bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive Astrocytes Express Acidic Fibroblast Growth Factor in Alzheimer's Disease Brain
Authors: Yasuhara Osamu , Tooyama Ikuo , Akiyama Haruhiko , Akiguchi Ichiro , Kimura Jun , McGeer Patrick L. , Hara Yasushi , Kimura Hiroshi
Published: August 2007

Localization of acidic fibroblast growth factor (aFGF) was investigated immunohistochemically in postmortem brain tissue of Alzheimer''s disease (AD), amyotrophic lateral sclerosis (ALS), and age-matched control cases using a specific rabbit antiserum to aFGF. Small numbers of glial cells were faintly stained in white but not gray matter of control cases. Larger numbers of reactive astrocytes were stained intensely for aFGF in severely affected areas of AD cases and in the primary motor cortex of ALS cases. In AD, aFGF-positive astrocytes congregated at the margin of senile plaques. Double immunostaining indicated that such upregulation of aFGF expression might be related to the presence of reactive microglia rather than β-amyloid protein deposits.
Neurohormones in the Hypothalamo-Hypophysial System in Senile Dementia of the Alzheimer Type
Authors: Yates Celia M. , Fink George , Bennie John , Wilson Helen , Carroll Sheena , Harmar Anthony J. , Hunter Robert , Gordon Alexander
Published: August 2007

Oestrogen-stimulated neurophysin (ESN), oxytocin (OXY), nicotine-stimulated neurophysin (NSN), arginine vasopressin (AVP), somatostatin (SS) and growth hormone-releasing hormone (GHRH) were measured in post-mortem dorsal and basal hypothalamus and pituitary stalk from cases of senile dementia of the Alzheimer type (SDAT) and age-matched controls and in pituitary stalk from cases of mixed SDAT/cerebrovascular dementia. The 6 neurohormones were also measured in pituitary glands from cases of SDAT, other dementias and age-matched controls. ESN, OXY, NSN and AVP were unaltered in the hypothalamus and pituitary stalk of the SDAT cases and in the pituitary stalk of the mixed SDAT/cerebrovascular cases. The concentrations of NSN and AVP were lower in pituitary glands from 8 controls who were terminally ill than in 5 controls who had died suddenly. Between-group comparisons of terminally ill cases showed that ESN, OXY, NSN and AVP were reduced in pituitary glands from 12 SDAT cases and that NSN and AVP were reduced in glands from 9 cases of other dementias. SS and GHRH were unaltered in the hypothalamus, and GHRH was unaltered in the pituitary stalk, of 19 SDAT cases compared with 18 controls. Reduced levels of SS in the pituitary stalk of the SDAT group could be attributed to terminal illness, since terminally ill controls had lower pituitary stalk SS concentrations than controls who had died suddenly. The major form of SS in the hypothalamus was somatostatin-14, whereas the major form in pituitary stalk was somatostatin-28, suggesting that somatostatin-28 may have a specific role in the control of hormone secretion from the adenohypophysis. Our ESN, OXY, NSN and AVP data suggest that whilst synthesis and transport of the hypothalamo-neuro-hypophysial hormones are unaffected in SDAT, storage of these hormones in the neurohypophysis may be reduced in SDAT and other dementias.
On the White Matter Changes in Spongiform Encephalopathy
Authors: Cruz-Sánchez Félix F. , Ferrer Isidro , Rossi Marco L.
Published: August 2007

Two males and 2 females aged between 37 and 78 years clinically diagnosed as suffering from Creutzfeld-Jakob disease (CJD) were studied. The evolution of the disease from onset of symptoms to death varied between 2 and 48 months. CT scan on admission showed a slight diffuse cortical atrophy in 2 cases. Repeat CT scans showed progressive cortical atrophy in 4 cases, while in 2 cases mild to moderate diffuse hypodense white matter lesions were seen. Neuropathological findings demonstrated classical histological changes of CJD in the gray matter. The white matter showed diffuse demyelination and areas of focal pallor except for the internal capsule, which was spared in all cases. Histologically the white matter changes consisted of spongiform changes with proliferation of hypertrophic astrocytes and depletion of oligodendrocytes with myelin loss. Immunohistological staining for myelin basic protein showed granular degeneration in areas of diffuse demyelination and in discrete foci. Focal lesions with granulae of degenerated myelin, not appreciable in luxol fast blue stain, were also found with the myelin basic protein antibody. On the basis of our findings and those of others, we suggest that our cases are examples of a spongiform panencephalopathy in which host peculiarities may allow involvement of white matter to occur.
Affective and Cognitive Symptoms in the Aged in a Japanese Nursing Home
Authors: Kashiwase Hirotaka , Watanabe Masayuki , Suda Emiko , Tachibana Shoichi , Kinuya Masayuki , Ohtakeno Shinji , Watanabe Hiromi , Hotori Akira , Tatsunuma Toshihiko , Nagashima Kiichi
Published: August 2007

The authors examined the frequency and severity of dementia and depression in the elderly subjects referred to a nursing home for the aged in Japan using Hasegawa''s Dementia Scale (HDS) and Hamilton Rating Scale for Depression (HRSD). There were 29 (37%) nondemented comparison subjects (CS), 20 (26%) subjects with cognitive impairment due to physiological aging and 28 (36%) demented patients, including 9 (12%) cases of dementia of the Alzheimer type and 17 (22%) with multi-infarct dementia. One schizophrenic patient was also found. HRSD scores were significantly higher among patients with organic dementia than among CS and subjects with cognitive impairment due to physiological aging. The rate of depression (subjects with HRSD scores ≧ 11) in CS was 17% (5 of 29), and that of depression superimposed on dementia was 18% (5 of 28).
A Topographical Pathway by Which Histopathological Lesions Disseminate through the Brain of Patients with Alzheimer's Disease
Authors: Fewster Peter H. , Griffin-Brooks Sharon , MacGregor JoAnn , Ojalvo-Rose Ester , Ball Melvyn J.
Published: August 2007

