Alzheimer's disease

The changes which Alzheimer associated with this disease are still a major focus of interest in pathological studies, but their relative importance and association to symptoms is still not clear. The diagnosis of early Alzheimer's disease (AD) is a very difficult clinical problem since there is no pathognomic test. It can be particularly difficult to differentiate the condition from depressive illness. Despite doubts about the significance and specificity of the cholinergic deficit in AD, attempts at therapy with cholinergic drugs have been made. Physostigmine has produced some small improvements, but it is not yet known whether the drug is clinically useful or not. Its utility may be limited by its short half-life. Other approaches to management of AD should not be neglected. Increased publicity concerning AD is a potential source of stress to the elderly generally, but increased awareness of this disease both by the general public and health professionals has probably helped support and management of AD.     

Visual spatial perception and surgical competence

BACKGROUND: Proficiency in visual spatial perception (VSP) is a hypothetical component of surgical competence. METHODS: Four tests of VSP, taken from the Cognitive Laterality Battery (CLB), were administered to 301 surgeons and surgical residents. Mean scores on each test were compared by Student t tests to those of the normative sample (n = 251) on which the test was originally standardized. RESULTS: Mean scores on two of the tests (Orientation, Touching Blocks) were significantly greater (P <0.01) for the study sample than for the normative sample, while mean scores on the other two subtests (Form Completion, Localization) were not. CONCLUSIONS: Surgeons tend to outperform the general population on tests of high-level VSP abilities (ie, envisioning depth and mentally manipulating two-dimensional representations of three-dimensional structures) identified previously as correlates of surgical skill acquisition. VSP proficiency is a valid component of surgical competence that should perhaps be included in career selection discussions with medical students and in assessment of the competence of surgeons.     

Multiconceptual therapy in Alzheimer's disease

SOCIAL AND ECONOMICAL IMPACT: Alzheimer's disease is a neurodegenerative dementia raising major public health concern in industrialized countries. The consequences are not only medical but also social and economical. PERSPECTIVES: It is thus important to establish diagnostic principles, therapeutic goals, and global strategies guiding the behavior of physicians, family and patients faced with this dreaded disease. Currently, only a few rare symptomatic treatments are available, but research in this field points to potentially effective preventive and etiopathogentic therapeutic protocols associating drugs, social support, and psychotherapy.     

Hypertension and Alzheimer's disease

Case-control transversal studies have suggested the existence of an association between low blood pressure and Alzheimer's disease, although there is some doubt on the cause to effect relationship. A drop in blood pressure preceding the onset of dementia has been evoked but never confirmed. Longitudinal studies, with long term follow-up on the existence of hypertension during middle-age, have demonstrated a significant increase in the risk of developing Alzheimer's disease in cohorts of hypertensive patients compared to normotensive subjects. The potential benefit of preventive treatment with antihypertensive drugs in decreasing the risk of Alzheimer's disease has not been confirmed in clinical trials. The hypothesis of the formation of a cerebrovascular disease that would combine with the neuropathological lesions has been evoked, raising doubts on the diagnostic criteria used to define Alzheimer's disease. The novel concept that vascular risk factors could directly induce the formation of neuropathological lesions is interesting but warrants confirmation.     

Alzheimer's disease and anaesthesia

Editor—It was with particular interest that we read thereview article by Fodale and colleagues¹ on Alzheimer's disease(AD) and anaesthesia. In the same month, our department receiveda letter from the family of an 80-yr-old lady diagnosed 4 yrpreviously with AD. She had undergone an elective hip replacementin 1998. The patient received a general anaesthetic using isofluraneand the operation, lasting 2 h, was unremarkable. At aroundthis time, the family report that the patient started experiencingincreasing problems with her memory. Having read a recent article²in the New Scientist titled ‘Alzheimer's alert over anaesthetics’,in which Mandal is quoted as saying ‘It's a seriouslydeadly     

Alzheimer's disease with refluxes

This is a report concerning a unique combination of Alzheimer's disease with the following refluxes: buccosalivary, gastroesophageal, vesicoureteral, urethroprostatic and urethrovesicular, along with neurogenic bowel and neuropathic bladder. A second patient with Alzheimer's disease and vesicoureteral reflux is reported. The possible etiopathology of these unusual refluxes and their relation to Alzheimer's disease are discussed.     

