ORIGINAL CONTRIBUTION

Mild Cognitive Impairment

Clinical Characterization and Outcome
Ronald C. Petersen, PhD, MD; Glenn E. Smith, PhD; Stephen C. Waring, DVM, PhD;
Robert J. Ivnik, PhD; Eric G. Tangalos, MD; Emre Kokmen, MD

Background: Subjects with a mild cognitive impair- Auditory Verbal Learning Test. Clinical classifications
ment (MCI) have a memory impairment beyond that ex- of dementia and AD were determined according to the
pected for age and education yet are not demented. These Diagnostic and Statistical Manual of Mental Disorders,
subjects are becoming the focus of many prediction stud- Revised Third Edition and the National Institute of Neu-
ies and early intervention trials. rological and Communicative Disorders and Stroke–
Alzheimer’s Disease and Related Disorders Association
Objective: To characterize clinically subjects with MCI criteria, respectively.
cross-sectionally and longitudinally.
Results: The primary distinction between control sub-
Design: A prospective, longitudinal inception cohort. jects and subjects with MCI was in the area of memory,
while other cognitive functions were comparable. How-
Setting: General community clinic. ever, when the subjects with MCI were compared with
the patients with very mild AD, memory performance was
Participants: A sample of 76 consecutively evaluated similar, but patients with AD were more impaired in other
subjects with MCI were compared with 234 healthy con- cognitive domains as well. Longitudinal performance dem-
trol subjects and 106 patients with mild Alzheimer dis- onstrated that the subjects with MCI declined at a rate
ease (AD), all from a community setting as part of the greater than that of the controls but less rapidly than the
Mayo Clinic Alzheimer’s Disease Center/Alzheimer’s Dis- patients with mild AD.
ease Patient Registry, Rochester, Minn.
Conclusions: Patients who meet the criteria for MCI can
Main Outcome Measures: The 3 groups of individu- be differentiated from healthy control subjects and those
als were compared on demographic factors and mea- with very mild AD. They appear to constitute a clinical
sures of cognitive function including the Mini-Mental State entity that can be characterized for treatment interven-
Examination, Wechsler Adult Intelligence Scale– tions.
Revised, Wechsler Memory Scale–Revised, Dementia Rat-
ing Scale, Free and Cued Selective Reminding Test, and Arch Neurol. 1999;56:303-308

A
GREAT deal of interest Patients with an MCI are also becom-
has been generated con- ing of interest for treatment trials. The Alz-
cerning the topic of a heimer’s Disease Cooperative Study, which
boundary or transitional is a National Institute on Aging consor-
state between normal tium of Alzheimer’s Disease research
aging and dementia, or more specifi- groups, is embarking on a multicenter trial
cally, Alzheimer disease (AD). 1 This of agents intended to alter the progres-
condition has received several descrip- sion of patients with MCI to AD.6 Several
tors including mild cognitive impair- pharmaceutical companies are initiating
From the Departments of ment (MCI), incipient dementia, and large trials on this same group of indi-
Neurology (Drs Petersen and isolated memory impairment.2-4 Reviews viduals.
Kokmen), Health Sciences of several studies have indicated that Questions can be raised as to the
Research (Drs Petersen and
Waring), and Psychiatry and
these individuals are at an increased diagnostic criteria for MCI. Some inves-
Psychology (Drs Smith and risk for developing AD ranging from 1% tigators believe that virtually all these
Ivnik), and the Division of to 25% per year. 5 The variability in patients with mild disease have AD neu-
Community Internal Medicine these rates likely reflects differing diag- ropathologically, and, therefore, this
(Dr Tangalos), Mayo Clinic, nostic criteria, measurement instru- may not be a useful distinction.7 Oth-
Rochester, Minn. ments, and small sample sizes.5 ers6,8,9 note that while many of these pa-