The strength of earlier suggestions about the site where Alzheimer lesions first appear in the brain has been limited, since either too few brain regions or too few cases have been surveyed. We have therefore quantified the density of neuropathological lesions both in serially sectioned hippocampal and also in 10 neocortical regions from the brains of 45 demented patients dying with Alzheimer''s disease (AD) as well as 12 age-matched normal controls. Multivariate analysis and rank ordering confirm that the hippocampus is affected by Alzheimer changes before any parts of the neocortex. The histopathological effects of the disease then progress through the other temporal gyri, followed by frontoparietal and cingulate regions, and involve the sensorimotor and visual cortices only very late in the disorder. This gradual mode of spread through the brain favors the progressive neurone-to-neurone dissemination of an etiological trigger, such as a reactivated latent viral agent (e.g., Herpes simplex), rather than the simultaneous affliction of the entire central nervous system by a systemically circulating substance, such as a protein (e.g. β-amyloid) entering via a hematogenous route.
A Longitudinal Study of Dementia of Alzheimer Type in Down's Syndrome
Authors: Johanson A. , Gustafson L. , Brun A. , Risberg J. , Rosén I. , Tideman E.
Published: August 2007

The aim of the study was to elucidate whether clinical progress and neurophysiological changes in patients with Down''s syndrome (DS) are similar to the characteristic findings in patients with dementia of Alzheimer type (DAT). Twenty-two DS patients were evaluated in a longitudinal design with rating scales, psychometric testing, regional cerebral blood flow (rCBF) measurements and EEG. Six deceased patients all showed the Alzheimer type of encephalopathy. Comparisons between the first and final test results indicate that DS patients above 40 years of age displayed a marked decline of scores on rating scales and a progressive cognitive deterioration, involving spatial functions. Furthermore, the older patients showed significant rCBF decreases in parietotemporal areas in both hemispheres together with progressing EEG pathology. It is concluded that elderly patients with DS develop organic dementia with clinical and neuropathological characteristics similar to that in DAT without DS.
Depression in Dementia: Its Impact on Functional Ability
Authors: Agbayewa M. Oluwafemi , Weir Janine , Tuokko Holly , Beattie Lynn
Published: August 2007

Dementia and depression both affect the ability to function. There is little information on how these two disorders affect the abilities of Alzheimer disease (AD) patients to perform instrumental activities of daily living (IADLs). We explored this at the Clinic for Alzheimer''s Disease and Related Disorders at the University Hospital, UBC Site in Vancouver, Canada. Using the DSM IIIR and NINCDS-ADRDA criteria, we identified patients who met the criteria for AD and subdivided them into depressed and nondepressed based on the presence of major depression. These groups were then compared on their abilities in functional abilities and Minimental State Examination scores (MMSE). The sample consists of 14 depressed and 88 nondepressed AD patients. They did not significantly differ in age, social and occupational functioning, home and hobbies, personal care and measures of instrumental activities of daily living. The depressed group had symptoms for shorter periods of time (t = 3.52, d.f. = 36.52, p = 0.001) and higher MMSE scores (t = 2.63, d.f. = 100, p = 0.01). The two groups were further subdivided into two groups each based on ability to perform an IADL. MMSE scores differed significantly among the four resultant groups for all IADLs. There was no interaction between depression and ability to perform any of the IADLs. We conclude that the effect of dementia on IADLs was too dominant for depression to exert any further effect. The effect of depression often observed in the physically disabled may not be duplicated in the demented because of the different natures of the disabilities.
Deinstitutionalization and the Infirm Chronic Psychiatric Patient
Authors: Bleeker J.A.C. , De Reus R. , Duurkoop W.R.A.
Published: August 2007

In the Netherlands a tight network of mainly intramural psychogeriatric nursing facilities exists. A discussion is going on whether these beds may substitute beds for elderly infirm inpatients of psychiatric hospitals, which are more expensive. The move towards community psychiatry may lead to insufficient planning of services for patients with combined chronic mental and somatic conditions. Elderly patients in psychiatric hospitals and nursing homes show significant differences in psychopathology as well as ADL deficits. It is argued that in both types of facilities at present different categories of patient are taken care of. Planning of services should take into account different patterns of needs among elderly infirm mental patients. Dementia is in itself not a decisive factor in the allocation of patients to primary nursing homes or psychiatric facilities.
The Real Value of Electroconvulsive Therapy in the Elderly
Authors: Rosenvinge Henry
Published: August 2007

ECT studies in the elderly show its value in the treatment of severe depression and that the long term prognosis can be good. Patients suffering from severe depressive symptoms in dementia may also receive ECT with good short term effect. ECT is probably underused in the management of psychiatric disorders in Parkinson''s disease where both psychological and motor manifestations may improve. Treatment associated anxiety needs to be minimised in patients, ways of doing this are explored.
Disoriented Behavior in Familiar Surroundings Is Strongly Associated with Perceptual Impairment in Mild Alzheimer's Disease
Authors: Haupt Martin , Pollmann Stefan , Kurz Alexander
Published: August 2007

