Screening for dementia in primary care: a review of the use, efficacy and quality of measures.

BACKGROUND: Despite evidence that early identification of dementia is of growing policy and practice significance in the U.K., limited work has been done on evaluating screening measures for use in primary care. The aim of this paper is to offer a clinically informed synthesis of research and practice-based evidence on the utility, efficacy and quality of dementia screening measures. METHOD: The study has three elements: a review of research literature, a small-scale survey of measures employed in three primary care trusts, and a systematic clinical evaluation of the most commonly used screening instruments. The study integrates data from research and clinical sources. RESULTS: The General Practitioner Assessment of Cognition (GPCOG), the Memory Impairment Screen (MIS), and the Mini-Cognitive Assessment Instrument (Mini-Cog) were found to be brief, easy to administer, clinically acceptable, effective, and minimally affected by education, gender, and ethnicity. All three have psychometric properties similar to the Mini-mental State Examination (MMSE). CONCLUSIONS: Although the MMSE is widely used in the U.K., this project identifies the GPCOG, MIS and Mini-Cog as clinically and psychometrically robust and more appropriate for routine use in primary care. A coherent review of evidence coupled with an indepth evaluation of screening instruments has the potential to enhance ability and commitment to early intervention in primary care and, as part of a wider educational strategy, improve the quality and consistency of dementia screening.

Endotoxin-induced uveitis in the rat: observations on altered vascular permeability, clinical findings, and histology.

A single intraperitoneal dose of endotoxin (lipopolysaccharide or LPS) induces an acute inflammatory response in the uveal tract of rats. This inflammation is characterized by a breakdown of the blood/aqueous barrier within 3 hr after the LPS and the subsequent development of clinical disease and a cellular infiltrate. Early change in vascular permeability, clinical, and pathological changes were dose dependent with the two highest doses (100 micrograms or 500 micrograms) producing more severe pathology. Clinical and histopathologic abnormalities peaked at 24 hr and were resolving by 48 hr. Although clinical and histologic changes correlated well, the degree of breakdown of the blood/aqueous barrier at 3 hr failed to predict the extent of the cellular exudate measured by either clinical or histologic criteria. In addition, pharmacologic suppression of the early vascular permeability changes with indomethacin, cyproheptadine, or both agents failed to protect the animals consistently from subsequently developing significant clinical disease or cellular infiltrates on histopathology. LPS-induced uveitis in the rat provides a simple, reproducible model for ocular inflammation without requiring direct eye manipulation. The mediators responsible for the early vascular permeability in this model appear to be distinct from the mediators primarily responsible for the subsequent cellular exudate.

Rhodamine B as a test molecule in intraocular dynamics.

Rhodamine B is a lipid-soluble, nontoxic dye that fluoresces at longer wavelengths than fluorescein and consequently is detectable at lower concentrations in the ocular tissues. Its dynamics after topical and systemic administration are similar to those of lipid-soluble drugs.

Neural remodeling following experimental surgery of the rabbit cornea.

Wounding of the cornea results in extensive damage to the innervation that must be repaired to restore its normal structure and function. Four types of experimental wounds were produced in the corneas of young albino rabbits: 180 degrees penetrating perilimbal incisions, 4-mm central circular keratectomies and keratotomies, and radial keratotomies. Following perilimbal incisions, the denervated half of the cornea was reinnervated primarily by regenerating nerves that penetrated the limbal scar tissue. New neural growth from the innervated portion of the cornea provided a minor contribution to the denervated area. The regenerative response of the nerves following nonpenetrating procedures was found to be a biphasic process. In the first phase, a short period of degeneration of all nerves within the area enclosed by the wound boundary overlapped in time with the appearance of long, large caliber, dense neurites that coursed perpendicularly to the wound margins. The neurites originated from the intact subepithelial plexus at some distance from the wound margins. The second phase was initiated by the degeneration of the wound-oriented neurites and the concomitant appearance of a second generation of neurites. These new neurites originated from the transected stumps of the regenerating subepithelial axons at or near the wound margins. The oblique disposition of the second wave of neurites was similar to that of basal leashes in normal corneas. Nonpenetrating wounding procedures exhibited similar neural remodeling principles. In both types of keratotomies, nerve endings terminated within the wound in enduring and densely packed neuroma-like arrangements, while in keratectomies, nerve endings continued to grow toward the center of the cornea.

Endophthalmitis after penetrating keratoplasty.

