Repeated prenatal corticosteroids delay myelination in the ovine central nervous system

In the near future the number of patients suffering from cognitive impairment and senile dementia will increase because of the change in the structure of population. General practitioners and specialists will be confronted with this problem. The early and differential diagnosis of senile dementia is still a problem. Corresponding with the diagnostic algorithms of ICD 10 and DSM IV the diagnostic procedure is discussed with geriatric, neuro/psychiatric, psychological and psychosocial aspects. The diagnosis also relies on history obtained from family and friends. Although cognitive loss is considered a core symptom of senile dementia, loss of behavioral disinhibition, loss of functional autonomy and mood problems are considered as more important by clinicians and family and are of great diagnostic value. Psychometric tests are important but they are only one out of many different possibilities to find the right diagnosis. If it is possible different specialists should examine the patient. Out of the different methods and views of the specialists a comprehensive image of the patient takes shape and allows a better understanding of dementia.     

British Thoracic Society guidelines for the management of spontaneous pneumothorax: do we comply with them and do they work?

Propentofylline (Karsivan, Hoechst Roussel Vet) is a selective inhibitor of adenosine transport and phosphodiesterase. For several years it has been well established in the geriatric therapy of the dog improving hemodynamics in cerebral and peripheral compartments. In human medicine clinical development of this pharmaceutical has already entered an advanced stage for the long-term therapy of patients with Alzheimer's disease and vascular dementia. In the brains of senile dogs and in human patients suffering from Alzheimer's disease comparable neuropathological findings can be made. In senile dogs a distinctive correlation exists between the quantity of beta-amyloid accumulation and the degree of dementia. The extension of knowledge by clinical studies in humans and by experimental studies in animals may contribute to a deeper understanding of therapeutical approaches of cognitive dysfunction in the old dog. The xanthine derivative propentofylline [1-(5'-oxohexyl)-3-methyl-7-propylxanthine] directly interfers with the neurodegenerative process and reduces the extent of damage to brain structures. In experimental models of vascular dementia and/or Alzheimer's disease it improves cognitive functions, inhibits inflammatory processes as well as excessive activation of microglia, formation of free radicals, cytocines and abnormal amyloid precursor proteins (APP). It stimulates synthesis and liberation of nerve growth factor (NGF) and reduces ischemic damage to the brain. In clinical studies in humans it improved cognitive functions as well as global functions and the ability to cope with tasks of routine daily life in patients suffering from Alzheimer's disease and vascular dementia.     

Quantitative analysis of neuropathologic changes in the cerebral cortex of centenarians

1. The quantitative distribution of neurofibrillary tangles and senile plaques was studied in the brains of 65 elderly patients aged from 96 to 104 years by immunohistochemistry. 2. According to the clinical and neuropathological diagnoses, three groups of cases were considered: 19 patients with Alzheimer's disease, 22 patients with mixed dementia (vascular and degenerative) and 24 patients with no or very mild cognitive impairment. 3. Moderate to high neurofibrillary tangle densities were always present in the hippocampus and entorhinal cortex. The inferior temporal cortex was very frequently affected in demented and non-demented cases whereas the superior frontal cortex was spared in the majority of cases independently of the clinical diagnosis. Quantitatively, Alzheimer's disease cases showed significantly higher NFT densities than cases with no clinical findings of dementia only in the CA1 field of the hippocampus. 4. The hippocampus and entorhinal cortex were often devoid of senile plaques in non-demented cases while the vast majority of Alzheimer's disease cases had few SP in these regions. The frontal and temporal cortex were more frequently involved than the limbic structures in both non-demented and Alzheimer's disease cases. The SP densities in layers II and III of the inferior temporal and superior frontal cortex were significantly higher in Alzheimer's disease than in non-demented cases. 5. These observations suggest that the dementing process in nonagenarians and centenarians may differ to that described in younger demented individuals in that neurofibrillary tangles involve principally the hippocampal formation with relative sparing of the neocortex. Furthermore, they indicate that both the neurofibrillary tangle densities in the CA1 field and senile plaque densities in the superficial layers of the neocortex must be considered for the neuropathological diagnosis of Alzheimer's disease in this age group.     