42 outpatients with mild Alzheimer''s disease were studied to investigate the hypothesis that neuropsychological measures which indicate right hemisphere dysfunction, like deficits in visuoconstructive and perceptual tasks, are associated with disoriented behavior in familiar surroundings. The only measure associated with disoriented behavior was the measure of perceptual impairment. Visuoconstructive, memory or verbal impairment were not related to disoriented behavior. Furthermore, when the influence of perceptual impairment was eliminated by calculating partial correlations, the other correlations between memory, visuoconstructive or verbal impairment and disoriented showed a substantial decrease. Our results suggest a strong association between perceptual impairment in neuropsychological measures and disoriented behavior in familiar surroundings in mild Alzheimer''s disease.
Effects of Estrogen Replacement Therapy on Cerebral Perfusion and Cognition among Postmenopausal Women
Authors: Funk Janice L. , Mortel Karl F. , Meyer John S.
Published: August 2007

Previous investigations concerned with effects of estrogen replacement therapy (ERT) in older women have focused primarily on morbidity and mortality as measures of outcome. A retrospective study is reported here that investigated the effects of ERT in older women with and without cerebrovascular disease on measures of cerebral perfusion and cognition. Results indicate that ERT was significantly correlated with higher cognitive test performance among women with a history of cerebrovascular disease. There was also a trend for increased cerebral perfusion among women with cerebrovascular disease receiving ERT. Results are consonant with previous reports that estrogen exerts ‘protective effects’ among patients with cerebrovascular disease and suggest that estrogen replacement may stabilize the deleterious effects of progressive cerebrovascular disease by helping to sustain cerebral perfusion and cognition among women with a history of cerebrovascular disease.
Reduced Lumbar Cerebrospinal Fluid Somatostatin Levels in Alzheimer's Disease and Dementia with Frontotemporal Degeneration
Authors: Minthon L. , Edvinsson L. , Ekman R. , Gustafson L.
Published: August 2007

The present study evaluates the cerebrospinal fluid levels of somatostatin-like immunoreactivity (LI) in two types of primary degenerative dementias: dementia of Alzheimer''s disease (DAT) and dementia with frontotemporal cortical degeneration of non-Alzheimer type (which included Pick''s disease). Several studies have documentated reduced concentration of somatostatin-LI in the brain and cerebrospinal fluid (CSF) in DAT. This study confirmed these results and showed in addition reduced CSF levels of somatostatin-LI in frontal lobe dementia (FTD), which has not been shown previously. There was no significant correlation with the duration of the disease. The histopathology and distribution of cortical degeneration in DAT and FTD differs in most aspects but shares the reduction in somatostatin-LI reduction. This suggests involvement of somatostatin neurons in these two types of primary degenerative dementias.
Parvalbumin Neurons in the Hippocampus in Senile Dementia of the Alzheimer Type, Parkinson's Disease and Multi-Infarct Dementia (Part 1 of 2)
Authors: Chan-Palay V.C. , Zetzsche T. , Höchli M.
Published: August 2007

The immunogold-silver-staining method (IGSS) was used for the detection of hippocampal neurons containing the cytoplasmic calcium-binding protein parvalbumin in senile dementia of the Alzheimer type (SDAT), Parkinson's disease and multi-infarct dementia (MID). Computer-based image analysis of cell numbers in the hippocampus proper and the entorhinal cortex, measurement of total dendritic length of selected neurons and quantitative microdensitometry of immunoreacted sections was performed. In severe SDAT cases a loss of parvalbumin-immunoreactive (parv-i) neurons and a reduction of dendritic fields was detected especially in CA1 and the subiculum. In the entorhinal cortex the general atrophy exceeded the decrease of parvalbumin immunoreactivity. Mild SDAT cases showed only minor alterations of parv-i neurons and in cases of parkinsonism without cognitive disorders or in those with depression parv-i neurons were not affected. However, in cases of parkinsonism with dementia and in MID a severe cell loss and a drastic reduction of dendritic arborization in the hippocampus proper was detected, which was accompanied by additional morphological alterations due to ischemic damage. We conclude that parv-i neuronal networks in the hippocampus are damaged in some patients with dementing disorders in SDAT, Parkinson's disease and MID consecutive to Alzheimer or ischemia related pathology.
Oral Tetrahydroaminoacridine Treatment of Alzheimer's Disease Evaluated Clinically and by Regional Cerebral Blood Flow and EEG
Authors: Minthon L. , Gustafson L. , Dalfelt G. , Hagberg B. , Nilsson K. , Risberg J. , Rosén I. , Seiving B. , Wendt P.E.
Published: August 2007

Neurochemical evidence indicates that cognitive impairment in dementia of Alzheimer type (DAT) is related to degeneration of cholinergic neurons in the brain. A pharmacological approach is treatment with a cholinesterase inhibitor such as tetrahydroaminoacridine (THA). THA treatment of 17 patients with DAT was studied with a double-blind crossover design with three types of treatment, THA + lecithin, THA + placebo and placebo + placebo. Each treatment period was 6 weeks with wash out periods of 2 weeks. The treatment was evaluated with clinical ratings, psychometric testing, EEG and regional cerebral blood flow (rCBF) measurements. No significant clinical differences between treatment periods were found in the total sample, but marked individual differences were observed. The patients were subdivided into three outcome groups based on four clinical measures: 6 patients improved (responders), 5 patients were mainly unchanged, and 6 patients showed further deterioration during the trial period of 26 weeks. Pretreatment rCBF in responders differed significantly from that of the deteriorated patients. EEG showed more high frequency activity among responders. Hepatotoxic side effects were observed in several cases. Three subjects showed marked increases of liver enzymes, with normalization following dose reduction. The majority of patients who improved or remained unchanged during the study chose to continue THA treatment in an open trial.
Increased Sweat Sodium Concentration in Patients with Alzheimer's Disease
Authors: Elmståhl Sölve , Winge Lennart
Published: August 2007

