Prohovnik edited recently with four on
Edwards AL: Experimental Design in Psy-
articles on CBF in normal subjects
(including one by himself entitled "Ob¬
servations on the Functional Signifi¬
cance of Regional Cerebral Blood Flow
in Resting Normal Subjects"), no men¬
tion was made of the exclusion of psy¬
chiatric illnesses.1 We assume that ex¬
clusion of physical and psychiatric
illnesses were the criteria they used
for defining normality, as we did. We
stated in our report (p 1122) that the
principal investigator (a board-cer¬
tified psychiatrist) interviewed both
the patients and control subjects. The
control subjects (volunteers) were free
of all physical and psychiatric illness.
The criticisms made about the CBF
index we used can only be explained by
their unfamiliarity with the US litera¬
ture. This index was developed by the
Harshaw Chemical Company, Cleve¬
land, in collaboration with Dr John S.
Meyer, who has published extensively
on the subject. A review of the CBF
research conducted with this index
would be beyond the scope of this com¬
munication. The only single-authored
textbook on the inhalation technique
where both normal and abnormal
values are given and a report on the
responsivity of this index to PEco2
changes are referenced.2,3 The latter
reference obviates the need to specu¬
late whether this index "behaves as the
ISI2 does."
The statements made about CBF
and PEco2 are difficult to comprehend.
Prohovnik et al reiterated our dis¬
cussion and provided two additional
references on the PEco2-induced
changes in CBF as measured by the
xenon XE 133 inhalation technique.
These studies and several others3 were
not mentioned in our report as the
topic was not CBF and C02. Yamamoto
et al ( =
65; mean age, 52 years; range,
35 to 72 years) found an age-related
decline in CBF responsivity to C02,
while Maximilian and associates
(N 10;
= mean age, 26 ±4 years)
ported a correction factor of 3.2% CBF
per 1 mm Hg of PEco2. We cannot see
how these two reports are helpful in
clearing up the issue. There is a con¬
sensus that C02 is the single most
powerful determinant of CBF. There¬
fore, it is obvious that in a study where
CBF is used as an index of brain func¬
tion, control of the fluctuations of
PEco2 levels is of paramount signifi¬
cance, especially in the absence of a
valid correction factor. Stable respira¬
tion is a fundamental requirement of
the inhalation technique since the iso¬
tope recirculation correction and cal¬
culation of the start-fit time are based
Downloaded From: http://archpsyc.jamanetwork.com/ by a University of Manitoba User on 06/13/2015
end-tidal xenon concentrations. A 6.
metronome makes the task of stabiliz¬
ing respiration much easier. We have
not noticed any differences between
patients and controls in this regard.
We do not think that the differences in
C02 level between the two groups is
significant. Any standard textbook of
physiology will provide the informa¬
tion that respiratory rate is not the
sole determinant of resting C02 levels
and that even normal subjects show
wide variations. End-tidal C02 levels
can be altered substantially by chang¬
ing the depth of respiration at the same
respiratory rate.3
Unequal variances of the CBF
values between patients and controls
merit some discussion. The question of
the need to correct for this is related to
the robustness of the t test with re¬
spect to types I and II errors. There is
evidence to indicate that the t test is
robust with respect to nonnormality
and heterogeneity of variance.45 We
recalculated the t tests (two-tailed)
more conservatively, after corrections
were made for the inequalities in vari¬
ance.6 The patients continued to
show reduced CBF to several regions
(P<.05 in the right hemisphere for the
superofrontal, frontal, superotem-
poral, and prefrontal areas, and in the
left hemisphere for the frontal, supero-
temporal, and temporoparietal areas;
P<.08 in the right hemisphere for
mean CBF and the parietal and tem¬
poral areas, and in the left hemisphere
for mean CBF and the parietal area).
Large variances in unselected CBF
data are a difficulty with which most
researchers are familiar. The reasons
for this are unclear. The problem is
compounded by the heterogeneity of
schizophrenia and lack of knowledge
regarding the nature of, and interac¬
tions between, the nonspecific factors
that determine resting CBF in normal
and abnormal populations.
Roy J. Mathew, MD
re¬ Department of Psychiatry
Vanderbilt University
School of Medicine
TN 37232
Nashville,
1. Prohovnik I: Mapping Brainwork. Lund,
Sweden, Gleelrup, 1980.
2. Deshmukh VD, Meyer JS: Non-invasive
Measurement of Regional Cerebral Blood Flow
in Man. New York, SP Medical and Scientific
Books, 1978.
3. Yamaguchi F, Meyer JS, Sakai F, et al:
Normal human aging and cerebral vasoconstric-
tive responses to hypocapnia. J Neurol Sci 1979;
44:87-94.
4. Box GEP: Non-normality and tests on vari-
ances. Biometrica 1953;40:318-335.
5. Donaldson TS: Robustness of the F test to
errors of both kinds and the correlation between
the numerator and denominator of the F ratios. J
Am Stat Assoc 1968;63:660-676.
chological Research, ed 4. New York, Holt Rein-
hart & Winston, 1972, pp 97-102.
The Mini-Mental State Examination
To the Editor.\p=m-\Inresponse (Ar-
chives 1982;39:1443-1445) to a letter
by Ganguli and Saul (Archives
1982;39:1442-1443), Robins and Helzer
noted that the Mini-Mental State Ex-
amination,1 incorporated into the Di-
agnostic Interview Schedule (DIS) to
assess cognitive impairment, had been
reported by Folstein et al to differenti-
ate between pseudodementia and true
organic brain syndromes. We would
like to make that statement more spe-
cific.
The Mini-Mental State Examination
was designed as a clinical method for
grading cognitive impairment. It pro-
duces a score that can be used to follow
the course of patients or as a case
detection technique after cutoff scores
are established.
In a clinical psychiatric setting, a
low Mini-Mental score can be associ-
ated with many disorders including
mental retardation, delirium, manic-
depressive disorder, and schizophre-
nia, as illustrated by Folstein et al in
their pre-DSM-III article in 1975.1,2
However, on a medical unit like the one
from which Ganguli and Saul were
selecting patients, it has adequate spe-
cificity and sensitivity for surveys of
dementia and delirium.3
We await the results of the validation
studies being carried out at Johns
Hopkins University (Baltimore) and
Washington University (St Louis) as
part of the Epidemiological Catchment
Area Project to learn of its specificity
and sensitivity when used by lay inter-
viewers in the community. Until we
analyze these data, we are reluctant to
make claims for what it can do in that
setting.
Marshal F. Folstein, MD
Lee N. Robins, PhD
John E. Helzer, MD
Division of General Hospital Psychiatry
Osier 320
The Johns Hopkins Hospital
Baltimore, MD 21205
1. Folstein MF, Folstein SE, McHugh PR:
Mini-Mental State: A practical method for grad-
ing the cognitive state of patients for the clini-
cian. J Psychiatr Res 1975;12:189-198.
2. Folstein MF, McHugh PR: Dementia syn-
dromes of depression, in Katzman R, Terry RD,
Bick KL (eds): Alzheimer's Disease: Senile De-
mentia and Related Disorders. New York, Raven
Press, 1978, vol 7, pp 87-96.
3. Anthony JC, LeResche L, Niaz U, et al:
Limits of the 'Mini-Mental State' as a screening
test for dementia and delirium among hospital
patients. Psychol Med 1982;12:397-408.