bluuebunny/crossref_metadata_2025 huggingface dataset:
Statin therapy, alone or with rapamycin, does not reverse monocrotaline pulmonary arterial hypertension: the rapamcyin-atorvastatin-simvastatin study
Authors: McMurtry M. Sean , Bonnet Sebastien , Michelakis Evangelos D. , Bonnet Sandra , Haromy Alois , Archer Stephen L.
Published: August 2007

Pulmonary arterial hypertension (PAH) is characterized by excessive pulmonary artery smooth muscle cell proliferation and impaired apoptosis leading to obstruction of resistance pulmonary arteries. We hypothesized that antiproliferative (rapamycin) and proapoptotic (statins) agents, already used clinically for other indications, would decrease experimental PAH, facilitating translation to human therapies. Prior studies in the rat monocrotaline-PAH model have indicated that simvastatin regresses and rapamycin prevents, but cannot reverse, PAH. Two PAH regression strategies (rapamycin monotherapy vs. rapamycin + atorvastatin) and one prevention strategy (simvastatin) were tested in a rat monocrotaline-PAH model. Adult male Sprague-Dawley rats were randomized to saline ( n = 6) or monocrotaline (60 mg/kg ip, n = 36) treatment groups. Monocrotaline rats were randomized to gavage with vehicle, rapamycin (2.5 mg·kg−1·day−1), or rapamycin + atorvastatin (10 mg·kg−1·day−1) treatment groups, beginning 12 days post-monocrotaline. Echocardiographic and hemodynamic end points were assessed 2 wk later. Additional monocrotaline-PAH rats ( n = 20) were randomized to vehicle or simvastatin (2 mg·kg−1·day−1) treatment groups and followed echocardiographically for 4 wk. Monocrotaline-PAH increased lung p70 S6 kinase phosphorylation, and this was reversed by rapamycin, confirming the biological activity of rapamycin. Despite the use of high doses, neither rapamcyin nor rapamycin + atorvastatin improved survival nor reduced PAH, vascular remodeling, and right ventricular hypertrophy. Although prophylactic simvastatin slowed PAH progression, by 4 wk PAH severity and mortality were not different from placebo. Apart from the new finding of p70 S6 kinase phosphorylation in monocrotaline-PAH, this is a negative therapeutic trial (none of these promising therapies improved monocrotaline-PAH). These negative results should be considered as human trials with these agents are underway (simvastatin) or proposed (rapamycin).
Past and present course of cardioprotection against ischemia- reperfusion injury
Authors: Liem David A. , Honda Henry M. , Zhang Jun , Woo David , Ping Peipei
Published: August 2007

Despite tremendous advances in cardiovascular research and clinical therapy, ischemic heart disease remains the leading cause of serious morbidity and mortality in western society and is growing in developing countries. For the past 5 decades, many scientists have studied the pathophysiology of myocardial ischemia-reperfusion (I/R) injury leading to infarction. With the exception of reperfusion therapy, attempts to salvage the myocardium during an acute myocardial infarction showed disappointing results in directly decreasing infarct size. Nevertheless, the phenomena of ischemic preconditioning and ischemic postconditioning show a consistent and robust cardioprotective effect in every used experimental animal model. As a result, many studies have focused on the intracellular protective signaling pathways that are involved in preconditioning and postconditioning. More recently, it has been suggested that components of the reperfusion injury salvage kinases pathway, protein kinase B, and the extracellular signal-regulated kinases can induce cardioprotection against I/R injury when they are activated during the postischemic reperfusion period. In addition, inhibition of mitochondrial permeability transition during postischemic reperfusion also shows a strong cardioprotective effect against I/R injury. The present mini-review highlights a short summary of the historical and present course of research into cardioprotection against myocardial I/R injury.
Stress and Wound Healing
Authors: Christian Lisa M. , Graham Jennifer E. , Padgett David A. , Glaser Ronald , Kiecolt-Glaser Janice K.
Published: August 2007

Over the past decade it has become clear that stress can significantly slow wound healing: stressors ranging in magnitude and duration impair healing in humans and animals. For example, in humans, the chronic stress of caregiving as well as the relatively brief stress of academic examinations impedes healing. Similarly, restraint stress slows healing in mice. The interactive effects of glucocorticoids (e.g. cortisol and corticosterone) and proinflammatory cytokines [e.g. interleukin-1β (IL-1β), IL-1α, IL-6, IL-8, and tumor necrosis factor-α] are primary physiological mechanisms underlying the stress and healing connection. The effects of stress on healing have important implications in the context of surgery and naturally occurring wounds, particularly among at-risk and chronically ill populations. In research with clinical populations, greater attention to measurement of health behaviors is needed to better separate behavioral versus direct physiological effects of stress on healing. Recent evidence suggests that interventions designed to reduce stress and its concomitants (e.g., exercise, social support) can prevent stress-induced impairments in healing. Moreover, specific physiological mechanisms are associated with certain types of interventions. In future research, an increased focus on mechanisms will help to more clearly elucidate pathways linking stress and healing processes.
Bidirectional Communication between the Brain and the Immune System: Implications for Physiological Sleep and Disorders with Disrupted Sleep
Authors: Lorton Dianne , Lubahn Cheri L. , Estus Chris , Millar Brooke A. , Carter Jeffery L. , Wood Carlo A. , Bellinger Denise L.
Published: August 2007