Sweat sodium concentration was estimated with pilocarpine iontophoresis in 15 women with Alzheimer''s disease (AD) and 29 healthy control women. The age ranged from 76 to 96 years with a mean age of 85 years in both groups. The mean sodium concentration of 91 ± 41 mmol/l (n = 11) in the Alzheimer patients was significantly higher than in the control group (62 ± 29 mmol/l, n = 27, p = 0.0011). 27% of AD patients and 7% of the control women did not respond to stimulation. The impaired sweating in AD patients make them more vulnerable to heat stress. Further studies are needed to reveal whether the neurophysiological mechanism involved is located in the hypothalamus, in cortical projections to the hypothalamus or in postganglionic sympathetic fibers.
Distribution of Iron in the Basal Ganglia and Neocortex in Postmortem Tissue in Parkinson's Disease and Alzheimer's Disease
Authors: Griffiths P.D. , Crossman A.R.
Published: August 2007

Post-mortem tissue was obtained from subjects with Parkinson's disease (PD), Alzheimer's disease (AD) and age-matched controls. Iron levels were measured from various sites of the basal ganglia and neocortex using atomic absorption spectrophotometry. The results indicate that iron levels are increased in the substantia nigra and the lateral segment of the globus pallidus of parkinsonian tissue. In contrast, the medial segment of the globus pallidus shows reduced iron levels in AD when compared to age-matched controls. No significant alterations of iron concentration were detected in AD in any region. These results are discussed in terms of the role of iron in the basal ganglia, mechanisms of abnormal deposition and possible neurotoxicity in PD.
Quantitative Assessment of the Synaptophysin Immuno-Reactivity of the Cortical Neuropil in Various Neurodegenerative Disorderswith Dementia
Authors: Zhan S.-S. , Beyreuther K. , Schmitt H.P.
Published: August 2007

It has remained a matter of debate until now whether amyloid and tangle pathology may be regarded as the main causes of the dementia in Alzheimer''s disease (AD) or only as markers of the disease. In the present study we examined the synaptophysin immunoreactivity of the cortical neuropil as a measure of its synapse density, in 17 cases of AD, 1 case with a 10-month episode of dementia and cortical amyloid deposition, 5 cases of Huntington''s disease (HD) with dementia, 11 cases of parkinsonism (PD), 5 with dementia (PD-D) and 16 controls. The immunoreactivity was assessed in two layers (molecular, pyramidal) of three regions (frontal, occipital, hippocampus) by means of automated black-and-white image analysis. In AD we found a rather diffuse reduction of the cortical synaptophysin expression of up to 26.5% (mean 11 %) of the controls. No correlation was found between synaptophysin expressivity and age either in AD or in the controls. Univariate analyses revealed only a very weak negative correlation between the density of βA4-immunoreactive cortical plaques and the intensity of the synaptophysin staining, while in a multivariate analysis the plaque density did not show any impact on the latter. In HD a reduction of the synaptophysin immunoreactivity of the cortical neuropil was also found (mean 10.4%), with a predominance in the pyramidal layer of the neocortex. The same was true for PD (5.3%) and PD-D (8.2%). Our results support the view that loss of synapses in the cortical neuropil may be a significant factor for the development of organic dementia, while the amyloid pathology in AD is more likely a marker of the disease.
Rare Neuropil Threads in Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia on Guam and in the Kii Peninsula of Japan
Authors: Wakayama Ikuro , Kihira Tameko , Yoshida Sohei , Garruto Ralph M.
Published: August 2007

Using three different silver impregnation methods and antisera against microtubule-associated protein-tau (MAP-tau) and amyloid β/A4 protein, we demonstrated abundant neurofibrillary tangles (NFTs), rare senile plaques, absence of amyloid angiopathy and rare MAP-tau- and silver-positive neuropil threads in the hippocampus of patients with amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) on Guam and in the Kii Peninsula of Japan. In contrast, abundant neuropil threads, NFTs, senile plaques with associated dystrophic neurites and amyloid angiopathy were confirmed in Alzheimer disease patients. These observations indicate that there may be important factor(s) responsible for the difference in the deposition and distribution of amyloid β/A4 protein and MAP-tau between Pacific ALS and PD and Alzheimer disease.
Frontal Lobe Degeneration of Non-Alzheimer Type Revisited
Authors: Brun Arne
Published: August 2007

The neuropathology of frontal lobe degeneration of non-Alzheimer type was reevaluated on the basis of a new material of 13 cases against the background of experiences from earlier published 16 cases. The salient neuropathological feature was an unspecific neuronal degeneration of superficial cortical layers of the frontal and to some extent the temporal lobes without markers for Alzheimer''s, Pick''s or Lewy body diseases and there were no indications so far of a prion etiology. The consistency of histopathological features are taken to indicate a disease entity, also identified by other authors. It is tentatively grouped together with progressive and aphasic dementia, similar cases in the literature and possibly also Pick''s disease and ALS with dementia.
Presenile Dementia with Motor Neuron Disease
Authors: Mitsuyama Yoshio
Published: August 2007