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 SUBJECTS AND METHODS Free and Cued Selective Reminding Test,21-23 Boston Nam-
ing Test,24 Controlled Oral Word Association Test,25 and
category fluency procedures.26
The subjects for this study were recruited through the At the completion of this evaluation a consensus com-
Mayo Alzheimer’s Disease Center/Alzheimer’s Disease mittee meeting was held involving the behavioral neurolo-
Patient Registry (ADC/ADPR) using a standardized clini- gists, geriatrician, neuropsychologists, nurses, and other
cal protocol.8-12 The patients were derived from 2 sources: study personnel who had evaluated the patients. Diag-
community patients in Rochester, Minn, and regional noses were made for dementia and AD according to the Di-
patients referred to the ADC. The community patients agnostic and Statistical Manual of Mental Disorders, Revised
were recruited through the Division of Community Inter- Third Edition,27 and the National Institute of Neurological
nal Medicine of the Mayo Clinic from Rochester residents and Communicative Disorders and Stroke–Alzheimer’s Dis-
who were receiving their general medical care at the Mayo ease and Related Disorders of Association criteria, respec-
Clinic. If during the course of their medical evaluation the tively.28 The diagnosis of MCI was made if the patient met
patients expressed concern about their cognitive function, the following criteria: (1) memory complaint, (2) normal
the patients’ families expressed a concern about the activities of daily living, (3) normal general cognitive func-
patients’ cognition, or the examining physician detected a tion, (4) abnormal memory for age, and (5) not de-
cognitive change in the patients, the patient was then mented.8 Several studies3,8,9 characterizing the outcome of
referred to the ADC/ADPR staff. The regional patients patients with an MCI using these criteria have been re-
were derived from individuals who had come to the Mayo ported. At the conclusion of the consensus conference, af-
ADC for an evaluation of cognitive difficulties. These ter the diagnosis had been made, the patients were staged
individuals were either referred by their personal physi- on the Clinical Dementia Rating scale (CDR)29,30 and the
cians, family members, or by the patients themselves. Global Deterioration Scale.31
Patients from both the community and regional sources Control subjects were sought from the community
received an identical evaluation. On referral, the patients population of individuals receiving general medical exami-
were seen by a behavioral neurologist who obtained a medi- nations at the Mayo Clinic.32-34 They underwent a similar
cal history from the patient and corroborating sources, per- evaluation as the patients described earlier including the
formed the Short Test of Mental Status,13,14 Hachinski Is- neurologic examination and neuropsychological testing bat-
chemic Scale, 15 and a neurologic examination. Study tery. They qualified as controls if, in the opinion of their
personnel obtained other data including the Record of In- clinician, they were functioning normally in the commu-
dependent Living,16 Geriatric Depression Scale,17 and ad- nity and did not have a cognitive impairment. In addition,
ditional family history information. Laboratory studies were they could not have any active neurologic or psychiatric
performed, including a chemistry group, complete blood illnesses and could not be taking psychoactive medica-
cell count, sedimentation rate, vitamin B12 and folic acid tions. They could have comorbid illnesses such as hyper-
levels, sensitive thyroid-stimulating hormone level, and tension and coronary artery disease, and they could be tak-
syphilis serologic testing. All patients received a head ing medications for these disorders. However, in the opinion
imaging study (computed tomography or magnetic reso- of their physicians, these illnesses or their treatments did
nance imaging). Additional studies including a cerebro- not interfere with the patients’ cognitive function. These
spinal fluid analysis, electroencephalogram, and a single- patients were also reviewed at the consensus conference
photon emission computed tomographic scan were and CDR scale and Global Deterioration Scale ratings were
performed as the clinical situation indicated. completed.
Two sessions of neuropsychological testing were com- Patients and control subjects were reevaluated every
pleted on all subjects. The first set of tests was used for 12 to 18 months and received an abbreviated neuropsy-
diagnostic purposes and included the Wechsler Adult chological battery at that visit. Their performance was re-
Intelligence Scale–Revised, Wechsler Memory Scale– viewed at the consensus conference and the diagnoses were
Revised, Auditory Verbal Learning Test, and Wide-Range adjusted accordingly, if necessary. They were also reas-
Achievement Test-III.18 The second set of tests was used sessed on the CDR scale and the Global Deterioration Scale.
for research purposes and included the Mini-Mental State The Mayo ADC/ADPR projects have been approved by the
Examination (MMSE),19 Dementia Rating Scale (DRS),20 Mayo Institutional Review Board.