This review describes mechanisms of immune-to-brain and brain-to-immune signaling involved in mediating physiological sleep and altered sleep with disease. The central nervous system (CNS) modulates immune function by signaling target cells of the immune system through autonomic and neuroendocrine pathways. Neurotransmitters and hormones produced and released by these pathways interact with immune cells to alter immune functions, including cytokine production. Cytokines produced by cells of the immune and nervous systems regulate sleep. Cytokines released by immune cells, particularly interleukin-1β and tumor necrosis factor-α, signal neuroendocrine, autonomic, limbic and cortical areas of the CNS to affect neural activity and modify behaviors (including sleep), hormone release and autonomic function. In this manner, immune cells function as a sense organ, informing the CNS of peripheral events related to infection and injury. Equally important, homeostatic mechanisms, involving all levels of the neuroaxis, are needed, not only to turn off the immune response after a pathogen is cleared or tissue repair is completed, but also to restore and regulate natural diurnal fluctuations in cytokine production and sleep. The immune system’s ability to affect behavior has important implications for understanding normal and pathological sleep. Sleep disorders are commonly associated with chronic inflammatory diseases and chronic age- or stress-related disorders. The best studied are rheumatoid arthritis, fibromyalgia and chronic fatigue syndromes. This article reviews our current understanding of neuroimmune interactions in normal sleep and sleep deprivation, and the influence of these interactions on selected disorders characterized by pathological sleep.
Specificity of Temporal Amygdala Atrophy in Alzheimer’s Disease: Quantitative Assessment with Magnetic Resonance Imaging
Authors: Maunoury Christophe , Michot Jean-Luc , Caillet Hubert , Parlato Vincenzo , Leroy-Willig Anne , Jehenson Philippe , Syrota André , Boller François
Published: August 2007

The aim of the study was to assess the specificity of temporal amygdala (TA) atrophy with magnetic resonance imaging (MRI) by comparing a group of early impaired patients with Alzheimer''s disease (AD) with ''other types of dementia'' and controls. In this prospective case-control study, 41 patients were selected: 12 with probable AD according to NINCDS-ADRDA and CERAD inclusion and exclusion criteria, 14 with other types of dementia and 15 age-matched control subjects. Two radiologists blindly measured the TA volumes on coronal oblique contiguous slices with a 1.5-tesla MRI Scanner. TA volume measurements obtained by the 2 observers and right-left TA values were not significantly different. A significant TA atrophy was found in the AD group as compared to the other groups, with 39.7% (p < 0.001) difference in TA volumes between AD and other types of dementia groups and 41.4% (p < 0.0005) difference between AD and control groups. There was no significant difference between other types of dementia and control groups. There was an overlap between the three groups for 4 patients. TA atrophy assessed with MRI could be of diagnostic value in AD, especially in the early stage of the disease.
Comparative Study of Aprosody in Alzheimer's Disease and in Multi-lnfarct Dementia
Authors: Pérez Trullen J.M. , Modrego Pardo P.L
Published: August 2007

Prosody is defined as the melodic line of language. In this study we included 25 patients with probable Alzheimer''s disease and 14 with multi-infarct dementia for a comparative cross-sectional study of prosody. Neuropsychological analysis was based on Mini-Mental test, Blessed Scale and Clinical Dementia Rating. We used the criteria of Monrad-Krohn to evaluate prosodic categories. We found intrinsic aprosody in 8 patients with Alzheimer''s disease and in none of the patients with multi-infarct dementia (prevalence ratio: 1.82, 95% CI: 1.32–2.51), and emotional aprosody in 17 patients with Alzheimer''s disease in comparison to 4 with multi-infarct dementia (prevalence ratio: 1.8, 95% CI: 1.04–3.18). The differences in intellectual and inarticulate aprosody were not significant. We conclude that aprosody is more frequent and severe in Alzheimer''s disease than in multi-infarct dementia.
Pattern Visual Evoked Potential Mapping in Alzheimers Disease Correlations with Visuospatial Impairment
Authors: Martinelli Vittorio , Locatelli Tiziana , Comi Giancarlo , Lia Chiara , Alberoni Margherita , Bressi Sergio , Rovaris Marco , Franceschi Massimo , Canal Nicola
Published: August 2007

We evaluated pattern visual evoked potentials (PVEPs) in patients with Alzheimers disease (AD) and correlated the neurophysiological results with visuospatial performances in order to understand better the underlying causes of visual disturbances. Latencies and topographical distribution of PVEP components were evaluated in 20 AD patients who underwent an extensive battery of neuropsychological tests. Mean latencies of N70 and P100 were normal in AD patients, while mean latencies of N140 and P200 were significantly increased in comparison with age-matched healthy controls. The topographical distribution of PVEP components did not show any signiflcant difference between the two groups. Visuospatial impairment was detected in 8 patients (40%). Statistically significant positive correlations were observed between P200 amplitude (posterior right hemisphere mean z score) and performance in visuospatial tests. Our data are consistent with a sparing of foveal retinocortical pathways and with the selective dysfunction of either cortico-cortical connections between the striate cortex and the visual associative structures or of right temporo-parieto-occipital visual analyzers.
The Spatial Pattern of Discrete β-Amyloid Deposits in Alzheimers Disease Reflects Synaptic Disconnection
Authors: Armstrong R.A.
Published: August 2007

