association between an Intronic Polymorphism in the Presenilin-1 Gene and Sporadic Late-Onset Alzheimer Disease in Polish Patients
Authors: Kowalska Anna , Wender Mieczyslaw , Lannfelt Lars
Published: April 2003

The apolipoprotein E (APOE) gene has in many studies been identified as a susceptibility factor in Alzheimer’s disease (AD). The APOE association is rather strong, but other not yet identified genetic factors are assumed to be involved in the pathogenesis of AD. Recently an association between an intronic polymorphism in presenilin-1 (PS-1) gene and late-onset AD was claimed. In order to confirm this observation we studied a sample of Polish patients with sporadic AD. However, our results did not confirm the existence of an association between the intronic polymorphism in the PS-1 gene and late-onset AD.
Decreased Immunosuppressive Effect of Cortisol on Natural Killer Cytotoxic Activity in Senile Dementia of the Alzheimer Type
Authors: Solerte Sebastiano Bruno , Cerutti Nadia , Severgnini Silvia , Rondanelli Mariangela , Ferrari Ettore , Fioravanti Marisa
Published: April 2003

Former studies have indicated alterations of the cytotoxic activity of natural killer (NK) cells in senile dementia of the Alzheimer type (SDAT). These changes may be related to the increased reactivity of NK cells with cytokines, even if an impairment of the immunosuppressive effect of glucocorticoids cannot be excluded. In the present study we have demonstrated a lower immunosuppressive effect of cortisol on NK cytolytic function in patients with SDAT than in healthy elders and in patients with dementia of multi-infarct origin (MID). This suppression is completely lacking when cortisol is employed at low concentrations (10–7 M) and is significantly reduced after incubation at physiological (10–6 M; p < 0.001) and supraphysiological concentrations (10–5 M; p < 0.001). The addition of IL-2 (50 and 100 IU/ml/cells) significantly antagonizes the effects of cortisol in SDAT, whereas the cortisol-dependent immunosuppression is partially maintained in healthy elders and in patients with MID. Our data indicate that the defect of the immunosuppressive effect of cortisol may play a role in NK dysregulation in SDAT, contributing to the cytokine-mediated NK overactivity in this disease.
Differentiating Alzheimer’s Disease and Frontotemporal Dementia: Receiver Operator Characteristic Curve Analysis of Four Rating Scales
Authors: Hooten W. Michael , Lyketsos Constantine G.
Published: April 2003

Alzheimer’s disease and frontotemporal dementia are two of the most common types of degenerative dementia. In conjunction with a complete neuropsychiatric examination, the Executive Interview©, Mini-Mental State Exam, Alzheimer’s Disease Scale, Pick’s Disease Scale and the Informant-Based Questionnaire have been used to distinguish between these two disorders on clinical grounds. In a review of two studies, scores from these rating scales are subjected to receiver operator characteristic curve analysis to determine the cut-off value for each scale which yields the highest sensitivity and specificity with regard to differentiating between Alzheimer’s disease and frontotemporal dementia. Finally, the Informant-Based Questionnaire is discussed and compared to each rating scale to demonstrate the important features and limitations of each.
Apo E and Apo CI Loci Are Associated with Dementia in Younger But Not Older Late-Onset Cases
Authors: Tysoe C. , Galinsky D. , Robinson D. , Brayne C. , Huppert F.A. , Dening T. , Paykel E.S. , Easton D.F. , Rubinsztein D.C.
Published: April 2003

Numerous groups have confirmed that apolipoprotein E allelic variation accounts for a proportion of the genetic risk for late-onset Alzheimer’s disease (AD). However, there is a paucity of data on the impact of this locus on the overall risk of dementia (as opposed to AD) in the elderly. Most studies have ascertained specifically AD cases from hospital clinics or brain banks and many demented cases have vascular dementia or mixed AD and vascular pathology. We have examined the closely linked apo E and apo CI loci in demented cases and non-demented controls from two community-based aged Cambridgeshire populations: the rural Ely population (cohort 1) comprised 60 pairs of demented and non-demented elderly individuals, with a mean age of 84.2 years (SD = 6.11); the Cambridge city population (cohort 2) comprised 81 pairs all aged over 84 with a mean age of 87.7 years (SD = 2.9). The younger Ely cohort showed significant allelic associations with dementia at the apo E and apo CI loci, which were not replicated in the older Cambridge cohort. These data suggest the possibility of age-dependent penetrance for different candidate genes in late-onset dementia. We propose a number of explanations to account for the stronger associations we observed between dementia and apo CI, compared to the neighbouring apo E locus. Our data are compatible with the possibility that specific alleles or genotypes may confer different risks for overall dementia, compared to AD.
Longitudinal EEG Findings in Dementia Related to the Parietal Brain Syndrome and the Degree of Dementia
Authors: Edman Åke , Matousek Milos , Sjögren Magnus , Wallin Anders
Published: April 2003