tients progress to AD, not all do, and consequently, the provide a background for the clinician to use in evalu-
distinction is important. ating these individuals in practice.
We have been enrolling patients at the mild end of
the cognitive spectrum for more than 10 years as part of RESULTS
a community study on aging and dementia.8,10 Our re-
cruitment scheme involves screening patients who are We have enrolled 76 subjects with the diagnosis of MCI
being seen by their primary care physicians for periodic over the last 11 years. The demographic features of these
general medical evaluations which affords us the oppor- subjects as well as groups of control subjects and pa-
tunity to detect patients before they present to a demen- tients with very mild AD enrolled over the same interval
tia or memory disorders clinic. This study reports the clini- grouped by CDR ratings are shown in the Table for com-
cal criteria used to diagnose these patients as well as their parison purposes. The Table also shows the perfor-
neuropsychological characterization, differentiation from mance of the 4 groups with respect to a sampling of cog-
controls and patients with mild AD, and the longitudi- nitive measures. As would be consistent with the selection
nal course of the subjects with MCI. As such, these data criteria, the subjects with MCI performed slightly more

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 poorly on these measures than the control subjects, but
were superior to the patients with AD. Statistical com- Comparison of 4 Clinical Groups
parisons in the Table were performed using a 1-way analy- on Various Cognitive Scales*
sis of variance with each cognitive measure as the de-
Controls, MCI, AD, AD,
pendent variable comparing the 4 groups of subjects. The CDR 0 CDR 0.5 CDR 0.5 CDR 1
relevant pairwise comparisons were made between ad-
N 234 76 48 58
jacent groups, eg, control vs MCI and MCI vs AD (CDR M/F 71/163 30/46 19/29 15/43
0.5) and AD (CDR 0.5) vs AD (CDR 1), using Tukey hon- APOE, e4/non e4 161/46 43/22 21/17 24/22
estly significant difference with a level of significance be- Age, y 79.8 ± 0.5a 80.9 ± 1.0a 75.6 ± 1.7c 80.5 ± 1.0a
ing set at the .01 level due to the large number of com- Education, y 13.3 ± 0.2a 13.7 ± 0.4a 12.5 ± 0.4b 12.1 ± 0.4b
parisons performed. CDR sum 0.0 ± 0.0a 1.5 ± 0.2b 3.3 ± 0.1c 5.9 ± 0.2d
As one measure of disease severity, the CDR sum of of boxes
GDS 1.1 ± 0.0a 2.7 ± 0.1b 3.4 ± 0.1c 3.9 ± 0.1d
box scores was calculated.29,30 The CDR sum of the box GDepS 2.1 ± 0.1a 2.8 ± 0.3b 3.2 ± 0.3b 3.4 ± 0.3b
scores was determined by totaling the individual box scores MMSE 28.3 ± 0.1a 26.0 ± 0.3b 22.6 ± 0.5c 21.4 ± 0.4c
for a given patient (range, 0-18). For example, a control DRS 134.3 ± 0.4a 124.7 ± 1.1b 112.7 ± 1.9c 106.7 ± 1.9c
patient may have had 0 in each of the 6 boxes for the vari- VIQ 102.5 ± 0.6a 99.1 ± 1.3a 86.6 ± 1.5b 85.4 ± 1.2b
ous categories. A typical patient with AD and a summary PIQ 100.4 ± 0.8a 96.2 ± 1.4b 82.1 ± 1.7c 81.4 ± 1.2c
CDR score of 1 might have had the sum of the 6 having FSIQ 101.8 ± 0.7a 98.0 ± 1.3a 83.9 ± 1.3b 83.0 ± 1.0b
BNT 50.3 ± 0.5a 45.0 ± 1.2b 34.7 ± 1.9c 33.5 ± 1.4c
scored 1 in each of the 6 individual boxes. This statistic
COWAT 35.1 ± 0.7a 29.9 ± 1.3b 24.4 ± 1.7b 20.0 ± 1.4b
yielded an approximate index of severity on the CDR as WMS-R
well as involvement of activities of daily living. LMI 21.3 ± 0.4a 12.7 ± 0.6b 8.6 ± 0.8c 5.8 ± 0.6d
On measures of general cognition such as the Wechs- LMII 15.3 ± 0.5a 4.2 ± 0.6b 2.8 ± 0.6b 1.5 ± 0.5b
ler Adult Intelligence Scale–Revised, the controls and sub- VRI 25.7 ± 0.4a 20.2 ± 0.7b 14.4 ± 0.9c 13.8 ± 0.7c
jects with MCI did not differ significantly. On the screen- VRII 17.6 ± 0.5a 7.4 ± 0.9b 4.1 ± 0.7c 2.2 ± 0.4d
AVLT
ing measures of general cognition, MMSE and DRS, there
LNG 35.5 ± 0.6a 25.0 ± 0.9b 21.5 ± 1.1c 17.8 ± 0.8d
were small differences largely due to the memory com- % RET 62.1 ± 1.6a 21.6 ± 2.9b 8.3 ± 2.8c 10.8 ± 3.1c