The spatial pattern of discrete β-amyloid (Aβ) deposits was studied in the superficial laminae of cortical fields of different types and in the hippocampus in 6 cases of Alzheimer''s disease (AD). In 41/42 tissues examined, discrete Aβ deposits were aggregated into clusters and in 34/41 tissues (25/34 of the cortical tissues), there was evidence for a regular periodicity of the Aβ deposit clusters parallel to the tissue boundary. The dimensions of the clusters varied from 400 to > 12,800 µm in different tissues. Although the Aβ deposit clusters were larger than predicted, the regular periodicity suggests that they develop in relation to groups of cells associated with specific projections. This would be consistent with the hypothesis that the distribution of discrete Aβ deposits in AD could reflect progressive synaptic disconnection along interconnected neuronal pathways. This implies that amyloid deposition could be a response to, rather than a cause of, synaptic disconnection in AD.
Isolated Amnesia with Slow Onset and Stable Course, without Ensuing Dementia: MRI and PET Data and a Six-Year Neuropsychological Follow-Up
Authors: Miceli G. , Colosimo C. , Daniele A. , Marra C. , Perani D. , Fazio F.
Published: August 2007

Patient EDS presented with an amnesic disorder of insidious onset (4 years) that remained stable and restricted to memory functions over a 10-year course. Repeated neuropsychological evaluations over 6 years showed a moderate-to-severe, stable impairment of long-term memory and of memory for public events, and a milder, stable impairment of autobiographic memory and of short-term memory. Language, perception, praxis and ''frontal'' functions were fully preserved. MRI showed atrophy of the right hippocampus, of the right mammillary body and of the sylvian fissure (bilaterally, but more marked on the left). On PET scan, metabolic activity in the mesial temporal structures was significantly reduced on the right and was at lower normal levels on the left. The disorder observed in EDS is similar to that recently reported in other patients. Possible etiologies of the selective amnesia observed in EDS are considered and their implications discussed.
Cortical Synaptic Changes and Gliosis in Normal Aging, Alzheimer's Disease and Frontal Lobe Degeneration
Authors: Liu Xiaoying , Erikson Catarina , Brun Arne
Published: August 2007

The most important new development during recent years in the field of degenerative dementia concerns synaptic pathology. So far it has been investigated in some regions and some cortical laminae in Alzheimer''s disease (AD). The present communication is a more comprehensive study of all laminae in four different regions, the prefrontal, parietal, inferior temporal and posterior cingulate cortex. Against the background of normal aging, AD was compared with another degenerative disorder, frontal lobe degeneration of non-Alzheimer type (FLD). The synapse density was measured using synaptophysin as a marker. Astrocytes were also counted in the molecular layer. In normals, the cortex showed successively lower synaptic density from layer I to layer VI and relatively lowest density in the prefrontal cortex and a general decline with increasing age. A 46-49% decrease in synaptic density was found in all laminae in all regions of AD brains, a finding different from that in FLD. The number of astrocytes increased significantly in the prefrontal cortex both in AD and FLD but parietally only in AD. These results contribute to the understanding of normal synaptic organization of cortex, demonstrate the laminar and regional distribution of synaptic loss in AD and underscore the difference between AD and FLD. The gliosis appears to be secondary to the neurodegenerative changes. Synaptic loss is likely to be a common pathogenetic feature of neurodegenerative disorders and a likely cause of clinical symptoms and regional metabolic decrements in dementia.
An Atypical Neuroleptic Drug in the Treatment of Behavioural Disturbances and Psychotic Symptoms in Elderly People
Authors: Robertsson B. , Karlsson I. , Eriksson L. , Olsson J.-O. , Olofsson H. , Jacobsson N.O. , Årnell G.
Published: August 2007

The present study is a retrospective study of remoxipride therapy. A total of 103 patients, 65 years or older, with a DSM-III-R diagnosis of dementia or delirium, were included. They had all been treated with remoxipride because of psychotic symptoms or behavioural disturbances. The dose range of remoxipride was 50-300 mg, the median dose being 75 mg. The clinical effect was rated as good in two thirds of the patients, and side-effects were noted in one fourth. When psychomotor hyperactivity was the dominating problem, a good effect was rated in 81 % of the patients. Side-effects were few and mild, the most common being tiredness; only 5 patients showed extrapyramidal symptoms.
Apolipoprotein E Genotype in the Prediction of Cognitive Decline and Dementia in a Prospectively Studied Elderly Population
Authors: Brayne C. , Harrington C.R. , Wischik C.M. , Huppert F.A. , Chi L.Y. , Xuereb J.H. , O'Connor D.W. , Paykel E.S.
Published: August 2007

An increased apolipoprotein E (ApoE) type Ε4 allele frequency is associated with both sporadic and familial late-onset Alzheimer''s disease (AD). The age of onset of disease in patients homozygous for the Ε4 allele appears to be decreased by approximately 15 years compared with E2/3 individuals. In order to assess the influence of this allele on both dementia and cognitive decline in the elderly we have determined the ApoE genotype of 150 individuals over the age of 75 years who have taken part in a longitudinal study. Homozygosity for the Ε4 allele was rare. Of the 2 homozygotes, 1 was severely demented but the other did not receive a clinical diagnosis of dementia. The latter individual did demonstrate marked cognitive decline over a 28-month period. There was a consistent association between the presence of an Ε4 allele and both the clinical diagnosis of dementia and cognitive decline. These findings confirm a genetic heterogeneity in late-onset sporadic AD and prompt caution in the use of ApoE genotype to predict an elderly individual''s susceptibility to either dementia or cognitive decline.
A Pilot Study of Prednisone in Alzheimer's Disease
Authors: Aisen Paul , Marin Deborah , Altstiel Larry , Goodwin Catherine , Baruch Bella , Jacobson Rachel , Ryan Theresa , Davis Kenneth L.
Published: August 2007