Seventy-one Japanese cases of presenile dementia with motor neuron disease were reviewed. The clinico-pathological features were: (1) progressive dementia with insidious onset, mostly in the presenile period: (2) neurogenic muscular wasting in the course of illness (ALS- or SPMA-like symptoms); (3) duration from the onset of the illness to death: 2-5 years (average 30.6 months); (4) extrapyramidal symptoms and definite sensory deficits are less commonly present; (5) no characteristic abnormalities in the CSF or EEG; (6) no known consanguinity or familial occurrence; (7) non-specific mild to moderate degenerative changes in the fronto-temporal cerebral cortex, hypoglossal nuclei and spinal cord, and frequently in the substantia nigra. The author was interested in discovering whether the frequency and topology of lesions in the brain of patients with presenile dementia and motor neuron disease differed characteristically from the distribution found in cases of Alzheimer''s disease, Pick''s disease, Creutzfeldt-Jakob disease or progressive subcortical gliosis. Presenile dementia with motor neuron disease might be a new disease entity.
Spectrum of Frontal Lobe Dementia in a Swedish Family
Authors: Passant Ulla , Gustafson Lars , Brun Arne
Published: August 2007

The etiology of frontal lobe dementia of non-Alzheimer type (FLD) is still unknown. There is strong evidence of genetic factors with positive heredity. In this paper, a Swedish family, with several generations affected by FLD is described. In 3 patients typical FLD was confirmed postmortem. The clinical and neuropathological similarities between the patients are impressive.
Exclusion Mapping in Familial Non-Specific Dementia
Authors: Brown Jeremy , Gydesen Susanne , Sorensen Sven Asger , Brun Arne , Duff Karen , Houlden Henry , Fidani Liana , Kullkarni Sunita , Cummings Juris , Goate Alison , Rossor Martin , Hardy John
Published: August 2007

We present genetic linkage data in a large family in which non-specific dementia is inherited as an autosomal dominant trait. We have analyzed 45 highly polymorphic microsatellite sequences and excluded a quarter of the genome as the site of the pathogenic mutation in this family.
Regional Cerebral Blood Flow in Frontal Lobe Dementia of Non-Alzheimer Type
Authors: Risberg Jarl , Passant Ulla , Warkentin Siegbert , Gustafson Lars
Published: August 2007

Twenty-five out of 26 cases of autopsy-verified frontal lobe degeneration of non-Alzheimer type (FLD) were found to have focal frontal or frontotemporal blood flow reductions involving both hemispheres. The deviant case had an asymmetric frontal pathology only apparent on the right side. Focal reduction of blood flow in the frontal lobes is, however, a common and unspecific flow abnormality found in e.g. Pick''s disease, Creutzfeldt-Jakob''s disease, and in some cases of Alzheimer''s disease. Low frontal flow has also been reported in schizophrenia and in toxic encephalopathy. Since a characteristic feature of FLD is a steady progress of the pathology, serial flow measurements extending over several years are especially informative.
Functional Imaging, the Frontal Lobes, and Dementia
Authors: Friedland Robert P. , Koss Elisabeth , Lerner Alan , Hedera Peter , Ellis William , Dronkers Nina , Ober Beth A. , Jagust William J.
Published: August 2007

A 58-year-old man developed progressive difficulty with comprehension and verbal output with dementia. Positron emission tomography with 18F 2-fluoro-2-deoxy-D-glucose demonstrated asymmetrical frontal and anterior temporal lobe loss of glucose use. Scopolamine infusion (0.3 mg) did not influence memory. Postmortem studies revealed evidence of Pick''s disease, with Pick bodies, loss of somatostatin, preservation of choline acetyltransferase and immunostaining with neurofilament antibodies. Pharmacological challenge and positron imaging offer valuable means for the noninvasive assessment of dementing illness. The contributions of functional imaging to our knowledge of frontal involvement in dementing illness are reviewed.
Progressive Right Frontotemporal Degeneration: Clinical, Neuropsychological and SPECT Characteristics
Authors: Miller Bruce L. , Chang Linda , Mena Ismael , Boone Kyle , Lesser Ira M.
Published: August 2007

The behavioral, neuropsychological and single photon emission computerized tomography characteristics of 5 patients with progressive degeneration of the right hemisphere are described. In all, the brain regions with greatest involvement were right-frontal and temporal. Psychosis, compulsions and behavioral disinhibition were the dominant, and often first, symptoms. Affect was flattened and the patients seemed distant and remote. Neuropsychological testing did not reveal a consistent pattern that helped localize the abnormality to the right frontotemporal region. These patients contrast dramatically to those with left frontotemporal degeneration in whom behavior and psychiatric status is often normal. This study suggests that the right hemisphere may be primary for the control of social conduct.
Assessment of Neuropsychological Dysfunction in Frontal Lobe Degeneration
Authors: Stuss Donald T.
Published: August 2007

The quality of the neuropsychological investigation of behavioural changes in frontal dementias is dependent on the specificity of the behavioural analyses. A review of methodological issues and published findings identifies possible potential reasons for misinterpretation of research neuropsychological data in these studies. The areas reviewed include the operational definitions of terms such as ''frontal lobes'' and ''frontal functions''; identification of experimental limitations in frontal lobe research; and highlights of neuropsychological investigations of frontal lobe functions. These deliberations suggest a practical approach to the behavioural assessment of frontal dementias.
Progressive Language Dysfunction and Lobar Atrophy
Authors: Snowden J.S. , Neary D.
Published: August 2007