EEG slow-wave activity was correlated with the regional brain syndrome profile in 74 patients with dementia. The EEGs were visually assessed using a semiquantitative rating scale. The intensities of four regional brain syndromes (parietal, frontal, subcortical, global) and the degree of dementia were rated. The patients were examined twice with a 1-year interval. A significant relationship was found between the increase in EEG slow-wave activity and the increase in intensity of the parietal brain syndrome. A somewhat lower significance was found for the relation between increase in slow-wave activity and increase in dementia degree. The results suggest that the EEG deterioration in dementia mainly reflects the gradual decline of parietal brain function.
Effect of Presentation Rate on Word List Learning in Patients with Dementia of the Alzheimer Type
Authors: Heun R. , Burkart M. , Wolf C. , Benkert O.
Published: April 2003

The efficacy of simple interventions for the improvement of memory performance in patients with dementia of Alzheimer type (DAT) has rarely been evaluated. Therefore, we examined the effects of presentation duration and task practice on word list learning in this sample: 19 patients with DAT and 21 control subjects (with remitted major depression) repeatedly performed modifications of a word list learning task using five different presentation durations (i.e. 1, 2, 5, 10 or 20 s/word). In agreement with previous observations, prolonged visual presentation of words significantly improved recall and recognition in demented subjects, whereas task practice did not improve memory performance. The performance in the demented sample after long presentation times (20 s/item) does not reach the level of performance of the comparison group after short presentation times (1 s/item). Consequently, it seems unlikely that memory dysfunction is caused by increased item processing times in patients with dementia. To reach comparable performance of demented and controls for intervention or activation studies, presentation times must be shortened below 1 s/item in the control sample.
Predictors of Longitudinal Changes in Memory, Visuospatial, and Verbal Functioning in Very Old Demented Adults
Authors: Small Brent J. , Bäckman Lars
Published: April 2003

Longitudinal changes in memory, visuospatial and verbal functioning in a sample of demented persons were examined. The role of several demographic, psychometric, and biological indices in predicting the rate of cognitive deterioration was also investigated. The sample consisted of 31 very old (mean age at entry = 83.5 years, range = 75–95) persons with Alzheimer’s disease (n = 22) and vascular dementia (n = 9) from a community-based study. Subjects were tested on two occasions separated by approximately 2.5 years. Results indicated significant longitudinal decline in verbal fluency and visuospatial ability, but only on 1 of 3 measures of episodic memory. Results from regression analyses indicated that a variety of putatively important variables, including age, gender, education, digit span, as well as a number of biological (vitamin B12, TSH), dementia etiology, and psychometric (digit span) indicators, exhibited no relationship to rate of memory, visuospatial, or verbal decline. The results suggest that the rate of cognitive deterioration in dementia is highly variable, and this variability in change appears to include a variety of characteristics. A possible reason thereof may be that the role of individual-difference variables for cognitive functioning in dementia is overshadowed by the pathogenetic process itself.
Identification of Cognitive Impairment in the Elderly: Homocysteine Is an Early Marker
Authors: Lehmann Martin , Gottfries C.G. , Regland Björn
Published: April 2003

In 336 consecutive patients attending a university-affiliated memory unit, clinical and psychological findings, neuroimaging and laboratory tests were analyzed. The patients were diagnosed with early Alzheimer’s disease 3%, senile dementia (SDAT) 16%, vascular dementia (VAD) 20%, other dementias 9%, minor cognitive impairment (dysmentia) 32% and subjective symptoms only 21%. Increases in vascular risk factors, serum homocysteine, ApoE4 load and neuroimaging pathology were found in dementia but also in dysmentia and in patients with subjective symptoms only. The homocysteine levels correlated inversely with cognitive performance. The increases in serum homocysteine, which were pathological in VAD, Dysmentia and SDAT, may be indicative of a disturbed cerebral one-carbon metabolism and signal-accelerated development of cognitive disease.
Reduced Number of Caudate Nucleus Dopamine Uptake Sites in Vascular Dementia
Authors: Allard Per , Englund Elisabet , Marcusson Jan
Published: April 2003