ponent of those measures. In general, while the subjects FCSRT
with MCI did not perform as well as the control sub- LN 58.4 ± 0.8a 34.1 ± 1.7b 25.6 ± 2.3c 16.6 ± 1.6d
jects, they still functioned in the normal range. How- % RETN 86.7 ± 1.1a 59.8 ± 4.4b 39.5 ± 6.2c 31.4 ± 5.3c
ever, the subjects with MCI differed from even the CDR
0.5 patients with AD on virtually all measures of general *Analyses reflect differences at the .01 level for comparison of adjacent
groups. Values are mean ± SD. CDR indicates Clinical Dementia Rating;
cognitive function (Figure 1). MCI, mild cognitive impairment; AD, Alzheimer disease; APOE, ratio of
The Table displays memory data among the 4 groups. apolipoprotein E e4 noncarriers to carriers excluding 2/4 genotypes;
Again, as would be expected from the selection criteria, GDS, Global Deterioration Scale; GDepS, Geriatric Depression Scale;
the subjects with MCI were significantly impaired on all MMSE, Mini-Mental State Examination; DRS, Dementia Rating Scale;
VIQ, Wechsler Adult Intelligence Scale, Verbal IQ; PIQ, Wechsler Adult
memory measures relative to control subjects and ap- Intelligence Scale, Performance IQ; FSIQ, Wechsler Adult Intelligence Scale,
peared similar to the patients with AD. These results were Full-Scale IQ; BNT, Boston Naming Test; COWAT, Controlled Oral Word
seen for virtually all measures of learning and delayed Association Test; WMS-R, Wechsler Memory Scale-Revised; LM, Logical
Memory; VRI, Visual Reproductions; AVLT, Auditory Verbal Learning Test;
recall using word lists, paragraphs, and nonverbal ma- LNG, sum of learning trials 1 to 5; %RET, delayed recall/trial 5 3 100;
terials. The differences were less dramatic between the FCSRT, Free and Cued Selective Reminding Test; LN, sum of the performance
subjects with MCI and the patients with AD; rather, the across trials 1 to 6; and RETN, delayed recall/trial 6 3 100. Comparison of 4
clinical groups on various cognitive scales. Analyses reflect differences at the
other areas of cognition and functional measures differ- .01 level for comparison of adjacent group. Similar letters (ie, a, b, c, and d)
entiated these groups. indicate no significant difference between pairwise comparisons.
The Boston Naming Test results paralleled those of
the memory domain. These findings can be interpreted
as indicating that either the linguistic function of nam- the patients with AD. Similarly, the subjects with MCI
ing is impaired early in the disease process, or that this showed a slower rate of change on the DRS and Global
naming test actually assesses semantic memory and there- Deterioration Scale with respect to annualized differ-
fore is consistent with the other memory data. ences than did the patients with AD.
Figure 2 demonstrates the outcome of the sub-
jects with MCI up to approximately 4 years of follow- COMMENT
up. The conversion rate was 12% per year for the 4 years.
These rates are in contrast to conversion rates for the This study was designed to quantitatively characterize and
healthy control subjects in our community sample. We describe the clinical course of patients diagnosed as hav-
have enrolled and followed up more than 500 control sub- ing MCI using criteria that are similar to those being adopted
jects in the 10 years of the study, and these subjects tend by several multicenter treatment trials. While the criteria
to convert to MCI/AD at a rate of approximately 1% to for MCI can be accepted by investigators in principle, the
2% per year. operationalization of these criteria can be challenging. As
Figure 3 shows the mean annualized rate of change such, these results provide cross-sectional and longitudi-
for all subjects in the comparison groups on the MMSE, nal data with respect to these criteria.
DRS, and Global Deterioration Scale. On the MMSE, the As expected, the subjects with MCI performed more
subjects with MCI behaved more like control subjects than similarly to the control subjects than the patients with