Prelimininary to a multicenter trial, an open-label pilot study was conducted of prednisone treatment in Alzheimer''s disease. Prednisone was given at an initial dose of 10 mg (part 1) or 20 mg (part 2) and tapered over 7 weeks. There were no serious adverse events attributed to the medication, and there were no significant changes in either mean cognitive or behavioral assessment scores with treatment during either part. Serum levels of the acute phase proteins α-1-antichymotrypsin and C-reactive protein did not change significantly during part 1, but were suppressed by the higher dose given in part 2. Thus, a prednisone regimen with an initial dose of 20 mg is tolerable and results in suppression of the acute phase response in Alzheimer''s disease.
The Use of Multivariate Methods in the Identification of Subtypes of Alzheimer's Disease: A Comparison of Principal Components and Cluster Analysis
Authors: Armstrong R.A. , Wood L. , Myers D. , Smith C.U.M.
Published: August 2007

Two contrasting multivariate statistical methods, viz., principal components analysis (PCA) and cluster analysis were applied to the study of neuropathological variations between cases of Alzheimer''s disease (AD). To compare the two methods, 78 cases of AD were analysed, each characterised by measurements of 47 neuropathological variables. Both methods of analysis revealed significant variations between AD cases. These variations were related primarily to differences in the distribution and abundance of senile plaques (SP) and neurofibrillary tangles (NFT) in the brain. Cluster analysis classified the majority of AD cases into five groups which could represent subtypes of AD. However, PCA suggested that variation between cases was more continuous with no distinct subtypes. Hence, PCA may be a more appropriate method than cluster analysis in the study of neuropathological variations between AD cases.
Cerebral Metabolic Changes in Alzheimer's Disease: Neurobehavioral Patterns
Authors: Blesa Rafael , Mohr Erich , Miletich Robert , Hildebrand Kathleen , Sampson Margaret , Chase Thomas N.
Published: August 2007

Regional cerebral glucose metabolism was surveyed in 37 Alzheimer''s disease (AD) patients and 21 normal controls using positron emission tomography. Where possible, brain regions were specified according to their neurobehavioral function rather than as anatomically demarcated structures. Absolute metabolic values revealed significant differences (p < 0.05) between AD patients and controls for whole brain and the more superior supratentorial brain slices. Normalized values (region/brain stem) showed the most striking declines (p < 0.001) in the association cortex (heteromodal region -21%; unimodal region -19%) and the primary sensory-motor cortex (-13%), with motor, auditory, and visual areas more affected than somatosensory areas. Limbic and para-limbic systems were equally affected (-14%; -11%; p < 0.001). Thalamus, striatum, cerebellum and brain stem were minimally or not affected. Neurobehaviorally defined hypometabolic regions largely parallel affected areas noted in anatomic and previous metabolic studies, with the possible exception of metabolic deficits in the primary sensory-motor complex. Conceivably, brain areas unaffected morphologically by the pathophysiological processes of AD may become dysfunctional due to a disruption of connectivity between regions.
The Enhancing Effect of Pyridostigmine on the GH Response to GHRH Undergoes an Accelerated Age-Related Reduction in Down Syndrome
Authors: Arvat E. , Gianotti L. , Ragusa L. , Valetto M.R. , Cappa M. , Aimaretti G. , Ramunni J. , Grottoli S. , Camanni F. , Ghigo E.
Published: August 2007

Cholinergic agonists are known to potentiate GHRH-induced GH secretion, probably acting via inhibition of hypothalamic somatostatin release. Their effect is reduced in aging and in patients with Alzheimer''s disease. This may be the consequence of age-related cholinergic impairment, which, in turn, could cause somatostatinergic hyperactivity leading to GH hyposecretion. As in Down syndrome (DS) neural alterations have been reported similar to those in aging, including cholinergic impairment, we verified the GH response to GHRH (1 µg/kg i.v. at 0 min) alone or combined with pyridostigmine (PD), a cholinesterase inhibitor (60 and 120 mg, respectively, in children and adults, orally at –60 min) in 15 DS children (13.5 ± 0.6 years) and in 11 DS young adults (24.0 ± 1.2 years). Fifteen normal children (11.9 ± 0.5 years), 15 normal adults (27.3 ± 0.9 years) and 16 normal elderly (76.3 ±1.5 years) were studied as controls. IGF-I levels showed an age-related reduction both in DS (children vs. adults, mean ± SEM: 354.8 ± 44.9 vs. 204.4 ± 29.4 µg/1, p<0.02) and in controls (normal children vs. normal adults vs. normal elderly: 281.4 ± 36.3 vs. 175.4 ± 11.2 vs. 72.5 ± 6.6 µg/1, p< 0.001). The GH response to GHRH in DS children was higher than in DS adults (areas under curve: 1,197.6 ± 241.5 vs. 434.4 ± 83.3 µg/l/h, p< 0.01). On the other hand, in normal subjects the GHRH-induced GH rise was similar in children and adults (1,056.2 ± 128.4 vs. 800.8 ± 124.5 µg/l/h) and both were higher than that in elderly subjects (296.0 ± 61.0 µg/l/h, p< 0.001).PD enhanced the GH response to GHRH both in DS and in normal subjects (p < 0.005). The GH response to PD+GHRH was lower in DS adults than in DS children (1,068.1 ± 145.7 vs. 1,897.4 ± 198.8 µg/I/h, p < 0.001) as well as in normal elderly subjects with respect to that in normal children and normal adults (832.3 ± 144.7 vs. 2,172.1 ± 156.1 and 2,347.6 1 322.4 µg/l/h, respectively, p < 0.001). The GH response to GHRH alone or combined with PD in DS adults was lower (p < 0.01) than that in normal adults and similar to that in normal elderly subjects. In conclusion, the present data demonstrate that the stimulated GH secretion in DS undergoes an accelerated age-related reduction. They also suggest the existence of a precocious impairment of central cholinergic activity in DS, which, in turn, could cause somatostatinergic hyperactivity and reduced GH secretion.
Elevated Alpha1-Antichymotrypsin Serum Levels in a Subset of Nondemented First-Degree Relatives of Alzheimer's Disease Patients
Authors: Altstiel Larry D. , Lawlor Brian , Mohs Richard , Schmeidler James , Dalton Arthur , Mehta Pankesh , Davis Kenneth
Published: August 2007