The dopamine (DA) uptake sites in the caudate nucleus were studied in patients with vascular dementia (VAD) and in a control group using the presynaptic DA uptake site marker [3H][2β-carbomethoxy-3β-(4-fluorophenyl) tropane] as radioligand. There was a significant decrease in the number of DA uptake sites in the VAD group, while the binding affinity was unchanged. The present results indicate that in the patients investigated, the cerebrovascular disease process involves dopaminergic neuron terminals in the caudate nucleus. Our findings are discussed in relation to the reductions in number of DA uptake sites that have previously been revealed in Alzheimer’s and Parkinson’s diseases.
Aminotransferase Levels and Silymarin in de novo Tacrine-Treated Patients with Alzheimer’s Disease
Authors: Allain H. , Schück S. , Lebreton S. , Strenge-Hesse A. , Braun W. , Gandon J.M. , Brissot P.
Published: April 2003

Background: Silymarin is a well-known hepatoprotective agent. Tacrine, the first drug marketed for Alzheimer’s disease (AD), induces an elevation of serum liver transaminase prohibiting an effective dosage in many patients. This 12-week randomised, double-blind, placebo-controlled study was undertaken to evaluate the ability of silymarin to antagonise or prevent the hepatotoxic effects of tacrine and to analyse its action on tacrine efficacy and tolerability. Methods: Outpatients suffering from mild-to-moderate dementia of the Alzheimer type were randomly assigned to two treatment groups: tacrine + silymarin and tacrine + placebo. The study was double-blind for silymarin and open for tacrine and was conducted in 22 French neurology and geriatric centres. Silymarin (420 mg/day) was given first (1 week) and tacrine was added at 40 mg/day for 6 weeks, then increased to 80 mg/day (6 weeks). Serum ALAT was the main evaluation criterion (> upper limit of normal, ULN). Serum ASAT as well as adverse side effects and cognitive performance assessed by MMSE and the Syndrome Kurtz test (SKT) were secondary evaluation criteria. Null hypotheses were evaluated with Fisher’s exact test. Findings: 222 patients were recruited and received silymarin and tacrine (110 patients) or placebo and tacrine (112 patients). 28 patients dropped out; 217 were included in the intent-to-treat analysis. No statistical difference was observed between the two groups for serum ALAT (p = 0.39). Fewer patients had ALAT levels >5 ULN in the silymarin group (–33.3%). Side effects and notably gastrointestinal disorders were much less frequent in the silymarin group. Cognitive performance remained unchanged in both groups. Interpretation: Silymarin does not prevent tacrine-induced ALAT elevation but does reduce the rate of gastrointestinal and cholinergic side effects without any impact on cognitive status. As a consequence, silymarin (420 mg/day) could be co-administered with tacrine to improve tolerability in the initial phases of AD treatment.
Lack of Genetic Associations of Alpha-1-Antichymotrypsin Polymorphism with Alzheimer-Type Neuropathological Changes or Sporadic Alzheimer’s Disease
Authors: Sodeyama Nobuyuki , Yamada Masahito , Itoh Yoshinori , Suematsu Naomi , Matsushita Masaaki , Otomo Eiichi , Mizusawa Hidehiro
Published: April 2003

To elucidate the influence of the α1-antichymotrypsin (ACT) polymorphism on Alzheimer-type neuropathological changes and the development of sporadic Alzheimer’s disease (AD), we studied the relationship between the ACT polymorphism and the severity of Alzheimer-type neuropathological changes in the brains from AD patients and nondemented subjects. There was no association of the ACT polymorphism with Alzheimer-type neuropathological changes in AD or nondemented individuals. ACT polymorphism was not associated with the development of AD. These results remained nonsignificant when the ACT genotype groups were divided into subgroups according to the apolipoprotein E (ApoE) σ4 status. Our study shows that the ACT polymorphism has no effect on Alzheimer-type neuropathological changes or the development of AD, either alone or in combination with ApoE σ4.
Progressive Dysarthria
Authors: Santens P. , van Borsel J. , Foncke E. , Meire V. , Merkx H. , de Bleecker J. , De Reuck J.
Published: April 2003