Is it Alzheimer's?

The diagnosis of Alzheimer's disease includes documentation of cognitive impairment and exclusion of other causes of dementia. Screening of mental status can be performed by the primary care physician or by a neuropsychologist for a more in-depth assessment. Testing for genetic markers has a clearly defined role only in patients with a family history of early-onset disease.     

Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study

BACKGROUND: Previous studies suggested a protective effect of smoking on Alzheimer's disease, but most were case-control studies based on prevalent cases. The findings of prospective studies on the association between smoking and the risk of dementia are inconclusive. METHODS: We did a population-based follow-up study of elderly people who were initially free of dementia. 6870 people aged 55 years and older agreed to take part. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers. During follow-up, we recorded all incident cases of dementia. We used never smokers as the reference category to calculate relative risks of dementia and Alzheimer's disease by Cox proportional hazards regression, after adjustment for age, sex, education, and alcohol intake. We also examined modification of risk by age, sex, and the apolipoprotein E (APOE) genotype. FINDINGS: During mean follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were detected, of which 105 were Alzheimer's disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for Alzheimer's disease in individuals without the APOEepsilon4 allele (4.6 [1.5-14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]). INTERPRETATION: Smoking was associated with a doubling of the risk of dementia and Alzheimer's disease. Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimer's disease.     

Fat-soluble vitamin therapy in senile dementia and Parkinson's disease

In the pathogenesis of Parkinson's disease and senile dementia of the Alzheimer type, free radicals might play a role. Fat-soluble vitamins are a kind of anti-oxidative substance. Therefore, fat-soluble vitamins, such as vitamin E, may be useful in treatment of Parkinson's disease and senile dementia of the Alzheimer type. However, it is still unclear whether the concentration of vitamin E in the blood or in the brain tissue, in patients with Parkinson's disease or with of the senile dementia Alzheimer type, is higher than or the same as that in normal subjects. Furthermore, although the effectiveness of vitamin E in the treatment of Parkinson's disease has been reported, the usefulness of vitamin E is still obscure. Further study will be necessary, in order to clarify the role of fat-soluble vitamins in the treatment of Parkinson's disease and senile dementia of the Alzheimer type.     

Resident resistance

Despite their severe and global cognitive impairments, some patients with Alzheimer's disease or vascular dementia continue to perform some complex mental activities skillfully. This paper briefly describes the artistic and game-playing skills of dementia patients, presents preliminary findings indicating that dementia patients with preserved skills exhibit slower cognitive deterioration than patients without retained cognitive skills, and illustrates how caregivers and other persons can utilize preserved abilities in the management of agitated and disruptive behavior.     

Presenilin 1 intronic polymorphism is not associated with Alzheimer type neuropathological changes or sporadic Alzheimer's disease

BACKGROUND: A genetic association between the presenilin 1 (PS-1) intronic polymorphism and sporadic Alzheimer's disease has been a matter of controversy. Recent findings have suggested that the PS-1 polymorphism is not associated with Alzheimer's disease or amyloid beta-protein (Abeta) deposition in brains from patients with Alzheimer's disease. OBJECTIVES: To elucidate the influence of the PS-1 polymorphism on Alzheimer type neuropathological changes and the development of Alzheimer's disease, the relation between the PS-1 polymorphism and quantitative severity of Alzheimer type neuropathological changes in the brains from patients with Alzheimer's disease and non-demented subjects was studied. METHODS: The PS-1 and apolipoprotein E (ApoE) genotypes, were examined, together with the densities of the senile plaques, senile plaques with dystrophic neurites, and neurofibrillary tangles in the brains from 36 postmortem confirmed patients with sporadic Alzheimer's disease and 86 non-demented subjects. Association of the PS-1 polymorphism with sporadic Alzheimer's disease and ages at onset and duration of illness in Alzheimer's disease was also examined. RESULTS: The PS-1 polymorphism was not associated with the senile plaques, senile plaques with dystrophic neurites, or neurofibrillary tangles in Alzheimer's disease or non-demented subjects. There was no association of the PS-1 intronic polymorphism with Alzheimer's disease, ages at onset, or durations of illness in Alzheimer's disease. The results remained nonsignificant even when the PS-1 genotype groups were divided into the subgroups with different ApoE epsilon4 status. CONCLUSIONS: The PS-1 intronic polymorphism does not itself have a direct causal role in the formation of Alzheimer type neuropathological changes or in the development of sporadic Alzheimer's disease.     