Orbitofrontal cortex pathology in Alzheimer's disease

The orbitofrontal cortex has been examined in Alzheimer's disease (AD) from the viewpoint of neurofibrillary tangle (NFT) pathology, its laminar distribution and topography. NFT pathology in the orbitofrontal cortex is extensive in AD. In cases with extensive cortical pathology, NFTs extend from the pole of the frontal lobe to the orbitoinsular junction. In lesser affected cases, the anterior granular part of the orbital cortex is less invested by NFTs. Layers III and V contain the greatest density of NFTs and these are most dense in the dysgranular areas, posterior to the transverse orbital sulcus. Posterior and medial orbitofrontal areas, forming area 13 and the posterior tip of the paraolfactory gyrus, are the most severely damaged, as are the smaller agranular fields that surround the olfactory tract and cortex. The widespread orbitofrontal damage in AD affecting projection neurons suggests that this pathology may contribute heavily to the many non-memory-related behavior changes observed in this disorder.     

The neurobiology of Alzheimer's disease

The defining histological characteristics of Alzheimer's disease (AD) are neurofibrillary tangles and neuritic plaques, although neither is pathognomonic for this disorder. The distribution of AD histopathology suggests selective neuronal vulnerability, with specific cell populations affected within discrete regions of the cerebral hemispheres and within certain subcortical and brain-stem nuclear areas. At the ultrastructural level, tangles and plaque neurites contain paired helical filaments whose composition is unknown but may include altered cytoskeletal elements. Amyloid, deposited in plaque cores and often focally present within the cerebral vasculature, contains a polypeptide ("beta-protein," or "beta-amyloid") encoded by a chromosome 21 gene. At least in occasional families, AD has been linked to a separate chromosome 21 locus, but different underlying genetic factors may operate in other cases. Inorganic substances, including aluminum and silicon, are reported to co-localize within tangle-bearing neurons and plaque cores. Specific environmental agents have not been confirmed to be pathogenetically important, however, but may eventually prove to exert a permissive, facilitatory, or even causative role in many AD patients.     

Familial forms of Alzheimer's disease

TWO SITUATIONS: Familial occurrence of Alzheimer disease is observed in two quite different situations. The more common is the familial aggregation caused by the Apo E4 genotype. Nevertheless, APO E4 as a major risk factor is neither sufficient nor necessary to induce Alzheimer disease. The second possibility are the autosomal dominant forms of Alzheimer disease. Three different genes are concerned. MUTATIONS: The more frequent mutations are found in the Presenilin 1 gene (PS1), mutations in the amyloid precursor protein (APP) are rare and only a few Presenilin 2 gene (PS2) mutations are reported. CHARACTERISTICS: The main clinical characteristic of these autosomal dominant forms is an early age of onset below 60. Neuropathology is similar to sporadic cases: senile plaques with A beta peptide as a major component and neurofibrillary tangles containing Tau protein. MECHANISMS: The demonstration that both APP, PS1, and PS2 gene mutations enhance the processing of APP to form A beta peptide is a major argument supporting the amyloid hypothesis of Alzheimer disease. This better knowledge of APP and PS1,2 processing and their interactions with binding proteins does permit to develop treatment strategies.     

Immunopathogenetic mechanisms in renal disease

This review deals with various immunopathogenetic mechanisms of renal diseases. Although immune-complex nephritis was long thought to be the result of deposition of circulating immune complexes, recent studies have revealed the importance of in situ formation. In experimental Heymann nephritis, an antigen (gp 330) has been localized on glomerular epithelial cells, and antibodies reactive with gp 330 have been eluted from glomeruli; deposits appear to result from shedding of complexes from the podocyte surface into the basement membrane. In human disease, it seems likely that mesangial and subendothelial deposits most often result from deposition of circulating immune complexes, whereas subepithelial deposits are formed mainly in situ. Cell-mediated immune mechanisms are capable of producing glomerular injury, as shown in experimental models. In humans, Wegener's granulomatosis and idiopathic crescentic glomerulonephritis may involve such mechanisms. In certain forms of experimental and human tubulointerstitial nephritis, cell-mediated immunity also seems to play an important role.     

Anesthetic considerations in patients with Alzheimer's disease

Alzheimer's disease is a form of dementia that is estimated to affect approximately 3 to 4 million Americans. Given the substantial number of people affected with this disease, it is likely that anesthesiologists will encounter many patients with Alzheimer's disease. Questions as to potential problems including informed consent, drug interactions, and preoperative progression of the disease may arise. This review describes anesthetic considerations, including pharmacologic and physiologic issues, in this growing population.     

