Longitudinal diagnosis of memory disorders.

Early referral for specialist assessment is becoming more common with memory disorders and dementia: the mean Mini-Mental State Examination (MMSE) score of new patients at our clinic rose from 18.7 to 20.7 between 1986 and 1990.

Herpes simplex virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type.

We have investigated the possible involvement of viruses, specifically Herpes simplex virus type 1, in senile dementia of the Alzheimer type (SDAT). Using the highly sensitive polymerase chain reaction, we have detected the viral thymidine kinase gene in post-mortem brain from 14/21 cases of senile dementia of the Alzheimer type and 9/15 elderly normals. The temporal cortex and hippocampus were usually virus-positive; in contrast, the occipital cortex was virus-negative in 9/9 SDAT cases and 5/5 elderly normals.

Dementia and driving.

Many European countries test cars, but not their drivers, as they age. There is evidence to suggest that human factors are more important than vehicular factors as causes of motor crashes. The elderly also are involved in more accidents per distance travelled than middle-aged drivers.

Normal beta-NGF content in Alzheimer's disease cerebral cortex and hippocampus.

Nerve growth factor (beta-NGF) is known to have beneficial effects on cholinergic cell survival and to function both in vivo and in vitro. It has been speculated that this protein, or the lack of it, may be involved in the aetiology of Alzheimer's disease (AD). We describe the measurement of beta-NGF content in 4 regions of the cerebral cortex and the hippocampus in AD brain compared with brain tissue from age-matched normal subjects using a sensitive sandwich immunoassay (ELISA).

Latent herpes simplex virus type 1 in normal and Alzheimer's disease brains.

A viral aetiology has long been suspected for Alzheimer's disease (AD) but until now, techniques have not been sufficiently sensitive to provide clear evidence for or against the presence of any viral genome in AD brain. We have used the very highly sensitive method of polymerase chain reaction to look for herpes simplex virus type 1 (HSV1) DNA, specifically the viral thymidine kinase (TK) gene, in autopsy brain specimens. DNA-samples from HSV-infected and uninfected Vero cells have been examined concurrently to provide standard "HSV-positive" and "HSV-negative" samples, the latter guarding also against false positives caused by cross-contamination.

Low affinity nerve growth factor receptor binding in normal and Alzheimer's disease basal forebrain.

The binding characteristics of radiolabelled beta-nerve growth factor ([125I]NGF) have been determined on membrane preparations of basal forebrain from Alzheimer's disease (AD) brain and age-matched normal brains. [125I]NGF binds in a specific fashion indicative of a single receptor and is not displaced with microM concentrations of cytochrome c, insulin or epidermal growth factor (EGF). The mean dissociation constant (Kd) and the mean capacity (Bmax) of the NGF receptor were not significantly different between the 5 AD and 5 normal basal forebrain samples examined.

Comparison of three silver stains for demonstrating neurofibrillary tangles and neuritic plaques in brain tissue stored for long periods.

Three methods were compared to find a reliable method for demonstrating neurofibrillary tangles (NFTs) and neuritic plaques (NPs) in brain tissue stored for long periods in formalin or as paraffin blocks. The short-term fixation of tissue, e.g.

Pharmacokinetics of tacrine hydrochloride in Alzheimer's disease.

The clinical pharmacokinetics of tacrine hydrochloride have been characterized in patients who have Alzheimer's disease. Serum concentrations of the drug and of its probable metabolite were monitored in eight patients after a 25 mg oral dose, in six patients after a 50 mg oral dose, in four patients after repeated administration of 50 mg, and in two patients after a small intravenous dose. Urinary excretion of drug and metabolite for 24 hours was measured in one of the patients who received a small intravenous dose.

Distribution of beta-nerve growth factor receptors in the human basal forebrain.

The distribution of neurons expressing the receptor for beta-nerve growth factor has been examined immunohistochemically in serial coronal sections of basal forebrain from aged normal human subjects. Neurons expressing the receptor were observed in the nucleus of the diagonal band of Broca and in the anterior, the intermediate, and the posterior portions of the nucleus basalis of Meynert. Neurons could also be seen in the medial septal nucleus and embedded in myelinated fibre tracts such as those of the external capsule, cingulum, medullary laminae of the globus pallidus, ansa penduncularis, ansa lenticularis, and anterior commissure.

Clinical experience with and side-effects of tacrine hydrochloride in Alzheimer's disease: a pilot study.