Two patients presenting with progressive dysarthria as the single initial manifestation of a neurodegenerative condition are described. The nature of the dysarthria as well as the additional symptoms that developed in the course of the disorder are very different in these two cases. Nevertheless, neuroimaging findings are strikingly similar and suggest bilateral involvement of posterior inferior frontal lobe structures, mainly in the dominant cerebral hemisphere. The clinical syndrome of these patients can therefore be considered an example of frontotemporal degeneration presenting without dementia or comportmental alteration, at least in the early stages. This broadens the clinical spectrum of frontotemporal degeneration and demonstrates the need for a syndromal subclassification of this nosological entity.
The Effects of Donepezil in Alzheimer’s Disease – Results from a Multinational Trial1
Authors: Burns A. , Rossor M. , Hecker J. , Gauthier S. , Petit H. , Möller H.-J. , Rogers S.L. , Friedhoff L.T.
Published: April 2003

Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer’s disease (AD). The current trial was undertaken to investigate further the efficacy and safety of donepezil, in a multinational setting, in patients with mild to moderately severe AD. This 30-week, placebo-controlled, parallel-group study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment with single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC plus). Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterioration in Daily living activities in Dementia (IDDD) and a patientrated quality of life assessment. Statistically significant improvements in cognitive and global function were observed, as evaluated by ADAS-cog and CIBIC plus, respectively, in both the 5 and 10 mg/day donepezil groups, compared with placebo. Treatment-associated changes were also observed in functional skills, as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD. A dose–response effect was evident, with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormalities. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD.
The Role of the Polymorphic Genes Apolipoprotein E and Methylene- tetrahydrofolate Reductase in the Development of Dementia of the Alzheimer Type
Authors: Regland Björn , Blennow Kaj , Germgård Thore , Koch-Schmidt Ann-Christine , Gottfries Carl-Gerhard
Published: April 2003

The gene for apolipoprotein E (APOE) is polymorphic, and its variant APOE4 is a major risk factor for the development of Alzheimer-type dementia (AD). Another risk factor for AD appears to be negative cobalamin balance, which is very common in elderly people. Cobalamin and folate are interdependent and essential components of the one-carbon metabolism. Another important component is methylenetetrahydrofolate reductase (MTHFR), the gene for which is also polymorphic. Thermolabile MTHFR (tMTHFR), a gene variant that reduces the activity of its enzyme, is common in the general population. In the present study, 75% of 140 AD patients had at least one APOE4 allele. The numbers of APOE4 and tMTHFR alleles correlated significantly with the serum folate levels, however, in opposite directions. The significance of this was augmented by an inverse correlation between APOE4 and tMTHFR. Thus, not only MTHFR but also APOE appears to be related to the one-carbon metabolism, suggesting that APOE4 and insufficient one-carbon metabolism may be synergistic risk factors for AD.
Early-Onset and Late-Onset Depression Are Independent of the Genetic Polymorphism of Apolipoprotein E
Authors: Papassotiropoulos Andreas , Bagli Metin , Jessen Frank , Rao Marie Luise , Schwab Sibylle G. , Heun Reinhard
Published: April 2003

The recently shown association between apolipoprotein E (APOE) genotype and depressive illness has been challenged by subsequent studies. However, controversial results may derive from the different diagnostic criteria used for depression and from the small numbers of depressed patients included in the studies. We examined the association between depression and the genetic polymorphism of APOE in a large sample of depressed patients, Alzheimer’s disease (AD) patients, and healthy controls following clear definitions for late-life depression. The cumulative incidence of depression depending on the age at onset of the first episode was examined by survival analysis. Our data do not disconfirm the hypothesis of depression sharing some common pathophysiologic features with AD, however, it seems very unlikely that the APOE genotype will elucidate the assumed common mechanisms.
A Double-Blind, Placebo-Controlled Study of Tacrine in Chinese Patients with Alzheimer’s Disease
Authors: Wong Wen-Jang , Liu Hsiu-Chih , Fuh Jong-Ling , Wang Shuu-Jiun , Hsu Li-Chi , Wang Pei-Ning , Sheng Wen-Yung
Published: April 2003