Vascular mechanisms in Meniere's disease

Normal venous drainage of the vestibular organs through the vein of the paravestibular canaliculus (PVC) may be crucial to inner ear fluid mechanics. It is proposed that increased venous pressure, with resultant venous insufficiency of the vestibular organs, may result in endolymphatic hydrops unless collateral venous circulation develops. Certain variations in pattern of venous drainage where the vestibular organs drain predominantly through the PVC vein may be a predisposing factor. In patients with Meniere's disease, different mechanisms can cause venous insufficiency. One suggested mechanism is morphologic change in the microcirculation of the intermediate portion of the endolymphatic sac. Microcirculation changes may be associated with fibrosis of the perisac tissues or shortening of the intermediate sac region or might be physiologically determined. Venous insufficiency may also result from anomalies of the PVC vein.     

The autonomic-related cortex: pathology in Alzheimer's disease

Alzheimer's disease (AD) causes progressive deterioration of cognition and behavior. Memory dysfunction is the hallmark, but there are also changes in behavior, emotion and autonomic functions, which cannot be explained simply as a consequence of memory impairment. These observations suggest that the natural disease process of AD involves not only memory-related neural structures, but also specific neural systems related to other behaviors, emotion and autonomic functions. Since recent evidence has indicated a primary role for ventromedial frontal (VMF) cortex in such functions, we examined laminar distribution of neurofibrillary tangles and Alz 50 immunoreactive neurons in subdivisions of VMF cortex in 20 AD patients and seven age- matched controls. The densities of pathological changes were: (i) highest in the posteromedial mesocortical regions, particularly Brodmann's area 25 (A25), posterior orbitofrontal cortex (POF) and anterior insula (AI); (ii) of comparable severity between posteromedial mesocortical regions and most temporal cortices, excluding only the entorhinal cortex and temporal pole; and (iii) located predominantly in layer III and especially layer V. Further analysis demonstrated selective pathology in layer V of A25, POF and AI that would disrupt direct cortico-autonomic projections. This is the first study to detail severe AD pathology in these autonomic-related cortices, which could contribute to the behavioral changes, emotional disturbance and autonomic dysregulation that often accompany AD.      

Diagnosis of psychological and behavioural disorders in Alzheimer's disease

Although Alzheimer's disease has long been considered mainly a cognitive disorder, behavioral and psychological symptoms are present from its onset and at all the stages of the disease in most patients. They must be identified from the beginning because they orient the diagnosis. They include affective and emotional disorders, delusions and hallucinations, disorders of instinctual behavior and behavioral problems. The best tool for assessing them is the Neuropsychiatric Inventory (NPI). They are generally related to neurobiological aspects of the disease but may, especially when acute, have multiple etiologies: somatic, iatrogenic, psychological and environmental. They condition the course of the disease. As a source of suffering and reduced quality of the life and as the primary cause of distress for the caregivers and hence of hospitalization and institutionalization, they increase the costs of care. The challenge today is to learn more about them and thus improve their treatment and especially their prevention.     

Small-world networks and functional connectivity in Alzheimer's disease

We investigated whether functional brain networks are abnormally organized in Alzheimer's disease (AD). To this end, graph theoretical analysis was applied to matrices of functional connectivity of beta band-filtered electroencephalography (EEG) channels, in 15 Alzheimer patients and 13 control subjects. Correlations between all pairwise combinations of EEG channels were determined with the synchronization likelihood. The resulting synchronization matrices were converted to graphs by applying a threshold, and cluster coefficients and path lengths were computed as a function of threshold or as a function of degree K. For a wide range of thresholds, the characteristic path length L was significantly longer in the Alzheimer patients, whereas the cluster coefficient C showed no significant changes. This pattern was still present when L and C were computed as a function of K. A longer path length with a relatively preserved cluster coefficient suggests a loss of complexity and a less optimal organization. The present study provides further support for the presence of "small-world" features in functional brain networks and demonstrates that AD is characterized by a loss of small-world network characteristics. Graph theoretical analysis may be a useful approach to study the complexity of patterns of interrelations between EEG channels.     

Interaction of donepezil and muscular blockers in Alzheimer's disease

A 75-years-old man with Alzheimer's disease, treated with the cholinesterase inhibitor donepezil for 14 months, was scheduled for left colectomy under general anesthesia. During the procedure, succinylcholine-induced relaxation was prolonged and the effect of atracurium besylate was inadequate even at higher doses than those indicated for the patient's weight. Cholinesterase blood tests performed 10 months, 1 month and 10 days before surgery had demonstrated a gradual decrease in the duration of activity of the enzyme. Such an effect, which has been described for cholinesterase inhibitors like neostigmine and donepezil, would explain the prolonged effect of succinylcholine. After ruling out other causes for resistance to atracurium, we conclude that donepezil or its metabolites acted on muscle plaque, blocking acetylcholine hydrolysis and antagonizing atracurium.