The case described by Alois Alzheimer in 1911. Historical and conceptual perspectives based on the clinical record and neurohistological sections

In 1906, Alzheimer presented the first case of the disease which was later named Alzheimer's disease by Kraeplin. While the publication on this case in 1907 is only a relatively short communication, Alzheimer published a very comprehensive paper in 1911 in which he discussed the concept of the disease in detail. This publication focusses on the report of a second patient suffering from Alzheimer's disease, the case of Johann F. The detection of neurohistopathological sections from this patient found among archives at the Institute of Neuropathology of the University of Munich enabled us to reinvestigate this case using modern methods. Neurohistopathologically, the case of Johann F. is "plaque-only" Alzheimer's disease. There is a controversy in the modern literature as to whether these "plaque-only" cases belong to the modern concept of Alzheimer's disease. A careful analysis of all pros and contras in the literature led to the conclusion that plaque-only cases are also an integrative part of the modern Alzheimer disease concept.     

Conceptual foundations of IQ testing.

Cognitive neuroscience has not yet arrived at a definition of what human "intelligence" is. Intelligence is a chapter-heading word used in the 19th century to denote some unspecified mental property that increases in evolution. Other words were given speculative evolutionary meanings in the 19th century: genius, degeneracy, retardation. When the Binet-Simon test came along as a test to screen degrees of mental retardation, later as a pupil classification instrument, some (not Binet) associated the test with these 19th-century words and meanings. Descendants of the Binet-Simon instrument, IQ tests, remain useful today, but the old legendry lives on with them, at times supporting speculative social and political arguments. Researchers need to disentangle what is factual about IQ testing from its associated legendry. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alzheimer's disease and its Lewy body variant: a clinical analysis of postmortem verified cases

OBJECTIVE: The authors compared clinical findings of Alzheimer's disease and the so-called Lewy body variant of Alzheimer's disease. METHOD: Available data were analyzed on the clinical features of 58 patients with Alzheimer's disease and 24 patients with the Lewy body variant of Alzheimer's disease who underwent postmortem examination. RESULTS: The proportion of men was significantly larger in the Lewy body variant group than in the Alzheimer's disease group (66.7% versus 34.5%), and, concordantly, the Lewy body variant group was slightly taller. The prevalence of hallucinations and delusions was significantly higher in Lewy body variant subjects than the Alzheimer's disease subjects, but there were no significant differences between the two groups in educational attainment, family history of dementia, age at onset, duration of illness, cognitive impairment, overall severity of illness, or neuropsychological findings. Patients with the Lewy body variant of Alzheimer's disease tended to experience more frequent extrapyramidal side effects of neuroleptics than did the patients with Alzheimer's disease, but for patients in the two groups who were not exposed to neuroleptics, there was little difference in frequency of extrapyramidal side effects. CSF concentration of homovanillic acid (HVA) was significantly lower in the Lewy body variant patients, even when correction was made for height. CONCLUSIONS: The Lewy body variant of Alzheimer's disease may be suspected in elderly male dementia patients who otherwise meet criteria for Alzheimer's disease but who manifest significant psychiatric symptoms and neuroleptic-induced extrapy-ramidal side effects and have low levels of CSF HVA.     