The patterns of language disorder associated with ''progressive aphasia'' due to lobar atrophy were compared with the language dysfunction of patients with dementia of frontal lobe type (DFT). The progressive aphasias were characterised primarily by impairment at the structural levels of language: phonology, grammar and semantics, whereas DFT was associated primarily with aspontaneity and loss of generative capability. However, there was overlap in language symptomatology, particularly with progression of disease. The findings lend support to the argument that progressive aphasia and DFT represent different clinical manifestations of a common pathology, and form part of the spectrum of lobar atrophies.
Frontal Lobe Cognitive Functions in Aging: Methodologic Considerations
Authors: Brauer Boone Kyle , Miller Bruce L. , Lesser Ira M.
Published: August 2007

The empirical literature has been contradictory regarding whether frontal functions decline with age, perhaps due to important differences across studies in medical and psychiatric exclusion criteria. We review literature and present preliminary data suggesting that frontal lobe functions are particularly affected by several medical and psychiatric disorders common in old age. Investigations of frontal lobe functions in aging require careful screening of subject samples; otherwise, any impact of age on cognition is contaminated by the effects of coexistent physical and/or psychiatric illness.
The Ratio of Diffuse to Mature Beta/ A4 Deposits in Alzheimer's Disease Varies in Cases with and without Pronounced Congophilic Angiopathy
Authors: Armstrong R.A. , Myers D. , Smith C.U.M.
Published: August 2007

The density of diffuse, primitive, classic and compact Β/A4 deposits was estimated in the cortex and hippocampus in Alzheimer's disease (AD) cases with and without pronounced congophilic angiopathy (CA). The total density of Β/A4 deposits in a given brain region was similar in cases with and without CA. Significantly fewer diffuse deposits and more primitive/classic deposits were found in the cases with CA. The densities of the primitive, classic and compact deposits were positively correlated in the cases without CA. However, no correlations were observed between the density of the mature subtypes and the diffuse deposits in these cases. In the cases with CA, the density of the primitive deposits was positively correlated with the diffuse but not with the classic deposits. The data suggest that the mature Β/A4 deposits are derived from the diffuse deposits and that the presence of pronounced CA enhances their formation.
Induction of Memory and Cortical Cholinergic Neurochemical Recovery with Combine Fetal Transplantation and GM1 Treatments in Rats with Lesions of the NBM
Authors: Santucci Anthony C. , Gluck Renee , Kanof Philip D. , Haroutunian Vahram
Published: August 2007

Sixty-four Sprague-Dawley rats received ibotenic-acid-induced unilateral nucleus basalis of Meynert (nbM) lesions; 10 additional animals served as sham controls. Eight to ten days later, subjects with lesions received either fetal cholinergic transplants implanted within the ipsilateral (relative to the lesion) frontal cortex or control transplant surgeries. Lesioned animals with and without transplants were then treated with GM1 (20 mg/kg, i.p.) for either 0,1 or 10 days and were then trained and tested for 72-hour retention of passive avoidance. Results indicated that the lesion produced a significant impairment on this task. Transplant therapy combined with GM1 for 10 days yielded a significant reversal of this deficit. GM1 injections continued once per week for 4 weeks for half the lesioned animals in the transplant and no-transplant 10-day conditions. During a 6-month period, all subjects were assessed on two additional memory tasks (complex spatial discrimination and delayed spatial alternation). In general, there was no indication of a lesion, transplant, GM1, or transplant × GM1 effect on these tasks. Approximately 7.5 months after transplants, subjects were sacrificed and their frontal cortices examined for choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activity. Only lesioned subjects with transplants which were given sustained GMl treatment (i.e., 10 days plus weekly injections for 4 weeks) showed significant attenuations of lesion-induced CAT and AChE depletions. These data suggest that a combined treatment strategy of fetal transplant plus GM1 is capable of reversing nbM lesion-induced memory and neurochemical deficits in an animal model of the cholinergic deficits in Alzheimer's disease.
Influence of Feelings of Burden on the Caregiver's Perception of the Patient's Functional Status
Authors: Mangone C.A. , Sanguinetti R.M. , Baumann P.D. , Gonzalez R.C. , Pereyra S. , Bozzola F.G. , Gorelick P.B. , Sica R.E.P.
Published: August 2007

We studied the correlation between the caregiver's feelings of burden and the cognitive, behavioral and functional impairment of demented patients. We attempted to show the influence of caregiver's feelings of burden on their perception of the patients' functional status and to establish the predictors of feelings of burden. Twenty-five probable Alzheimer disease patients (NINCDS-ADRDA criteria) were assessed on cognitive measures and functional status (DAFS). The caregiver's index of burden (CIB), obtained from an adapted version of the Zarit Burden Interview, was correlated with the caregiver's report on the patient's instrumental activities of daily living (IADL) and physical self-maintenance functions (ADL); total and partial DAFS scores, and patient's cognitive and behavioral problems rated with the Functional Dementia Scale (FDS). The CIB correlated with the caregiver's report on the patient's behavioral disturbances (r = 0.71, p < 0.001) and physical self-maintenance activities (r = 0.62, p < 0.001), but not with cognitive impairment, IADL and the DAFS. The patients showed better functional performance in the direct assessment than in that reported by their caregivers (mainly in shopping, feeding, dressing, and ambulation). Thus, burden may foster a growing intolerance of the caregiver, inducing an underestimation of the patient's actual functional competence. The caregiver's report on the patient's behavioral problems was the best predictor of feelings of burden (F = 19,9, p < 0.001). We emphasized the utility of the DAFS for a more objective assessment of functional status, treatment of the patient's behavioral problems to lessen the caregiver's feeling of burden, and the assessment and control of the caregiver's burden to highlight the need for medical assistance or support groups.
Brain Perfusion Imaging in Parkinson's Disease and Alzheimer's Disease Demonstrated by Three-Dimehsional Surface Display with 123l-lodoamphetamine
Authors: Tachibana Hisao , Kawabata Keita , Tomino Yoshio , Sugita Minoru , Fukuchi Minoru
Published: August 2007