The purpose of the study was to evaluate the efficacy and safety of tacrine over 30 weeks in Chinese patients with probable Alzheimer’s disease (AD). A total of 100 patients with mild to moderate AD were recruited and randomly assigned to active or placebo treatment. The active group received 30 mg/day of tacrine for the first 6 weeks, 60 mg/day for the next 6 weeks, 90 mg/day for 6 more weeks and then 120 mg/day for the remaining 12 weeks. Safety evaluations included biweekly determinations of alanine aminotransferase (ALT). The primary outcome measures were Cognitive Abilities Screening Instrument (CASI), Clinical Global Impression of Change (CGIC) by investigator and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Secondary outcome measures were Mini-mental State Examination (MMSE), Alzheimer’s Deficit Scale (ADS) and CGIC by caregivers. Sixty-eight patients were included in an intent-to-treat analysis (48 active and 20 placebo); 56 patients had evaluable data at week 30 (36 active and 20 placebo). The results of the complete case analysis revealed a significant improvement in the CASI and MMSE scores of the active group in the 18th week (90 mg/day) and the 30th week (120 mg/day) (p < 0.01). In the intent-to-treat analysis, significant improvement of the active group was noted on CASI at week 30 (p = 0.05), but there was no significant difference in the measures of IQCODE, CGIC and ADS. The primary reasons for withdrawal of tacrine-treated patients (39 patients, 52%) were asymptomatic ALT elevation, anorexia and nausea/vomiting. These patients all recovered from the adverse events on discontinuation of treatment. Tacrine produced a statistically significant improvement in the CASI and MMSE in Chinese patients with mild to moderate AD using a lower dose than in western people.
Acetylcholine and Delirium
Authors: Tune Larry E. , Egeli Susan
Published: April 2003

The neurotransmitter acetylcholine has been implicated in animal and human studies of delirium. This chapter will briefly review the clinical studies focussing on measurement of serum levels of anticholinergic activity in delirious states. Three approaches have been taken. First, to identify medications currently prescribed that have subtle anticholinergic effects. The current ‘list’ includes 48 commonly prescribed medications. Second, to associate serum anticholinergic activity with delirium in various clinical states including postcardiotomy delirium, postelectroconvulsive delirium, delirious elderly medical inpatients, and nursing home patients. Third, to intervene in patients with elevated anticholinergic activity by reducing known anticholinergics and correlating this reduction with clinical measures of cognition and delirium. Our most recent data investigates the impact of anticholinergics on demented patients. Rates of delirium were significantly higher in patients receiving larger numbers of anticholinergics.
What Criteria Should Be Used for the Diagnosis of Delirium?
Authors: Liptzin Benjamin
Published: April 2003

DSM-IV made several revisions to the diagnostic criteria for delirium. This paper reviews the empirical data that supported these revisions. More research is needed to evaluate the usefulness of the new criteria and to further define subtypes of delirium.
Delirium in Clinical Practice: Experiences from a SpecializedDelirium Ward
Authors: Wahlund Lars-Olof , Björlin Gunilla Armanius
Published: April 2003

Geriatric patients with known dementia and suffering from an acute somatic disease are highly vulnerable to develop delirium. It is therefore essential to suspect and recognize delirium in these patients, especially in emergency wards. In the present study we evaluated activities on a dedicated delirium ward at a Swedish University Hospital. Over one and a half years 637 patients were treated for suspected delirium, the majority of patients being referred from the emergency ward at the same hospital. Infectious diseases were the main cause of delirium in 67% of cases. Other common causes were heart disease and stroke. Drug use as the only cause of delirium was found in less than 1% of cases. Approximately 70% of patients had cognitive disturbances, either dementia or mild cognitive impairment. The existence of multiple diseases as causative factors was frequent. Knowledge about delirium and how it is both diagnosed and treated is of great importance in all kinds of settings where acute somatic treatments are common.
Delirium: Effectiveness of Systematic Interventions
Authors: Cole Martin G.
Published: April 2003

The purpose of this paper was to review evidence related to the effectiveness of systematic interventions in preventing or detecting and treating delirium. The review process involved a systematic search of the literature on each topic, assessment of the validity of the studies retrieved and examination of their results. The literature search identified 10 studies on prevention and 7 studies on detection and treatment. A broad spectrum of systematic interventions appeared to be modestly effective in preventing delirium in young and old surgical patients but not elderly medical patients. Systematic detection and treatment programs and special nursing care appeared to add large benefits to traditional medical care in young and old surgical patients and modest benefits in elderly medical patients; however, it seemed that the more precise the target of the detection and treatment program, the greater the benefit.
NADPH-Diaphorase-Containing Neurons in Cortex, Subcortical White Matter and Neostriatum Are Selectively Spared in Alzheimer’s Disease
Authors: Tao Zhen , van Gool Dominique , Lammens Martin , Dom René
Published: April 2003