A portion of Alzheimer''s disease (AD) patients have elevated serum levels of the acute phase reactant α1-antichymotrypsin (A1ACT) compared to age-matched controls. We measured serum levels of A1ACT in AD patients, age-matched controls, Down''s Syndrome patients, and nondemented first-degree relatives of AD patients. Significantly elevated levels of A1ACT were found in both AD patients and first-degree-relatives. In AD patients, serum A1ACT concentrations decreased with increasing severity of cognitive impairment. These results may suggest that inflammatory phenomena may be an early component of AD pathophysiology.
Chronic Obstructive Pulmonary Disease and Associated Patterns of Memory Decline
Authors: Fioravanti Mario , Nacca Daniele , Amati Stefano , Buckley Ann E. , Bisetti Alberto
Published: August 2007

The relationship between chronic obstructive pulmonary disease (COPD) and cognitive functioning was analyzed in a study with 50 aging patients. A complex pattern of interactions was identified between emotional and cognitive functioning and chronic respiratory disease when the effects of age, sex, type and severity of disease were controlled. These patients did not show any global and diffuse cognitive impairment. Only a portion of COPD patients (about 30%) evidenced memory impairment which was confined to immediate memory. Memory impairment found in these patients did not appear to be associated with those changes present in the aging process but was mainly related to those specific clinical and instrumental parameters which are considered valid indicators of respiratory efficiency. Two types of cognitive and emotional problems were identified. A progressive stage-dependent set of characteristics was associated with the course of the disease and a fluctuating, probably reversible state-dependent set of characteristics was associated with the temporary condition of the patients during the period of examination. Patients who had received more recent medical treatment or who were under protection of vaccination for influenza showed a better cognitive and emotional efficiency.
Education and Occupation as Risk Factors for Dementias of the Alzheimer and Ischemic Vascular Types
Authors: Mortel Karl F. , Meyer John Stirling , Herod Brian , Thornby John
Published: August 2007

Education and occupation as sociodemographic risk factors for dementias of the Alzheimer (DAT) and ischemic vascular types (IVD) were evaluated by two case series studies. Cases were compared to well-evaluated individuals identified as healthy normals acting as controls. There were 150 patients with probable DAT, 102 patients with probable IVD, and 188 neurologically and cognitively normal subjects. Logistic regression indicated that for DAT, education with occupation was the best predictor (OR, 1.51; 95% CI, 1.23–1.87). For IVD, the two predictors were: education with occupation (OR, 1.84; 95% CI 1.38–4.50) and education with gender (OR, 3.40; 95% CI, 1.29–8.92). We conclude that risk of dementia is increased in those with limited educational background and occupational achievement.
Delusional Misidentification and Subsequent Dementia: A Clinical and Neuropathological Study
Authors: Diesfeldt H.F.A. , Troost D.
Published: August 2007

An 81-year-old man presented with psychotic episodes involving the delusion that his wife had been replaced by a closely resembling double (the so-called Capgras delusion). A comprehensive neuropsychological investigation revealed no signs of dementia at that time, but in the subsequent course the patient became demented and died 5 years later. Neuropathological and neurochemical examination displayed many diffuse plaques in the cortex that escaped detection by Congo-red but were clearly demonstrated by antibodies raised to β-amyloid protein. Neurofibrillary tangles were absent in the cortex. Antiubiquitin immunohistochemistry revealed some cortical and subcortical Lewy bodies. The hippocampus and the majority of the nigral cells were intact. However, in the frontal and parietal white-matter many small Iacunar infarcts were found due to arteriosclerotic and hypertensive vessel wall changes. Though the etiology of psychotic symptoms in the context of dementia is complex, this study shows the possible significance of white-matter lesions in the pathogenesis of delusions and subsequent dementia.
Long-Term Estrogen Replacement Therapy in Female Patients with Dementia of the Alzheimer Type: 7 Case Reports
Authors: Ohkura Takeyoshi , Isse Kunihiro , Akazawa Kenji , Hamamoto Makoto , Yaoi Yoshimasa , Hagino Nobuyoshi
Published: August 2007

