Every day for several months, mymother relived afresh the pain of learn-ing that my father had died. When doesa lapse of memory cease to be a trivialfailure of our brains capabilities andportend something far more serious? Ican remember when I was a sort of per-son. At what stage does the loss ofsharp recall rob us of speech, cut ourlinks with the rest of humanity?
These are urgent questions for ouraging society: estimates suggest thereare at least four million with Alzheim-ers disease in the U.S.; that numbercould grow fourfold over the next 30years. For many, the questions are cru-cial because several reversible condi-tionssuch as vitamin B12 deciency,thyroid disorders and some forms ofdepressionresemble Alzheimers.
A project called OPTIMA, undertakenat the Radclie Inrmary in Oxford, En-gland, may now be poised to bring pre-
cision to the identication of the dis-ease. Ever since Alois Alzheimer rstdescribed the condition in 1906, clini-cal diagnosis has depended on a psy-chiatric evaluation of the patient. Notsurprisingly, there is disagreement overdiagnoses, resulting in a failure to agreein up to a third of all cases. Even afterdeath, when an autopsy can be done,pathologists debate the dening crite-ria of Alzheimer-type brain changes.
Researchers with the OPTIMA project,however, claim they can identify thecondition in nearly all casesand longbefore the patient dies. The study ofmore than 350 people, both healthy aswell as those with memory decits, be-gan in 1988. Each subject spends oneday a year at the hospital for clinicalassessment and brain scanning; everysix months his or her memory and cog-nitive skills are assessed. Of the 115who have died, 110 have been autopsied.
The bottom line is that OPTIMA hasdemonstrated a way in which diagnosticaccuracy appears to be improved from65 to 97 percent and has simultaneous-ly oered a mechanism for making arobust physical measurement of the dis-eases advance. These results emergedfrom sets of sequential brain scans. Thesite of most disturbance in Alzheimersis the limbic systema brain regioncritically involved with emotion, motiva-tion and memory. An ordinary comput-ed tomographic (CT) scan failed to re-veal sucient detail of pathology in thissystem, but when they angled the scanat 20 degrees along the plane of the lim-bic system, project leaders David Smithand Kim A. Jobst found a far better pic-tureand their rst major insight.
They found that over a period ofyears, the size of the limbic system inAlzheimers patients diminished cata-strophicallythinning by as much as15 percent a year, 10 times the rate seenin healthy people. When it was seen inapparently unaected individuals, thisthinning was predictive. Using the CTscan alone increased specicity to 93percent. As these ndings became clear-er, the group began to look to othertypes of imaging.
Creating images of a brain at workhas long been a dream of neuroscien-tists. During recent years, positron emis-sion tomographic images of regions in-volved in reading or performing mathe-matical tasks have become icons ofpopular culture. The images show re-gions that are metabolically active ornot. Using a similar, but more widelyavailable imaging systemSPET (singlephoton emission tomography)thescientists were able to make additionalimages from their subjects brains.These scans revealed which areas wereworking and which were switched o.
Consistently in the Alzheimers pa-tients, the areas involved in languageskills as well as visual and spatial skillsappear to be less active. What was seenin the CT and SPET images was con-rmed in the autopsies. Combining theresults of both scans produces a diag-nosis with a false positive rate of only3 percent: the team seems to have ar-rived at a technique that can diagnoseAlzheimers disease at least ve yearsbefore death. Jobst and his colleaguessay they now want their methods to betested by other groups.
The signicance of the work lies part-ly in its sheer scale. OPTIMA has aunique databaseone that may be crit-ically useful when chemists and biolo-gists nd agents that might slow downor even reverse the progressive braindegeneration seen in this dehumaniz-ing disease. David Paterson
48 SCIENTIFIC AMERICAN June 1995
Employment Blues: Nothing to Do with Being Green
As the battle between jobs and the environment rages, at least one econ-omist says he has reason to call a truce. Eban S. Goodstein of SkidmoreCollege and the Economic Policy Institute in Washington, D.C., recently pub-lished his study tracking the number of jobs lost because of environmentallegislation. Using U.S. Department of Labor statistics from 1987 through1990, Goodstein found that for that period an average of only 0.1 percent ofall larger-scale layoffs nationwide were the result of environmental regula-tions, such as the Clean Air Actaccording to employers own estimates.Changes in a companys ownership, in contrast, accounted for almost 35times the number of jobs being terminated. Sasha Nemecek
Setting a StandardA British project produces a test for Alzheimers disease
PERCENT OF TOTAL JOB LOSS
Falling product demandContract completion
Business ownership changeBankruptcy
Labor-management disputeDomestic relocationModel changeoverImport competition
Weather-related curtailmentContract cancellation
Plant or machine repairsVacation period
Material shortagesOverseas relocation
Environment or safety relatedNatural disaster
Other (including reorganization)Not reported
0 5 10 15 20 25 30
Copyright 1995 Scientific American, Inc.