To investigate the involvement of NADPH-diaphorase (NADPH-d)-containing neurons in Alzheimer’s disease (AD), NADPH-d enzyme histochemistry in vibratome sections was applied to the superior frontal and superior temporal cortex and the neostriatum in 5 AD and 6 aged control brains. Overall there was a neuronal loss and atrophy in the cortex of AD. Despite slight morphological neuronal changes in the cortex of AD, we found no significant difference in the number of NADPH-d-positive neurons in both cortex and neostriatum between control and AD cases. These results provide further evidence for a selective preservation of NADPH-d neurons in AD. In order to check whether nNOS-immunoreactive neurons are identical to NADPH-d-positive neurons in the human brain, we examined the frontal and temporal cortex and neostriatum of normal human brains in serial cryostat sections. We found that nNOS-containing neurons paralleled NADPH-d-positive neurons in these brain regions.
A Longitudinal Quantitative EEG Study of Alzheimer’s Disease: Relation to Apolipoprotein E Polymorphism
Authors: Lehtovirta Maarit , Partanen Juhani , Könönen Mervi , Hiltunen Jaana , Helisalmi Seppo , Hartikainen Päivi , Riekkinen Sr Paavo , Soininen Hilkka
Published: April 2003

Apolipoprotein E (apoE) σ4 allele is a risk factor for late-onset Alzheimer’s disease (AD) and is proposed to have an impact on cholinergic function in AD. Slowing of the EEG is characteristic in AD and the cholinergic system has an important role in modulating EEG. QEEG was recorded from 31 AD patients at the early stage of the disease and after a 3-year follow-up. AD patients were divided into subgroups according to the apoE σ4 allele (2σ4, 1σ4 and 0σ4). AD subgroups did not differ in clinical severity or duration of dementia. The AD patients carrying the σ4 allele had more pronounced slow-wave activity than AD patients without the σ4 allele, although the progression rate did not change. The differences in EEG may suggest differences in the degree of the cholinergic deficit in these subgroups.
Deterioration of Controlled Processes in the Preclinical Phase of Dementia: A Confirmatory Analysis
Authors: Amieva Hélène , Rouch-Leroyer Isabelle , Fabrigoule Colette , Dartigues Jean-François
Published: April 2003

Preclinical deficits in dementia have recently been investigated in the PAQUID cohort by means of a principal component analysis (PCA) performed from various test scores. According to the interpretation of the first PCA factor, which was found to be an independent predictor of dementia 2 years later, the authors suggested that cognitive deficits occurring in the preclinical phase of dementia may reflect the deterioration of controlled processes. Because this hypothesis relies essentially on the interpretation of PCA factors, the present study was designed to test it within the same cohort. The analyses were focused on one of the tests administered to the subjects, the Wechsler Paired Associate Test (WPAT) divided into two subscores in order to provide a measure of controlled processes of memory functioning (i.e. retrieval of unrelated pairs) as well as of more automatic processes (i.e. retrieval of related pairs). The results showed that the future demented subjects, although significantly impaired compared to elderly controls, were able to increase their performance across trials. More importantly, a new PCA including the subscores of the WPAT showed that the unrelated pair scores were strongly correlated to factor 1, which remained the only factor associated with subsequent dementia, whereas the related pair scores were rather correlated to factor 2. Therefore, these results confirm our previous PCA interpretation, lending more weight to our hypothesis of a preclinical impairment of controlled processes in dementia.
Apolipoprotein E Genotype and Lipid and Lipoprotein Levels in Dementia
Authors: Wehr H. , Parnowski T. , Puzyński S. , Bednarska-Makaruk M. , Bisko M. , Kotapka-Minc S. , Rodo M. , Wołkowska M.
Published: April 2003

In 64 individuals with dementia (26 Alzheimer type, 34 of vascular origin and 4 other types of dementia) apolipoprotein E genotype was identified. Frequency of ε4 allele was 36.5% in Alzheimer patients and 32.4% in vascular dementia ones. In a group of 39 nondemented individuals of the same age the ε4 frequency was 11.5%. In demented patients, carriers of ε4, a tendency to higher plasma levels of atherogenic lipids (total cholesterol and low-density lipoprotein cholesterol) as compared with noncarriers was observed. It is possible that the ε4 form may aggravate the course of dementia through a moderate influence on the atherogenic lipoprotein level. The results showed that both Alzheimer disease and vascular dementia shared the same risk factors which is consistent with current opinion about a link existing between these two types of dementia.
A Single-Photon Emission Computed Tomography Imaging Study of Driving Impairment in Patients with Alzheimer’s Disease
Authors: Ott Brian R. , Heindel William C. , Whelihan William M. , Caron Mark D. , Piatt Andrea L. , Noto Richard B.
Published: April 2003