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 30 MMSE 110 Full-Scale IQ
105
100
20
95
90
10
85
80
0 75

16 Logical Memory II 18 Visual Reproductions II

14 16
12 14
12
10
10
8
8
6
6
4 4
2 2
0 0
Controls MCI AD AD Controls MCI AD AD
CDR 0 0.5 0.5 1 CDR 0 0.5 0.5 1

Figure 1. Relative performance among 4 groups: controls, subjects with mild cognitive impairment (MCI) (Clinical Dementia Rating [CDR] 0.5), and patients with
Alzheimer disease (AD) (CDR 0.5; CDR 1), on measures of global cognitive functioning, Mini-Mental State Examination (MMSE), and full-scale IQ compared with
performance on measures of delayed recall for verbal materials (Logical Memory II) and nonverbal materials (Visual Reproductions II).

MCI Alzheimer Disease 0 MMSE

100
–1
80
–2
60
MCI, %

40 –3

20 –4

0
Initial Examination 12 24 36 48 2 Dementia Rating Scale
mo 0
–2
Figure 2. Annual rates of conversion from mild cognitive impairment (MCI)
to dementia over 48 months. –4
–6
–8
AD on measures of general cognition and other non- –10
memory indexes. While there may have been mild –12
impairments in some of the domains of cognition, eg,
full-scale IQ, the actual raw score difference was suffi- 1.0 Global Deterioration Scale
ciently small, eg, a full-scale IQ of 101.8 vs 98.0 for
0.8
controls and subjects with MCI, respectively, to not be
clinically meaningful. That is, it is doubtful that most 0.6
clinicians would say that a subject with a full-scale IQ 0.4
of 98 was demented on the basis of this measure. The
subjects with MCI performed more poorly than the 0.2

control subjects on the Controlled Oral Word Associa- 0.0

tion Test, but once again, the performance of the sub- Controls MCI AD AD
CDR 0 0.5 0.5 1
jects with MCI was in the normal range for age based
on our community studies.35 This is not to say, how- Figure 3. Annual rates of change on 3 measures of global function for
ever, that these subjects may not have incipient clinical controls, subjects with mild cognitive impairment (MCI) (Clinical Dementia
AD; rather, most clinicians would be reluctant to make Rating [CDR] 0.5), and patients with Alzheimer disease (AD) (CDR 0.5;
CDR 1). MMSE indicates Mini-Mental State Examination.
the diagnosis of AD at this stage. In addition, it is not
likely that these subjects have a significant functional
deficit since their mean CDR sum of box scores was 1.5 From a memory perspective, the subjects with MCI
with most of the decline being accounted for by appeared more like the patients with AD than the con-
memory deficits. However, the patients with very mild trol subjects. Again, this is not surprising considering the
AD (CDR 0.5) had a mean CDR sum of the box score of selection criteria, but these data lend quantitation to these
3.3 that reflected these subjects’ impairment in func- criteria. In fact, if the clinician sees a patient with im-
tional domains. paired delayed recall performance or difficulty benefit-