Of 445 eyes (305 of which were aphakic) that underwent penetrating keratoplasty, 11 developed endophthalmitis, three immediately after surgery, two after subsequent secondary surgery, and six after late ulceration of the transplanted cornea. The diagnosis was based clinically on the loss of the red reflex and vitreous opacification, and was confirmed by culture of vitreous aspirate. All patients who developed endophthalmitis were aphakic and had received corticosteroids at the time of infection; most had undergone previous ocular surgery. These patients differed from those previously described with this condition because neither the donor tissue nor the storage medium was the source of infection. Treatment included intracameral, systemic, and topical administration of antibiotics. When the endophthalmitis originated from a corneal ulcer in a graft, the infected tissue was replaced with a new transplant. Despite treatment, the final visual outcomes were not good. One eye had a final visual acuity of 20/200 and one eye had a final visual acuity of 20/400. Three eyes had light perception and six eyes had no light perception. One eye was eventually enucleated.

Endothelial cell counts after epikeratophakia surgery.

We used specular microscopy to study the corneal endothelium of eight aphakic patients who had undergone epikeratophakia. The average post-operative period was 16 months with a range of 12 to 18 months. Corneal thickness increased from 0.52 mm +/- 0.01 mm to 0.88 mm +/- 0.04 mm with the addition of the onlay graft. The average pre-operative endothelial cell count was low (1,450 per mm2 +/- 218) and did not differ significantly (p greater than .9) from the average postoperative cell count (1,438 per mm2 +/- 218). Despite the increase in corneal thickness and low endothelial cell counts, we saw no corneal edema. We conclude that epikeratophakia is well tolerated by the cornea and can be performed safely on eyes that have already undergone substantial trauma to the endothelium.

Abnormal immune responses in the ocular presentation of Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome is an x-linked disorder characterized by a triad of thrombocytopenia, eczema, and recurrent infections. Until recently, survival into the second decade was rare. In the last few years, a better understanding of the syndrome has been achieved, and earlier recognition and newer modes of treatment have improved life. These patients are living longer and ophthalmologic presentation reflects this change. We present three case histories of patients followed for the past 15 years who have had, in association with this syndrome, eczema of the eyelids, episcleritis, marginal keratitis, and blepharitis.

Ocular albumin fluorophotometric quantitation of endotoxin-induced vascular permeability.

Bacterial endotoxin (lipopolysaccharide; LPS) is known to alter systemic vascular permeability, but this effect is difficult to monitor and quantitate in vivo. The ocular vessels of the rabbit are particularly sensitive to LPS. Using a slit lamp equipped with a fluorophotometer, we have adapted a method to quantitate endotoxin-induced ocular vascular permeability by measuring the accumulation of fluorescein isothiocyanate-conjugated albumin into the anterior chamber of the eye. After intravenous administration of Salmonella typhimurim LPS, the anterior chamber fluorescence and blood fluorescence were measured at intervals of 15 min and 1 h, respectively, over 4 h. In controls, maximal fluorescence in the anterior chamber was 3.1 +/- 0.8% of blood fluorescence. Doses of LPS as low as 0.25 mug/kg produced an ocular/serum fluorescence ratio of 17.6 +/- 4.9. A dose of 2.5 mug of LPS per kg tended to produce a higher ratio (68.0 +/- 7.1) than a larger dose of 50 mug/kg (30.5 +/- 16.6). Permeability changes began within 30 min after LPS, and the rate of dye accumulation varied over time, with maximal leakage usually occurring 90 min after LPS, but occasionally occurring much later. Repeated doses produced tolerance. By conjugating albumin to rhodamine and utilizing a second filter with the slit lamp to measure accumulation of this dye, we demonstrated the persistence of marked permeability during a period when intraocular fluorescein isothiocyanate and albumin levels were relatively constant. This methodology indicates that extremely low doses of LPS induce ocular permeability changes and that neither the time course nor the dose response of this effect is linear. Ocular fluorophotometry is a sensitive, noninvasive technique to study the dynamics and pharmacology of LPS-induced permeability changes.

Cardiac output following adrenomedullary deprivation.

This study was performed to determine whether or not the adrenal medulla supports cardiac output and total peripheral vascular resistance after acute hypovolemia. Two groups of anesthetized dogs were studied. The first group underwent right adrenalectomy and the second, left adrenal denervation in addition. Adrenocortical function, as reflected by compound F and dihydroepiandrosterone determinations, was equally maintained in both groups for 120 minutes after hemorrhage. Arterial plasma concentrations of norepinephrine and epinephrine were low in group 2, p greater than 0.05 to greater 0.01. Cardiac index and peripheral vascular resistance were comparable in both groups before and for two hours after the induction of hypovolemia to a mean arterial pressure of 50 millimeters of mercury. The findings indicate that cardiac output and total peripheral resistance do not require adrenomedullary catecholamine release after acute hypovolemia.