Single-photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination (MMSE). Driving impairment in Alzheimer’s disease is related to changes in cortical function which vary according to the severity of the disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the MMSE that are weighted toward left-hemisphere-based verbal tasks.
Comparison between Multiple Lacunar Infarcted Patients with and without Dementia in Nursing Homes in Shimane Prefecture, Japan
Authors: Seno Haruo , Ishino Hiroshi , Inagaki Takuji , Yamamori Chikako , Miyaoaka Tsuyoshi
Published: April 2003

We evaluated the activity of daily living (ADL) scores, the frequency of hypertension (HT) and diabetes mellitus (DM), and the frequency and distribution of white matter lesions in a vascular dementia group with multiple lacunar infarctions (VD group; 20 cases) and a nondemented group with multiple lacunar infarctions (non-D group; 32 cases), relative to a normal control group (29 cases). There were no significant differences in HT and DM among the three groups. ADL scores were significantly lower in the VD than in the non-D group, each of which was lower than in the control group. Frequency of white matter lesions (Binswanger’s disease-like lesions in the frontal and parietal lobes) was significantly higher in the VD than in the non-D group, which was higher than in the control group. We believe that for dementia with multiple lacunar infarctions, diffusely affected cerebrum including white matter lesions, which results in low ADL scores for symptoms, may be a prerequisite.
White Matter Lesions in Dementia: An MRI Study on Blood-Brain Barrier Dysfunction
Authors: Bronge Lena , Wahlund Lars-Olof
Published: April 2003

White matter lesions (WMLs) and blood-brain barrier (BBB) dysfunction are common in dementia. Both conditions may be a consequence of small-vessel disease, in which case the BBB damage would be suspected to be located to the WMLs. To further evaluate the nature of WMLs in dementia we examined 10 demented patients with WMLs, including 5 cases with elevated CSF/serum albumin ratios as an indication of BBB damage. An optimised gadolinium (Gd)-enhanced MRI technique was used including a double dose of Gd, a 30-min scan time after injection and analysis of the MR signal in the WMLs as a function over time. Results showed no significant changes in MR signal in the WMLs after contrast administration. We conclude that WMLs are not connected to BBB damage to such a degree that is detectable with this method and that the elevated CSF albumin might have another origin.
Relation between Cerebral Blood Flow and Extracellular Glucose in Rat Striatum during Mild Hypoxia and Hyperoxia
Authors: Lowry John P. , Demestre Maria , Fillenz Marianne
Published: April 2003

Rats were exposed to mild hyperoxia and hypoxia by the administration of oxygen/air and nitrogen/air mixtures through plastic tubing held close to their snouts for periods of 3 min. Changes in tissue oxygen were monitored at an implanted carbon paste electrode; local cerebral blood flow (rCBF) at an implanted platinum electrode using the hydrogen clearance technique; extracellular brain glucose at an implanted glucose oxidase-based biosensor and changes in lactate were measured using microdialysis. The nitrogen/air mixture led to a decrease in tissue oxygen, an increase in rCBF, a decrease in extracellular glcuose, and an increase in lactate. The oxygen/air mixture led to an increase in tissue oxygen and extracellular glucose but no change in lactate or rCBF. The effects in unanaesthetised rats were compared with those in rats given 350 mg/kg cloral hydrate. The increase in lactate was greater in unanaesthetised than anaesthetised rats. The results show a dissociation between changes in rCBF and extracellular glucose and suggest that changes in oxygen affect utilisation rather than supply of glucose to the extracellular compartment.
The Sequence of Formation and Development of Corticostriate Connections in Mice
Authors: Sheth Ami N. , McKee Mary L. , Bhide Pradeep G.
Published: April 2003