We reconstructed three-dimensional (3D) surface images from data from single-photon emission computed tomography (SPECT) with N-isopropyl-p[123I]-iodoamphetamine (123I-IMP) in 29 patients with Parkinson''s disease, 16 patients with Alzheimer''s disease and 11 normal control subjects. In patients with nondementing Parkinson''s disease, perfusion defects were frequently found in the parietal cortical region at a threshold value of 65%. In demented Parkinson''s disease patients, perfusion defects were frequently noted at threshold of 45–65 %, and were more marked in the bilateral temporal and parietal cortices. In Alzheimer''s disease, perfusion defects were similar to those found in dementing Parkinson''s disease. These results suggest that dementia in Parkinson''s disease is related to the perfusion reduction of the temporoparietal cortex, and may support the view that Parkinson''s disease and Alzheimer''s disease overlap in some patients. A 3D display of an 123I-IMP brain tomogram may be useful for detecting cortical lesions in patients with dementia or cognitive impairment.
Potential Biological Targets for Anti-Alzheimer Drugs
Authors: Allain H. , Belliard S. , de Certaines J. , Bentué-Ferrer D. , Bureau M. , Lacroix P.
Published: August 2007

The stunning accumulation of data on the physiopathology of Alzheimer''s disease is a real hindrance to pharmacologists who have to make decisions as to what molecules should be assessed first in man. Considering the cumbersomeness and cost of clinical trials in that field, a review of potential targets for drugs that are supposed to be active against the disease has become necessary, for a true definition of the rational justifications of trials to be envisaged.
Serial Angioscopic Evidence of Incomplete Neointimal Coverage After Sirolimus-Eluting Stent Implantation
Authors: Awata Masaki , Kotani Jun-ichi , Uematsu Masaaki , Morozumi Takakazu , Watanabe Tetsuya , Onishi Toshinari , Iida Osamu , Sera Fusako , Nanto Shinsuke , Hori Masatsugu , Nagata Seiki
Published: August 2007

Background—

The time course of neointimal formation after stent implantation has not been studied extensively by angioscopy in the drug-eluting stent era.

Methods and Results—

Serial angioscopic findings at first follow-up (3.6±1.1 months), second follow-up (10.5±1.6 months), and third follow-up (21.2±2.2 months) after stent implantation were compared between sirolimus-eluting stents (SES, n=17) and bare-metal stents (BMS, n=11). Neointimal coverage, thrombus, and presence of yellow plaques underneath the stents were assessed. Neointimal coverage was graded as follows: grade 0, stent struts were fully visible; grade 1, struts bulged into the lumen, although they were covered; grade 2, struts were embedded by the neointima but were seen translucently; or grade 3, struts were fully embedded and invisible. Neointimal coverage was remarkably different between SES and BMS at each follow-up point. Neointimal coverage grade was 1.1±0.5 in SES versus 2.9±0.3 in BMS at the first follow-up (
P
<0.0001), 1.1±0.5 in SES versus 3.0±0.0 in BMS (
P
<0.0001) at the second follow-up, and 1.3±0.5 in SES versus 3.0±0.0 in BMS at the third follow-up (
P
=0.0009). No significant serial changes in coverage grade were noted in the BMS group, whereas coverage grade slightly but significantly increased at the third follow-up in the SES group (
P
<0.05). Thrombi were detected in 4 SES: a red thrombus was seen from the first to the third follow-up in 2; another was detected only at the third follow-up; and the fourth was seen at the first follow-up but disappeared at the second follow-up, associated with a new white thrombus despite dual antiplatelet therapy. Yellow plaques had disappeared by the time of the second follow-up in BMS. In contrast, yellow plaques were exposed in 71% of SES at the first follow-up and remained exposed until the third follow-up. Neointimal coverage grades correlated with thrombi (
P
=0.002) and with yellow plaques (
P
<0.0001).

Conclusions—

Serial angioscopic findings up to 2 years after SES implantation were markedly different from those after BMS. Neointimal coverage was completed by 3 to 6 months in BMS. In contrast, SES demonstrated the presence of thrombi and yellow plaques even as much as 2 years after implantation.
Aortic Arch Atheroma Progression and Recurrent Vascular Events in Patients With Stroke or Transient Ischemic Attack
Authors: Sen Souvik , Hinderliter Alan , Sen Pranab K. , Simmons Jennifer , Beck James , Offenbacher Steven , Ohman E. Magnus , Oppenheimer Stephen M.
Published: August 2007

Background—

It is not known whether progression of aortic arch (AA) atheroma is associated with vascular events in patients with stroke or transient ischemic attack (TIA).

