Reductions in regional cerebral perfusion, particularly in the posterior temporo-parietal lobes, are well recognized in Alzheimer's disease. We set out to correlate perfusion changes, using (99m)Tc-HMPAO single photon emission tomography (SPET), with the pathological stage of Alzheimer's disease. The 'Braak stage' of the distribution of neurofibrillary pathology in post-mortem brains was used to classify SPET scans taken in life from a mixed (dementia and control) elderly population into the entorhinal stage (n = 23 subjects), limbic stage (n = 30 subjects) and neocortical stage (n = 36 subjects) Alzheimer's disease pathology. The SPET scans were then registered to a common, standard Talaraich space, and single template scans produced for each pathological stage. Comparison of these templates revealed an evolution in the pattern of reduction in regional perfusion. Additional comparisons were performed using earlier SPET scans obtained 5 years before death. For comparisons between templates, a threshold of 10% perfusion change was chosen so as to be clinically relevant as well as statistically significant. Reduced perfusion appears between the entorhinal and limbic stages in the anterior medial temporal lobe, subcallosal area, posterior cingulate cortex, precuneus and possibly the supero-anterior aspects of the cerebellar hemispheres. Large posterior temporo-parietal perfusion defects then appear between the limbic and neocortical stages, before finally large frontal lobe perfusion defects. The time course of these perfusion defects appears relatively long, suggesting that perfusion changes may have scope to be a diagnostic aid in staging Alzheimer's disease in life. The reduction in anterior medial temporal lobe perfusion may have future relevance on modern high resolution SPET and PET systems and also perfusion-type MRI sequences.

A combination of medial temporal lobe atrophy, shown by computed tomography, and reduced blood flow in the parietotemporal cortex, shown by single photon emission tomography, was found in 86% (44151) of patients with a clinical

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SummarySodium hyaluronate solutions have been advocated in the management of a variety of dry-eye states. By virtue of their non-Newtonian rheological properties, for mulations exhibiting high zero-shear viscosities may be used as an artificial tear with the expectation of prolonged precorneal residence times and improved tolerance.Quantitative gamma scintigraphy was used to evaluate the residence times of 0.2% and 0.3% sodium hyaluronate solutions and a polymer-free solution of buffered saline in 12 patients with keratoconjunctivitis sicca and a group of six normal volun teers. Using several indices of residence time, mean values for the sodium hyalur. onate solutions were significantly longer than those for buffered saline. Parallel changes in tear film thickness were also demonstrated using a technique based on laser interferometry.Although a variety of therapeutic strategies can be utilised in the management of dry-eye disorders,1.2 the basis of therapy remains the artificial tear. The principal limitation of currently available tear substitutes is the short duration of symptom control experienced by some patients. A number of approaches have, therefore, been adopted to prolong the time they remain in contact with the ocular surface including the use of high viscosity formula tions,"· slow-release artificial tears' and occlusion of the lacrimal puncta.1> However, none of these methods have met with uniform success.Polymer solutions formulated at high vis cosity have longer residence times, 7 .H but are poorly tolerated because of transmitted 'University of Oxford, Department of Ophthalmology.shearing forces associated with blinking and rapid eye movements. It is in this respect that formulations of polymers that display non Newtonian or pseudoplastic properties offer a potential therapeutic advantage over conven tional artificial tears. At concentrations of 0. 2% and 0.3% , sodium hyaluronate solu tions exhibit high static. or zero-shear, vis cosities but undergo dramatic reduction in viscosity with increasing shear rate� (Fig. 1), thereby offering significantly less resistance to the movement of the lid over the globe than viscous Newtonian formulations. It is the expectation of prolonged residence time asso ciated with high zero-shear viscosities, and of patient acceptance owing to its shear-thinning behaviour, that has lead to the investigation of

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