Elderly patients with schizophrenia exhibit infrequent neurodegenerative lesions

Immunohistochemistry and conventional stains were used to examine the brains of 10 elderly patients with both schizophrenia and dementia to characterize the neuropathology of their cognitive deterioration. Control cases included five nondemented elderly patients with schizophrenia, five age-compatible Alzheimer's disease (AD) patients, and five neurologically normal elderly patients. Only one of the patients with schizophrenia and dementia had AD, another was diagnosed with adult polyglucosan body disease, and the others were devoid of neuropathology that could account for dementia. Quantitation of immunohistochemically detected neurofibrillary tangles and senile plaques revealed similarly low counts for the normal control group and both schizophrenia groups. Typically, the neuropathological causes of dementia can be identified in up to 95% of cases, with AD accounting for 50-60%. The unexpected lack of neuropathological findings to explain the cognitive deterioration in this group of elderly patients with schizophrenia prompts speculation about alternative etiologies.     

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain.     

Neuropsychologic method in diagnosis of mild dementia in elderly and senile patients

Clinical neuropsychologic investigation was performed in 95 patients of elderly and senile age with mild dementia: 20 individuals with Alzheimer's disease (AD), 25 patients with senile dementia of Alzheimer's type (SDAT), 25 patients with vascular dementia (VD) and 25 patients with combined dementia of vascular and Alzheimer's types (DAT/VD). Clinical diagnosis of mild dementia was performed according to ICD-10. Neuropsychologic study was based on the theory and method of A.R. Luria. Syndrome of disorder of high psychic functions (HPF) in patients with mild SDAT was characterised by pathology of frontal cerebral structures and by significantly less defects of profound cerebral structures. According to the examination results the group of patients with mild AD was divided into 2 subgroups: 1) patients in which syndrome of HPF disorders was determined by pathology of parietal-temporal and profound cerebral structures and 2) patients with dysfunction of profound and frontal cerebral structures. Symptoms associated with profound cerebral structures were the main ones in patients with mild VD. Syndrome of HPF disorder included in mild DAT/VD symptoms connected with subcortical and profound brain structures as well as with frontal structures too. Besides, there were also defects in posterior frontal and parietal structures of the brain.     

Anticipatory dementia: a link between memory appraisals and concerns about developing Alzheimer's disease

This exploratory study examines the link between memory appraisals and personal concerns about developing Alzheimer's disease. The sample of persons ages 40-60 includes adult children with a living parent who has Alzheimer's disease (N = 25) and a matched group with no family history of dementia (N = 25). Using two composite measures of memory appraisals, the results show significant bivariate and multivariate relationships between self-assessments of memory functioning and concerns about developing the disease. The findings also suggest that negative memory appraisals evoke concerns about developing Alzheimer's disease within both of the subsamples.     

Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of a Greek population

Many efforts have been made to trace the causes of Alzheimer's disease (AD). There are, however, many points of controversy among reports from the same country as well as among reports from different countries. The current study is a case-control study to determine the risk factors in the development of AD in Greece. Sixty-five patients with AD and 69 age-matched controls were examined. All patients with AD fulfilled the DSM-IV criteria for AD and NINCDS-ADRDA criteria for probable AD. Demographic characteristics such as gender, current marital status, who he/she is living with, education, main place of residence in childhood, adulthood, and late life, occupational hazards, patient's medical history (history of diabetes mellitus and hypertension), life habits like alcohol consumption and smoking, and a history of head trauma, heart attack, stroke, parkinsonism, or depression were collected from the subject or from an informant. A family history of selected diseases (hypertension, diabetes mellitus, dementia, Parkinson's disease, Down's syndrome, stroke) was also elicited. Ages of father and mother at birth were also recorded. Chi-square test, Kruskal-Wallis analysis of variance, cluster analysis, and logistic regression analysis were used for statistical analysis. The results (chi-square test) showed a statistically significant difference between patients with dementia of the Alzheimer type and controls as far as marital status (p = .04), the subject's history of major depressive episode (p = .02), and family history of dementia (p = .002) were concerned. Logistic regression analysis results produced a complex model of family aggregation of dementia, with patients with a history of depression and family history of dementia having an up to seven times higher risk of developing AD. These findings, especially a family history of dementia, are consistent with most of the literature.     

