lzheimer’s disease (AD) is one of the most devastat-ing and costly disorders affecting the aging population.This disease has an estimated prevalence of up to 40%
inthose over age 80.1 Its
financial cost to society has beenestimated at between $70 and $100 billion annually.2Currently approved therapies, arguably modest in
effect,focus on symptomatic treatment.3-5 Preventive
strategies,on the other hand, remain elusive. Better understandingof this disorder, as well as the development of
both pre-ventive and improved symptomatic treatments, has
beenlimited by difficulties encountered in clinical diagnosisand the lack of adequate quantitative biomarkers for
thedisease.Clinical diagnosis depends on the definition of cognitivedeficits and the separation of normal age-related declinefrom pathological deterioration. Because the normal
rangeof variability of cognitive abilities among the aged isextremely large, it is difficult to quantify precise
normativelimits of the normal range. It is commonly understood
thatdifferent levels of cognitive functioning are expected
froma 90 year old than a 60 year old, or a university
graduateversus an illiterate person. Instead, the
clinical diagnosis ofdementia usually relies on the characterization of intra-individual decline from premorbid level of functioning.Typically, however, firm quantitative data
about premor-bid status are lacking, and the diagnostic process
reliesinstead on interviews at the time of symptomatic onset
thatattempt to characterize premorbid performance levels.Thisapproach is limited in its accuracy, and suffers
from possi-C l i n i c a l r e s e a r c h8 9Sensitivity and specificity of neuroimagingfor the diagnosis of Alzheimer’s
diseaseDaniel E. Wollman, MD, PhD; Isak
Prohovnik, PhDKeywords: Alzheimer’s
disease; dementia; neuroimaging; diagnosis; sensitivity; specificity;
CT; MRI; PET; SPECTAuthor affiliations: Department of Geriatrics, Mount Sinai School ofMedicine, New York, NY, USA (Daniel
E. Wollman); Departments of Psychiatryand Radiology, Mount Sinai School of Medicine, New York, NY, USA (IsakProhovnik); Department of Diagnostic
Radiology, Yale University, New Haven,CT, USA (Isak Prohovnik)Address for correspondence: Isak
Prohovnik, PhD, Bronx VAMC, 130 WestKingsbridge Road, Bronx, NY 10468,
USA (e-mail: isak.prohovnik@mssm.edu)AAlzheimer’s disease (AD) is one
of the most devastatingand costly disorders affecting the aging population.Structural imaging (computed tomography
[CT] and mag-netic resonance imaging [MRI]) and
functional imaging(single photon emission computed tomography
[SPECT]and positron emission tomography [PET])
have been eval-uated for their roles in the imaging
diagnosis of AD. Wehave reviewed the recent literature
to determine thecapabilities of these neuroimaging
techniques in com-parison to current standards of clinical
diagnosis. Ourresults indicate that there is wide
variability in the accu-racy of clinical assessments, in contrast
to a more limitedrange of variability of the accuracy
of neuroimaging mea-surements. These results suggest that
neuroimaging mayserve an adjunctive role in raising
this lower bound ofdiagnostic accuracy. Furthermore,
we suggest that neuro-imaging should be considered: (i)
when clinical expertiseis insufficient; (ii) as a complement
to specific likelihoodratios; and (iii) in specific types
of patients, for whom clin-ical evaluation is inappropriate or
inadequate.Dialogues Clin Neurosci.
2003;5:89-99.
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