Seven female patients with mild to moderate dementia of the Alzheimer type (DAT) were treated with long-term, low-dose estrogen replacement therapy (ERT) over a period of 5–45 months. Five of the 7 patients were cases who had responded well to short-term ERT with 1.25 mg/day of conjugated equine estrogens (CEE) for 6 weeks. The 7 patients from 56 to 77 years of age received 0.625 mg/day of CEE for 21 days, followed by a pause of 7 days. A28-day cycle of low-dose ERT was performed repeatedly. In 4 cases, these patients received 5 mg/day of medroxyprogesterone acetate (MPA) during the last 10–12 days of estrogen treatment. Therapeutic efficacy of estrogen was evaluated by psychometric assessments such as the Mini-Mental State Examination (MMSE) and the Hasegawa Dementia Scale (HDS) and a behavior rating scale of the Gottfries-Bråne-Steen geriatric rating scale (GBS). The MMSE and HDS evaluations were performed principally once in 2–4 weeks. In 4 out of the 7 patients, the MMSE and HDS scores were elevated above the pretreatment levels during ERT. The termination of ERT resulted in a decrease in both scores. Furthermore, the GBS scores and daily activities of the same 4 patients were improved during ERT. In these 4 patients cognitive functions were markedly improved throughout the treatment period, while the other 2 patients responded moderately well and another patient did not respond at all. These observations suggest that long-term, low-dose ERT improves cognitive functions, dementia symptoms and daily activities in women with mild to moderate DAT. However, the supplemental treatment with MPA seems to have an unfavorable effect on dementia symptoms and daily activities in the aged DAT patients.
Visual Memory in Alzheimer Patients: Effects of Practice, Retention Interval and Severity of Cognitive Decline
Authors: Heun Reinhard , Bierbrauer Jürgen , Benkert Otto
Published: August 2007

The study was aimed at estimating the effect size of practice, retention interval and dementia severity on free recall performance in Alzheimer patients. Patients met DSM-III-R criteria for dementia of Alzheimer type. Different picture sets were presented on 4 days. The forgetting curves on different days were compared using ANOVA for repeated measurements. Practice had a minor, but significant negative effect on recall performance explaining 1% of the variance in recall performance. The retention interval varied between zero and 24 h explaining 23% of the total variance. Dementia severity explained 52% of the variance. For the development of memory improvement strategies in Alzheimer patients, the repeated measurement design using intraindividual comparisons seems more powerful than group comparisons.
Neuronal Number and Size Are Preserved in the Nucleus basalis of Aged Rhesus Monkeys
Authors: Voytko Mary Lou , Sukhov Renat R. , Walker Lary C. , Breckler Steven J. , Price Donald L. , Koliatsos Vassilis E.
Published: August 2007

Neurons in the nucleus basalis of Meynert (NBM) were analyzed morphometrically in 21 rhesus monkeys ranging in age from 9 to 33 years. Numbers of cholinergic neurons were similar across all ages at several NBM levels in either Nissl-stained paraffin sections or sections processed immunocytochemically for nerve growth factor receptor (p75LNGFr) Size of NBM neurons was larger in aged monkeys than young monkeys at all NBM levels, particularly in the most posterior subdivision. A subset of monkeys were behaviorally characterized shortly before death, and partial correlation analyses indicated that increased age was associated with declines in recognition memory, visuospatial orientation, and reaction time. Controlling for age, spatial memory and concurrent discrimination abilities were associated with lower cell number in intermediate NBM. Numbers of neurons in anterior NBM did not correlate with any behavioral measure. These observations indicate that numbers of NBM cholinergic neurons are stable with age, that NBM neurons become hypertrophic in older animals, and that morphometric indices of cholinergic neurons are associated with cognitive function.
The Cortical Neuritic Dystrophy of Alzheimer’s Disease: Nature, Significance, and Possible Pathogenesis
Authors: Larner Andrew J.
Published: August 2007

It has been increasingly appreciated in the last decade that the neocortex of the Alzheimer’s disease brain is characterized by a widespread neuritic dystrophy, spatially distinct from that observed surrounding neuritic amyloid plaques. The nature and significance of this cortical neuritic dystrophy and its possible pathogenesis are the topics of this review. It may represent a regenerative sprouting response of neurons to partial deafferentation following cell loss; alternatively it may reflect a primary aberrant growth phenomenon leading to cell loss. Such changes could result from derangement of neurite growth-promoting and growth-inhibitory factors in the Alzheimer’s disease brain.
THA – Historical Aspects, Review of Pharmacological Properties and Therapeutic Effects
Authors: Soares Jair C. , Gershon Samuel
Published: August 2007

The authors reviewed historical data in the development of THA, as well as recent data on its pharmacological properties and therapeutic effects on cognitive dysfunction. A medline search was conducted to identify the trials conducted with THA in Alzheimer''s disease (AD) patients. The findings seem to lend support to some palliative action of THA, especially at higher doses, but in these doses about 2/3 of the patients experience significant adverse reactions. The significance of these findings is discussed, with emphasis on the their relevance for the management of AD patients.
Tetraethylammonium-Induced Calcium Concentration Changes in Skin Fibroblasts from Patients with Alzheimer Disease
Authors: Matsuyama Steven S. , Yamaguchi Dean T. , Vergara Julio , Jarvik Lissy F.
Published: August 2007