The role of cytokines during rejection of foetal pig and foetal mouse pancreas grafts in nonobese diabetic mice

Senile dementia of Alzheimer's type is frequently an underlying cause of accidental death of elderly persons. Neuropathological diagnosis of dementia is therefore crucial to assess the contribution of dementia to the cause of accident. The authors applied two conventional neuropathological criteria described by Khachaturian and Mirra, et al. to three forensic autopsy cases of dementia-related accidental death. In all cases, the number of neocortical senile plaque, a hallmark of dementia, could not fulfill both criteria. This result indicates that foregoing neuropathological criteria derived from fully developed dementia are hardly applicable to elderly persons who died in an early stage of dementia in forensic settings. Further investigation will be required to establish a diagnostic criterion of early stage of dementia.     

Postnatal depression: how can midwives help?

The results of recent neuropathologic and genetic studies in Alzheimer's disease led to a renewed interest in differentiations within the dementia syndrome. New disease-entities can be distinguished (Lewy Body Dementia, Frontal Lobe Dementia) and other criteria have been put forward for vascular dementia. Hachinski's Ischemic Score, for many years the diagnostic criterium for vascular dementia, has been cancelled. Instead a CT- or MRI scan must demonstrate the vascular pathology in the brain. For clinical practice, the differentiation between cortical and subcortical dementia is still important. For reasons of management it appears useful to distinguish between early-onset and late-onset Alzheimer's disease. The amyloid cascade hypothesis for the pathogenesis of Alzheimer's disease is credible for the early-onset as well as the late-onset type, because results from epidemiological as well as from neurobiological studies might be fit in. Moreover, this hypothesis is promising from the point of view of developing specific therapies. Finally, the breakdown of the dementia syndrome in separate disease-entities stimulated interest in the psychiatric symptoms in these patients and activated the development of rational and symptomatic therapeutics.     

Risk factors of dementia Alzheimer's type

The paper presents the study of risk factors and factors-protectors of the development of dementia of Alzheimer's type (DAT). 40 patients with Alzheimer's disease (AD), 40 patients, with senile DAT and 80 healthy individuals of the same sex, age and education level were examined. The pairs were formed: the patient-normal. The main risk factor in DAT group was family predisposition to dementia. AD risk factors may be the exposure to radioactive materials or chronic psychotraumatic situations during life. Senile DAT risk factors may be traumas of head without lack of consciousness. Acute and frequent psychotraumatic situations as well as some somatic diseases (and related drug therapy) were factors-protectors in the whole DAT group. Groups of patients with AD and senile DAT differed by both risk factors and factors-protectors, confirming DAT heterogeneity. Hypothetic biologic basis of the data obtained is described.     

Pharmacological and second messenger signalling selectivities of cloned P2Y receptors

An autopsy case of a 67-year-old man with typical clinical features of progressive supranuclear palsy (PSP) characterized by impairment of vertical ocular pursuit movement, pseudobulbar palsy, nuchal stiffness, parkinsonism, and dementia is described. In addition to typical pathological changes of PSP, the present case showed fronto-temporal cortical atrophy, accompanied with various Gallyas/tau-positive neuronal and glial structures such as neurofibrillary tangles, pretangle neurons, glial coiled bodies, astrocytic plaques and argyrophilic threads in the cerebral cortex and subcortical nuclei, and many senile plaques throughout the whole cerebral cortex. The present report suggests that PSP and corticobasal degeneration share a common background in neuronal and glial pathologies, that pathological changes of PSP and Alzheimer's disease are mixed in the entorhinal cortex, amygdala. Meynert nucleus, and hypothalamus, and that dementia with frontal lobe-like syndrome in PSP is related to the frontal and temporal cortical pathologies, and is cortical dementia as well as subcortical dementia.