Pharmacological manipulation of central cholinergic neurotransmission may prove beneficial in the treatment of Alzheimer's disease (AD). Tacrine hydrochloride is a central anticholinesterase which has been said to improve intellectual function in patients with AD. We report here our clinical experience with this drug in eight patients with AD, diagnosed according to DSM III and NINCDS-ADRDA criteria.

Recommended minimum data to be collected in research studies on Alzheimer's disease. The MRC (UK) Alzheimer's Disease Workshop Steering Committee.

In order to be able to compare the results of research work carried out in different centres on Alzheimer's disease and dementia, it is necessary for there to be standardised assessment methods. The Medical Research Council organised a workshop in order to see whether workers in Britain in the field of dementia research could agree on such standardised assessment methods. The workshop agreed guidelines for the minimum data which should be collected, in clinical and pathological studies, on patients with presumed Alzheimer's disease and dementia.

Nerve growth factor receptor mRNA distribution in human brain: normal levels in basal forebrain in Alzheimer's disease.

Nerve growth factor (NGF) receptor mRNA was found to be widely distributed throughout the human central nervous system, with the highest levels in the basal forebrain; this suggests that NGF may function as a retrograde trophic messenger for basal forebrain magnocellular cholinergic nerve cells. The degeneration of the latter constitutes one of the main features of Alzheimer's disease and it may be responsible for some of the cognitive impairment that characterizes the disease. No evidence was obtained for an insufficient synthesis of NGF receptor mRNA in the basal forebrain in Alzheimer's disease, where NGF receptor-like immunoreactivity was confined to neuronal cell bodies.

Kaposi's sarcoma in Zimbabwe. II. Peripheral lymphocytes, immunoglobulin G levels and HIV antibody positivity.

Patients with Kaposi's Sarcoma (KS) were grouped according to their clinical symptoms into "indolent", "locally aggressive", "endemic generalised aggressive" and "epidemic generalised aggressive" disease. Only the patients in the epidemic generalised aggressive disease group had serum antibodies to HIV. Complete peripheral blood counts, including lymphocyte subsets, and serum IgG assays were performed on all patients before treatment was initiated.

Clostridium difficile in acute and long-stay elderly patients.

A recent report suggested that Clostridium difficile (Cl. difficile) was endemic in chronic-care facilities. We have examined the prevalence of Cl.

Morphometric immunochemical analysis of neurons in the nucleus basalis of Meynert in Alzheimer's disease.

In Alzheimer's disease there is a reported loss of large cells in the cholinergic nucleus basalis of Meynert. It has been suggested, however, that there may be neurons in the nucleus basalis in Alzheimer's disease which are atrophied and therefore difficult to distinguish from neuroglia by size. This has important therapeutic implications and we have attempted to clarify the situation using a neuron-specific antiserum directed against neuron-specific enolase (NSE).

The differential involvement of subcortical nuclei in senile dementia of Alzheimer's type.

Cell counts have been performed on cholinergic subcortical nuclei, dorsal raphe nucleus, and locus caeruleus from up to 18 cases of Alzheimer's disease and 10 age-matched control subjects. In general, the extent of cell loss in these structures was similar. In the basal nucleus the anteromedial subdivision was the least, and the posterior subdivision the most affected.

Recent research into dementia.

In this paper, recent advances in the understanding of Alzheimer's disease that are relevant to the practising physician are reviewed, and an attempt is made to give researchers into Alzheimer's disease an overview into research areas other than their own. The fields covered include clinical presentation and investigation, neurochemistry, neuropathological abnormalities, immunological and viral aspects of aetiology and approaches to treatment.

Cholinesterase activities in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

Acetylcholinesterase (AChE) and nonspecific cholinesterase (nsChE) activities of lumbar ceresbrospinal fluid (CSF) from patients with a clinical or histological diagnosis of Alzheimer's disease have been compared with those of normal age-matched control patients and patients with dementia of non-Alzheimer aetiology. No significant differences in the AChE activity of lumbar CSF from histologically and clinically diagnosed Alzheimer's disease patients and normal age-matched controls were found, although they could be distinguished from controls and other dements by their lower lumbar CSF levels of nsChE activity and by their elevated ratio of AChE/nsChE. A lower level of AChE activity was observed in the lumbar CSF of patients with dementia of non-Alzheimer aetiology.