Potassium (K+) channel dysfunction in fibroblasts was recently proposed as a potential diagnostic marker for Alzheimer disease (AD). We utilized a micro-spectrofluorometric method with Fura-2AM to measure intracellular free calcium ([Ca2+]i) following depolarization with the K+ channel blocker tetraethyl-ammonium (TEA) in seven AD and seven control fibroblast cultures. Contrary to our expectation, 43% of the AD and 36% of the control fibroblast plated coverglasses responded with an increase in [Ca2+]i on addition of 100 mM TEA. The data suggest that the TEA-elicited [Ca2+]i response is not a useful AD screening test.
Long-Term Effects of Tacrine on Regional Cerebral Blood Flow Changes in Alzheimer’s Disease
Authors: Minthon L. , Nilsson N. , Edvinsson L. , Wendt P.E. , Gustafson L.
Published: August 2007

Regional cerebral blood flow (rCBF) was studied in patients with Alzheimer''s disease (AD) before and after 14 months of tacrine treatment. The treated group was compared with an identical reference group of untreated AD patients. At baseline the two groups showed an identical rCBF and mean hemispheric blood flow. After 14 months the tacrine-treated patients showed a stable rCBF level and a signiflcant increase in rCBF in the central-parietal regions, compared to the untreated reference group, who showed typical AD reductions in rCBF in these regions. Clinical outcome: 7 of 9 patients in the tacrine group were clinically unchanged or slightly improved during the study time. In the untreated group 8 of 11 patients had deteriorated in clinical assessments and none had improved. Long-term tacrine treatment in Alzheimer''s disease may delay the progression of symptoms.
EEG Findings in Dementia Are Related to the Parietal Lobe Syndrome
Authors: Edman Åke , Matousek Milos , Wallin Anders
Published: August 2007

EEG indicators were correlated with clinical items in 174 patients with dementia diagnoses based on the DSM-III-R criteria. The patients'' clinical symptomatologies were presented as regional brain syndromes, i.e. parietal lobe, frontal lobe, subcortical and global (nonregional) syndromes. The EEGs were abnormal in 87% of the cases. The typical abnormalities consisted of diffusely distributed slow wave activity. A significant correlation was found between the degree of slow wave abnormality and the degree of dementia. The results of the statistical analysis also suggest that EEG slow wave activity in dementia primarily reflects parietal lobe dysfunction. No association seems to exist between EEG slow wave activity and frontal lobe dysfunction.
Prevalence and Drug Treatment of the Parkinsonian Syndrome in Malta
Authors: Serracino Inglott Anthony , Farrugia Simone , Ferrito Mary Nancy
Published: August 2007

The prevalence of the parkinsonian syndrome in Malta was determined from a retrospective study conducted on 34 patients who were suffering from the parkinsonian syndrome at a geriatric residence. A crude prevalence rate of 92.8 per 100,000 population was obtained. Idiopathic Parkinson''s disease was the most common variant. A study of drug treatment showed that a longer improvement period is obtained by initiating de novo parkinsonian patients on anticholinergic drug treatment and then transferring them to L-dopa-carbi-dopa when disease progression renders anticholinergic drug treatment inefficacious.
Regional Distribution of Paired Helical Filaments and Normal Tau Proteins in Aging and in Alzheimer's Disease with and without Occipital Lobe Involvement
Authors: Mukaetova-Ladinska E.B. , Harrington C.R. , Hills R. , O’Sullivan A. , Roth M. , Wischik C.M.
Published: August 2007

A characteristic hallmark of Alzheimer''s disease is the presence of neurofibrillary tangles which consist of paired helical filaments (PHFs) in the brain. Tau protein, which is normally an axonal microtubule-associated protein, becomes incorporated into PHFs that accumulate in the somatodendritic compartment of neurons in Alzheimer''s disease. We have examined the regional distribution of PHF-bound tau and normal tau proteins in aging and in Alzheimer''s disease using immunoassays which selectively measure these two immunochemically distinct presentations of tau protein in brain tissue. Normal, soluble tau protein levels were decreased in Alzheimer''s disease, the most affected regions being frontal and temporal cortices. Accumulation of tau protein in PHFs, that was restricted largely to the grey matter, was greatest in entorhinal and temporal cortices. The PHF-bound tau content, measured biochemically, matched the neurofibrillary pathology observed immunohistochemically. In 2 out of 14 Alzheimer''s disease cases, very high PHF levels were observed in the occipital lobe. This correlated with an abundance of tau-immunoreactive dystrophic neurites throughout the neuropil and around neuritic plaques in the absence of significant numbers of neurofibrillary tangles.
Changing Patterns of Hospital Survival in Dementia
Authors: Ryan D.H.
Published: August 2007

The hospital survival time (first admission to death) of married male and female dementia patients was contrasted for two periods (1971–1975 and 1976–1986). Between the two periods the median survival time fell from 0.9 years to 0.5 years for male patients, and from 2.2 years to 1.6 years for female patients. Over the same intervals there was a significant increase in the mean age of female patients from 75.7 to 77.3 years (p < 0.025), and in the mean age of male patients from 76.2 to 77.4 years (p < 0.01). Hospital survival time fell as patient age on first admission increased, and there was a highly significant correlation between patient age on admission and hospital survival time for male patients (p < 0.01), and for female patients (p < 0.01). There was no evidence of a significant relationship between hospital survival time and year of admission for the period 1971–1986 after controlling for age, and age-related hospital survival was stable over the period of the study. The relationship between patient age on admission, and age at death was studied for the period 1971–1986 by means of linear regression statistics. The linear regression accounted for 89% of the variance for female patients, and 93% of the variance for male patients. Hospital survival of dementia patients could therefore have been predicted with a high degree of accuracy within the service described. No evidence was found of the prolonged hospital survival of female patients aged 85 years and over noted by other workers. Extreme old age was associated with shortened hospital survival and calculations of future bed requirements based on beliefs about the prolonged hospital survival of patients in their ninth decade should be re-examined.
Neuropathology of Late Life
Authors: Brun Arne , Gustafson Lars , Samuelsson Sven Mårten , Ericsson Catarina
Published: August 2007