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 ing from semantic cues during learning or recall in the SD below healthy subjects on Verbal IQ, Performance IQ,
setting of relatively preserved general cognition, the di- MMSE, and DRS) and are functionally impaired (CDR sum
agnosis of MCI should be entertained. of boxes, Global Deterioration Scale). These individuals meet
Most of the subjects received the diagnosis of MCI the criteria for very mild AD and are distinguishable from
at entry into the study, while a few of the subjects had the subjects with MCI.
converted from a prior normal control status. The docu- All the classifications discussed are clinical. While
mentation of a memory decline was largely historical and the diagnoses are supported by neuropsychological data,
based on the interview with the subject. With respect to the ultimate judgment is that of a clinician. Most clini-
the quality of the memory complaints, we asked for cians would be uncomfortable at classifying subjects with
changes in memory function with respect to items in- MCI as having AD based on the criteria described.
volving recent memory. We prefer corroboration by an The rates of change of subjects with MCI are differ-
informant who knows the patient well. Previous work36 ent from control subjects and patients with AD. It is note-
has indicated that while individuals’ subjective impres- worthy that the control subjects improved from baseline
sions of their memory function correlate best with in- to first follow-up on the full-scale IQ, which is a docu-
dexes of depression, informants’ assessments correlate well mented phenomenon.42 This makes the decline of the MCI
with objective performance. group meaningful, albeit small. These subjects change on
Since the memory decline was subjective, it was nec- the global instruments more rapidly than control subjects
essary to corroborate memory performance as being ab- but not as rapidly as the clinically diagnosed patients with
normal (generally 1.5 SD below age- and education- AD. This could reflect several factors. It is possible that the
matched control subjects) while general cognitive (Verbal measuring instruments are not linear and are less sensi-
IQ, Performance IQ) was within 0.5 SD of appropriate tive to changes in the more mild states. It is also possible
controls. The value of availability of an objectively docu- that the MCI group is “contaminated” with essentially
mented decline in performance is helpful in detecting healthy subjects who are not going to progress to AD. This
those subjects who are predisposed to develop AD.37 difference can also be used to argue that not all subjects
The clinical course of these subjects is important to with MCI have AD at this point in time.
describe. Individuals with MCI appear to be at an in- As is apparent, there are many interesting ques-
creased risk of developing AD at the rate of 10% to 12% tions surrounding subjects with MCI. This study was de-
per year. As Dawe et al5 have indicated, there is variabil- signed to lend quantitative characterization to the clini-
ity in the literature largely due to different clinical cri- cal criteria for MCI that are being used in several
teria, neuropsychological measures used, and small num- multicenter trials. It also documents the clinical course
bers of subjects. However, several recent studies1,8,38,39 of these subjects over the years with respect to their
using somewhat similar criteria, neuropsychological mea- changes on standard instruments and their diagnostic out-
sures, and larger subject pools have demonstrated rates comes. These results demonstrated that these subjects are
that are consistent with those reported herein. at increased risk of progressing to AD and are useful to
Our previous work demonstrated that apolipopro- characterize for both theoretical and practical purposes.
tein E e4 carrier status and features of memory function
may predict who is likely to progress to AD more rap- Accepted for publication October 7, 1998.
idly.3,8,12,38,40 Magnetic resonance imaging volumetric This study was supported by grants AG06786 and
measurements of the hippocampal formation may also AG08031 from the National Institute on Aging, Bethesda, Md.
be useful.41 We thank Ruth Cha, MS, for statistical assistance and
There are 2 issues with respect to the classification Jackie Evans for secretarial expertise. We also thank the staff
of MCI and CDR 0.5 that need to be clarified. The first of the Mayo Alzheimer’s Disease Center and the Mayo Alz-
issue pertains to potential contamination of the MCI di- heimer’s Disease Patient Registry, Rochester, Minn, for evalu-
agnosis with healthy individuals. As described earlier, it ation and care of patients.
is possible that some subjects with MCI may have had Reprints: Ronald C. Petersen, PhD, MD, Department
long-standing poor memory function that may not of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN
progress. While the proportion of the total group of sub- 55905.
jects with MCI who constitute long-standing poor per-
formers is small, without longitudinal objective data, some REFERENCES
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 LETTERS TO THE EDITOR

associations between anticardiolipin antibodies and intra-

Anticardiolipin Antibodies cranial hypertension. We appologize for our failure to cite
their work that was published after our manuscript was
completed but prior to its submission to the ARCHIVES.