We examined the development of the corticostriate pathway in mice by labeling corticofugal axons with the carbocyanine dye 1,1′-dioctadecyl-3,3,3′-3′-tetramethylindocarbocyanine perchlorate (DiI). Growth cones of corticofugal axons enter the developing striatum on embryonic day 12 (E12; conception is on E0). By E15 corticofugal axons pass through the developing striatum in the internal capsule but do not produce striatal collaterals. Corticostriate collaterals are seen for the first time on E18, 6 days after the earliest arriving axons enter the striatum. At that time, presumptive synaptic contacts form between cortical axons and striatal neurons. Corticostriate collaterals arise from corticofugal axon trunks at or near axonal varicosities. Primitive corticostriate arbors form by postnatal day 2 (P2; day of birth is P0) and develop further by P7. Thus, corticostriate connections develop in three morphologically defined stages: first cortical axons elongate through the striatum to other subcortical targets, next they produce striatal collaterals, and finally they elaborate terminal arbors. The transition from elongation to collateralization stage may be triggered, among other factors, by signals from striatal neurons relayed via the synaptic contacts.
Brain ATP Metabolism in Hypoxia Resistant Mice Fed Guanidinopropionic Acid
Authors: Holtzman D. , Brown M. , O’Gorman E. , Allred E. , Wallimann T.
Published: April 2003

Feeding β-guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, decreases mortality and increases brain ATP stability in hypoxic mice. To study brain ATP metabolism in GPA-fed animals, respiratory rates were measured in grey matter and white matter slices as well as cerebral hemisphere mitochondria from GPA-fed mice and rats. Creatine kinase and adenylate kinase activities were measured in rat cerebral grey matter and white matter. Respiratory rates and oxidative phosphorylation were the same in GPA-fed mice and control mice. The adenylate kinase activity increased 50% and creatine kinase showed a small decrease in grey matter. In white matter, creatine kinase increased 50% while adenylate kinase decreased. Thus, GPA produces opposite adaptive changes in adenylate kinase and creatine kinase in grey matter and in white matter. These results suggest that the creatine kinase reaction in grey matter acts to regulate cellular ADP and ATP concentrations.
Dose-Dependent Effects of Multiple Acute Cocaine Injections on Maternal Behavior and Aggression in Sprague-Dawley Rats
Authors: Johns Josephine M. , Nelson Christina J. , Meter Kathleen E. , Lubin Deborah A. , Couch C. Destine , Ayers Andy , Walker Cheryl H.
Published: April 2003

Rat dams, which had no prior drug treatment, were either nontreated controls or were injected subcutaneously 4 times during a 10-day period with a single dose of 30, 15 or 7.5 mg/kg of cocaine hydrochloride HCl, or normal saline. Injections were given immediately postpartum following delivery of their final pup (PPD 1), and again on postpartum day 3 (PPD 3), postpartum day 6 (PPD 6) and postpartum day 10 (PPD 10). Dams were observed 30 min following injections for maternal behavior (MB) towards 8 surrogate male pups on PPD 1 and PPD 3 and for aggression towards a male or female intruder in the presence of their litter on PPD 6 and PPD 10. Compared to saline and untreated controls, cocaine-treated dams exhibited more disruptions in MB on both PPD 1 and PPD 3 and were less aggressive towards an intruder, regardless of intruder sex, on PPD 6 and PPD 10. In most cases MB was altered in a dose-dependent manner with the higher doses of cocaine resulting in a greater disruption of behavior.
Myelin Proteolipid Protein: Function in Myelin Structure Is Distinct from Its Role in Oligodendrocyte Development
Authors: Nadon Nancy L. , West Melinda
Published: April 2003

The myelin proteolipid proteins PLP and DM20 are essential for the compaction of central nervous system myelin and they play an important role in the maturation of the oligodendrocyte. The specific function of the less abundant DM20 isoform is still unknown, but rescue experiments previously indicated that both isoforms are necessary for oligodendrocyte maturation. In vitro experiments have suggested DM20 may assist in the translocation of PLP into the membrane. We tested this hypothesis in vivo, by investigating whether wild-type PLP derived from a transgene could be incorporated into the myelin membrane of Plp mutant rumpshaker mice. We previously demonstrated that expression of the PLP transgene alone in a more severe Plp mutant, jimpy mouse, did not result in PLP incorporation into the myelin. Here we report that there was significantly more PLP in white matter from rumpshaker expressing the PLP transgene than their nontransgenic rumpshaker littermates and that myelin structure was improved. The delay in oligodendrocyte development was not alleviated by expression of the PLP transgene however, supporting an essential role for DM20 in oligodendrocyte maturation.