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Every day for several months, my mother relived afresh the pain of learn- ing that my father had died. When does a lapse of memory cease to be a trivial failure of our brains capabilities and portend something far more serious? I can remember when I was a sort of per- son. At what stage does the loss of sharp recall rob us of speech, cut our links with the rest of humanity? These are urgent questions for our aging society: estimates suggest there are at least four million with Alzheim- ers disease in the U.S.; that number could grow fourfold over the next 30 years. For many, the questions are cru- cial because several reversible condi- tionssuch as vitamin B 12 deciency, thyroid disorders and some forms of depressionresemble Alzheimers. A project called OPTIMA, undertaken at 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 rst described the condition in 1906, clini- cal diagnosis has depended on a psy- chiatric evaluation of the patient. Not surprisingly, there is disagreement over diagnoses, resulting in a failure to agree in up to a third of all cases. Even after death, 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 the condition in nearly all casesand long before the patient dies. The study of more than 350 people, both healthy as well as those with memory decits, be- gan in 1988. Each subject spends one day a year at the hospital for clinical assessment and brain scanning; every six months his or her memory and cog- nitive skills are assessed. Of the 115 who have died, 110 have been autopsied. The bottom line is that OPTIMA has demonstrated a way in which diagnostic accuracy appears to be improved from 65 to 97 percent and has simultaneous- ly oered a mechanism for making a robust physical measurement of the dis- eases advance. These results emerged from sets of sequential brain scans. The site of most disturbance in Alzheimers is the limbic systema brain region critically involved with emotion, motiva- tion and memory. An ordinary comput- ed tomographic (CT) scan failed to re- veal sucient detail of pathology in this system, but when they angled the scan at 20 degrees along the plane of the lim- bic system, project leaders David Smith and Kim A. Jobst found a far better pic- tureand their rst major insight. They found that over a period of years, the size of the limbic system in Alzheimers patients diminished cata- strophicallythinning by as much as 15 percent a year, 10 times the rate seen in healthy people. When it was seen in apparently unaected individuals, this thinning was predictive. Using the CT scan alone increased specicity to 93 percent. As these ndings became clear- er, the group began to look to other types of imaging. Creating images of a brain at work has 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 of popular culture. The images show re- gions that are metabolically active or not. Using a similar, but more widely available imaging systemSPET (single photon emission tomography)the scientists were able to make additional images from their subjects brains. These scans revealed which areas were working and which were switched o. Consistently in the Alzheimers pa- tients, the areas involved in language skills as well as visual and spatial skills appear to be less active. What was seen in the CT and SPET images was con- rmed in the autopsies. Combining the results of both scans produces a diag- nosis with a false positive rate of only 3 percent: the team seems to have ar- rived at a technique that can diagnose Alzheimers disease at least ve years before death. Jobst and his colleagues say they now want their methods to be tested by other groups. The signicance of the work lies part- ly in its sheer scale. OPTIMA has a unique databaseone that may be crit- ically useful when chemists and biolo- gists nd agents that might slow down or even reverse the progressive brain degeneration seen in this dehumaniz- ing disease. David Paterson 48 SCIENTIFIC AMERICAN June 1995 Employment Blues: Nothing to Do with Being Green A s 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 Skidmore College and the Economic Policy Institute in Washington, D.C., recently pub- lished his study tracking the number of jobs lost because of environmental legislation. Using U.S. Department of Labor statistics from 1987 through 1990, Goodstein found that for that period an average of only 0.1 percent of all larger-scale layoffs nationwide were the result of environmental regula- tions, such as the Clean Air Act—according to employers’ own estimates. Changes in a company’s ownership, in contrast, accounted for almost 35 times the number of jobs being terminated. Sasha Nemecek Setting a Standard A British project produces a test for Alzheimers disease PERCENT OF TOTAL JOB LOSS REASON Seasonal work Falling product demand Contract completion Business ownership change Bankruptcy Labor-management dispute Domestic relocation Model changeover Import competition Weather-related curtailment Contract cancellation Plant or machine repairs Vacation period Material shortages Overseas relocation Automation Energy-related disruption Environment or safety related Natural disaster Other (including reorganization) Not reported 0 5 10 15 20 25 30 Copyright 1995 Scientific American, Inc.

Employment Blues: Nothing to do with being Green

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Every day for several months, my

mother relived afresh the pain of learn-

ing that my father had died. When doesa lapse of memory cease to be a trivialfailure of our brainÕs 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-erÕs disease in the U.S.; that numbercould grow fourfold over the next 30years. For many, the questions are cru-cial because several reversible condi-tionsÑsuch as vitamin B12 deÞciency,thyroid disorders and some forms ofdepressionÑresemble AlzheimerÕs.

A project called OPTIMA, undertakenat the RadcliÝe InÞrmary in Oxford, En-gland, may now be poised to bring pre-

cision to the identiÞcation of the dis-ease. Ever since Alois Alzheimer Þrstdescribed 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 deÞning crite-ria of Alzheimer-type brain changes.

Researchers with the OPTIMA project,however, claim they can identify thecondition in nearly all casesÑand longbefore the patient dies. The study ofmore than 350 people, both healthy aswell as those with memory deÞcits, 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 oÝered a mechanism for making arobust physical measurement of the dis-easeÕs advance. These results emergedfrom sets of sequential brain scans. Thesite of most disturbance in AlzheimerÕsis the limbic systemÑa brain regioncritically involved with emotion, motiva-tion and memory. An ordinary comput-ed tomographic (CT) scan failed to re-veal suÛcient 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-tureÑand their Þrst major insight.

They found that over a period ofyears, the size of the limbic system inAlzheimerÕs patients diminished cata-strophicallyÑthinning by as much as15 percent a year, 10 times the rate seenin healthy people. When it was seen inapparently unaÝected individuals, thisthinning was predictive. Using the CTscan alone increased speciÞcity to 93percent. As these Þndings 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 systemÑSPET (singlephoton emission tomography)Ñthescientists were able to make additionalimages from their subjectÕs brains.These scans revealed which areas wereworking and which were Òswitched oÝ.Ó

Consistently in the AlzheimerÕs 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-Þrmed 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 diagnoseAlzheimerÕs disease at least Þve yearsbefore death. Jobst and his colleaguessay they now want their methods to betested by other groups.

The signiÞcance of the work lies part-ly in its sheer scale. OPTIMA has aunique databaseÑone that may be crit-ically useful when chemists and biolo-gists Þnd agents that might slow downor even reverse the progressive braindegeneration seen in this dehumaniz-ing disease. ÑDavid 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 Skidmore

College 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 Act—according to employers’ own estimates.Changes in a company’s ownership, in contrast, accounted for almost 35times the number of jobs being terminated. —Sasha Nemecek

Setting a StandardA British project produces a test for AlzheimerÕs disease

PERCENT OF TOTAL JOB LOSS

REASON

Seasonal workFalling product demand

Contract completionBusiness ownership change

BankruptcyLabor-management dispute

Domestic relocationModel changeoverImport competition

Weather-related curtailmentContract cancellation

Plant or machine repairsVacation period

Material shortagesOverseas relocation

AutomationEnergy-related disruption

Environment or safety relatedNatural disaster

Other (including reorganization)Not reported

0 5 10 15 20 25 30

Copyright 1995 Scientific American, Inc.