Methods and Results—

AA atheroma was detected on baseline transesophageal echocardiogram in 167 consecutive patients who had prevalent stroke or TIA. Of these, 125 consented to a follow-up transesophageal echocardiogram at 12 months. Adequate paired AA images were obtained in 117 (78 with strokes, 39 with TIAs), which allowed detailed measurements of plaques. On admission for their index stroke or TIA, patients were assessed for stroke risk factors, stroke subtypes, baseline AA plaque characteristics, and laboratory parameters. Progression of AA atheroma was observed in 33 patients (28%) on 12-month follow-up transesophageal echocardiogram. It was determined that the progression group had significantly higher adjusted homocysteine levels (
P
<0.0001) and neutrophil counts (
P
<0.0001) than the no-progression group. These patients were followed up for a median of 1.7 years from the index stroke/TIA (range 0.5 to 4.5 years) for vascular events including stroke, TIA, myocardial infarction, and death due to vascular causes. Kaplan-Meier curves showed fewer patients with AA atheroma progression remained free of the composite vascular end point (49% compared with 89% in the no-progression group;
P
<0.0001). AA atheroma progression was associated with composite vascular events (hazard ratio 5.8, 95% confidence interval 2.3 to 14.5,
P
=0.0002) after adjustment for a propensity score based on confounders.

Conclusions—

In this preliminary study of stroke/TIA patients with AA atheroma on transesophageal echocardiogram, AA atheroma progression was associated with recurrent vascular events.
How Sexist Is Aristotle's Developmental Biology?
Authors: Henry Devin
Published: August 2007

The aim of this paper is to evaluate the level of gender bias in Aristotle's Generation of Animals while exercising due care in the analysis of its arguments. I argue that while the GA theory is clearly sexist, the traditional interpretation fails to diagnose the problem correctly. The traditional interpretation focuses on three main sources of evidence: (1) Aristotle's claim that the female is, as it were, a "disabled" (πεπηρωμɛνo;ν) male; (2) the claim at GA IV.3, 767b6-8 that females are a departure from the kind; and (3) Aristotle's supposed claim at GA IV.3, 768a21-8 that the most ideal outcome of reproduction is a male offspring that perfectly resembles its father. I argue that each of these passages has either been misunderstood or misrepresented by commentators. In none of these places is Aristotle suggesting that females are imperfect members of the species or that they result from the failure to achieve some teleological goal. I defend the view that the GA does not see reproduction as occurring for the sake of producing males; rather, what sex an embryo happens to become is determined entirely by non-teleological forces operating through material necessity. This interpretation is consistent with Aristotle's view in GA II.5 that females have the same soul as the male (741a7) as well as the argument in Metaphysics X.9 that sexual difference is not part of the species form but is an affection (παoç) arising from the matter (1058b21-4). While the traditional interpretation has tended to exaggerate the level of sexism in Aristotle's developmental biology, the GA is by no means free of gender bias as some recent scholarship has claimed. In the final section of the paper I point to one passage where Aristotle clearly falls back on sexist assumptions in order to answer the difficult question, "Why are animals divided into sexes?". I argue that this passage in particular poses a serious challenge to anyone attempting to absolve Aristotle's developmental biology of the charge of sexism.
Dirtying Aristotle's Hands? Aristotle's Analysis of 'Mixed Acts' in the Nicomachean Ethics III, 1
Authors: Nielsen Karen
Published: August 2007

The analysis of 'mixed acts' in Nicomachean Ethics III, 1 has led scholars to attribute a theory of 'dirty hands' and 'impossible oughts' to Aristotle. Michael Stocker argues that Aristotle recognizes particular acts that are simultaneously 'right, even obligatory', but nevertheless 'wrong, shameful and the like'. And Martha Nussbaum commends Aristotle for not sympathizing 'with those who, in politics or in private affairs, would so shrink from blame and from unacceptable action that they would be unable to take a necessary decision for the best'. In this paper I reexamine Aristotle's analysis of putatively 'mixed acts' in Nicomachean Ethics III, 1, maintaining that Aristotle denies that there are acts that are (i) voluntary under the circumstances, (ii) right, all things considered, under the circumstances, but nevertheless (iii) shameful or wrong for moral or prudential reasons under the circumstances. The paper defends this interpretation with reference to Aristotle's discussion of shame in EN IV, 9 and Rhetoric II, 6, as well as his overall meta-ethical commitment to a position I call 'mitigated circumstantial relativism'. By focusing on Aristotle's analysis of putatively 'mixed acts', we come closer to a true appreciation of Aristotle's ethical theory, even though 'mixed act' is not, I argue, a category in Aristotle's considered ontology of action.
Conditioned reinforcement in the crayfish Orconectes rusticus
Authors: Hazlett Brian
Published: August 2007

The crayfish Orconectes rusticus can form a learned association between alarm odour (an unlearned signal of elevated predation risk) and a formerly neutral odour. In this study the odours of gyrinid beetles and of the snail Campeloma decisum were each paired with alarm odour and subsequently those odours significantly reduced feeding behaviours in the presence of food odour. To test for second-order (=conditioned) reinforcement, crayfish were first exposed simultaneously to one of the neutral odours and alarm odour and later exposed simultaneously to the two formerly neutral odours. When tested with the second neutral odour (which was not paired with alarm odour) the crayfish showed significant reductions in food-related behaviours, thus demonstrating second-order conditioning.