I n their article on the prevalence of anticardiolipin

antibodies in patients with idiopathic intracranial
hypertension, Leker and Steiner 1 state that “the in-
cidence of anticardiolipin antibodies in idiopathic intra-
cranial hypertension has not been systematically stud-
According to Howell, Sussman et al included patients with
dural sinus thrombosis in their series whereas such patients
were not included in our series. Moreover, dural sinus
thrombosis may present in a benign fashion mimicking
ied... .” Obviously they were unaware of work carried out benign intracranial hypertension (pseudotumor cerebri).2
at this institution.2 Sussman and colleagues 3 looked for Neuroimaging studies, which are mandatory for the diag-
abnormalities of coagulation in 38 patients with the syn- nosis of dural sinus thrombosis, are not reported for their
drome of idiopathic intracranial hypertension and found patients and therefore, the true incidence of benign intra-
evidence of antiphospholipid antibodies (anticardio- cranial hypertension in the series of Sussman et al is
lipin antibody and/or lupus anticoagulant) in 12 cases unknown. Nevertheless, these 2 studies provide support to
(32%), in 1 of 18 healthy obese controls, and 3 of 24 con- the association of anticardiolipin antibodies with intracra-
trols with other neurologic disease. The patients were simi- nial hypertension.
lar, but not identical in the 2 studies. Only 18 of the pa- We concur with Howell that further studies investi-
tients studied by Sussman and colleagues had had imaging gating this association should be conducted before manage-
of the intracranial venous system (angiography) and 3 ment issues can be answered.
had evidence of dural sinus thrombosis and would have
been excluded from the series reported by Leker and Ronen R. Leker, MD
Steiner. Nevertheless, the results obtained by Leker and Israel Steiner, MD
Steiner are remarkably similar to the earlier study, with Department of Neurology
6 of their 14 patients having positive anticardiolipin an- Hadassah Medical Center
tibody, and although the rates of positivity in suitable con- Ein Kerem, PO Box 12000
trols from the same population are not provided, this sec- Jerusalem 91120, Israel
ond study is further evidence that this is a real association 1. Sussman J, Leach M, Greaves M, Malia R, Davies-Jones GAB. Potentially pro-
and warrants further investigation. We need to deter- thrombotic abnormalities of coagulation in benign intracranial hyperten-
sion. J Neurol Neurosurg Psychiatry. 1997;62:229-233.
mine how persistent antiphospholipid antibodies are in 2. Ameri A, Bousser MG. Cerebral venous thrombosis. Neurol Clin. 1992;10:87-111.
these patients, their relationship to prognosis, their re-
lationship with other possible risk factors (the non-
obese patients may be more likely to have antiphospho- Correction
lipid antibodies3) and whether they affect the response
to treatments, both those conventionally used for idio-
pathic intrcranial hypertension and those used for other Error of Figure. In the study titled “Mild Cognitive
antiphospholipid antibody syndromes. Impairment: Clinical Characterization and Outcome” by
Petersen et al published in the March issue of the ARCHIVES
(1999;56:303-308), the bottom panel of Figure 3 was
Stephen J. L. Howell, DM, FRCP
incorrect. The correct version of the bottom panel of the
Royal Hallamshire Hospital figure is reprinted here.
The Central Sheffield University Hospitals
North Trent Institute of Neuroscience
1.0 Global Deterioration Scale
Glossop Rd
Sheffield S10 2JF, England
0.8
1. Leker L, Steiner I. Anticardiolipin antibodies are frequently present in patients
with idiopathic intracranial hypertension. Arch Neurol. 1998;55:817-820.
2. Sussman JD, Davies-Jones GAB, Greaves M, Leach M. Coagulation abnor- 0.6
malities in benign intracranial hypertension. J Neurol Neurosurg Psychiatry.
1993;56:724.
3. Sussman J, Leach M, Greaves M, Malia R, Davies-Jones GAB. Potentially pro-
0.4
thrombotic abnormalities of coagulation in benign intracranial hyperten-
sion. J Neurol Neurosurg Psychiatry. 1997;62:229-233.
0.2

In reply
0.0
We thank Howell for his comments regarding our article. Controls MCI AD AD
CDR 0 0.5 0.5 1
Indeed, the series published by Sussman et al1 adds impor-
tant information to our knowledge concerning possible

ARCH NEUROL / VOL 56, JUNE 1999

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