In the oldest age group of dementia, patients dying after age 80, 38 cases were studied clinically and neuropathologically. In comparison with dementia cases dying at younger ages the disease panorama dififered in important respects. In the older age group frontal lobe dementia of non-Alzheimer type was entirely absent but trauma was much more common as were also cerebrovascular diseases. Dementia of the Alzheimer type was in many cases milder than in younger age groups and a mild, subclinical Alzheimer encephalopathy often complicated the cerebrovascular disorders. In this context, it may be of interest that some of the patients died from diseases not directly connected with the dementing disorder such as heart failure, Cancer and pulmonary embolism, suggesting that the dementing disorders did not necessarily repre-sent an end stage. Contrary to our previous opinion Alzheimer disease in these aged patients was of a very long duration, in many cases lasting 7-13 years. Labile blood pressure and orthostatism presented further prominent Problems. The mild Alzheimer changes, in 1 case precluding a distinct diagnosis, may be taken as a harbinger of the vague changes found in 3 centenanans, 2 of whom had dementia. They suffered from changes of an Alzheimer encephalopathy of a subclinical severity, mild frontal white matter degeneration and a loss of frontal cortical neurons, changes that would be difficult to diagnose in life and which may be the cause of the real dementia of the senium.
Diagnosis of Dementia in Patients in Long-Term Somatic Care
Authors: Bråne Görel , Karlsson Ingvar , Kihlgren Mona , Norberg Astrid
Published: August 2007

A study was undertaken to investigate the frequency and accuracy of dementia diagnosis in two Swedish nursing homes. The diagnoses of 46 patients were registered from the medical records on the wards. Then the patients were reinvestigated and diagnosed according to DSM-III-R. Ratings were performed using two instruments, the Gottfries-Bråne-Steen scale (GBS scale) and the Mini-Mental State Examination (MMSE). The results of the psychiatric reinvestigation and the ratings showed that 45 of the 46 patients had dementia, while, according to the ward records, dementia was diagnosed in only 9 cases. The discrepancy was striking. The unawareness of dementia in the nursing homes was thus considerable and may have had implications for the planning and quality of the care. Education of the staff with regard to dementia must also be considered. The use of a rating scale for identification of dementia symptoms is suggested.
Central Benzodiazepine-Binding Sites in Human Cerebral Structures Associated with Memory Processes
Authors: Eymin C. , Kopp N. , Laurent B. , Martin D. , Simon L. , Miachon S.
Published: August 2007

This work describes the distribution of the central benzodiazepine-binding sites (BZD-BS) in several structures recently described as involved in memory processes. The study was performed on 4 postmortem human brains by in vitro quantitative autoradiography using 3H-flunitrazepam as a ligand. Very high densities of BZD-BS (1,500–2,000 fmol/mg protein) were observed in the anterior and posterior cingulate cortex, in the indusium griseum and in the accessory basal nucleus of the amygdala, and moderate concentrations (500–700 fmol/mg) in the magnocellular region of the mediodorsal thalamic nucleus. In the classical cerebral memory circuits, high densities of BZD-BS (1,000 to 1,500) were also found, except in the septum where the density of BZD-BS (400 to 600) was not significantly different from that in control structures not involved in memory. No evidence for lateralization of the sites was observed.
Receptor Changes in the Neocortex of Post-Mortem Tissue in Parkinson's Disease and Alzheimer's Disease
Authors: Griffiths P.D. , Crossman A.R.
Published: August 2007

Benzodiazepine and muscarinic receptors in the neocortex were studied using homogenate binding techniques and in vitro autoradiography (ARG). Tritiated flunitrazepam was used to bind to the benzodiazepine portion of the γ-aminobutyric acid receptor. Tritiated quinuclidnyl benzilate was used to locate the muscarinic receptor. Tissue samples from four areas of neocortex from cases of Parkinson''s disease, Alzheimer''s disease and age-matched controls were used for homogenate binding experiments to estimate binding parameters. Tissue for ARG provided more detailed anatomical localization of the relevant receptors. Homogenate binding studies showed that the receptor density, as measured by maximum binding capacity for tritiated flunitrazepam, was significantly reduced in the frontal cortex in Parkinson''s disease. In Alzheimer''s disease there was reduced binding of flunitrazepam in all portions of the neocortex studied, reaching statistical significance in the frontal and temporal cortex. The dissociation constant, indicating receptor affinity for flunitrazepam, was unaltered in all areas studied. ARG demonstrated that the distribution of benzodiazepine receptor loss within different cortical layers was distinct in Parkinson''s and Alzheimer''s disease. In control brains, the greatest density of benzodiazepine receptors was seen in regions corresponding to layers II and III. This peak was greatly reduced in the frontal cortex of Parkinson''s disease, while in Alzheimer''s disease the loss was more uniform. There was no significant alteration in the binding parameters of the muscarinic cholinergic receptors in either of these disease states.