NEURORADIOLOGY

Computed Tomography and Aging of the Brain’

Charles P. Hughes, M.D. and Mohktar Gado, M.D.

Clinical assessment of patients with varying degrees of dementia disclosed no significant

neurologic disease. Computed tomography (CT) studies of these patients permitted the
measurement of ventricular and sulcal sizes which did not apparently relate to mental sta-
tus, but which did relate to age.

INDEX TERMS: Head, computed tomography, 1(0).121 1 Computed

#{149} tomography, indications Aging
#{149} Dementia
#{149}

S Brain, volume (Skull, other fundamental

#{149} observation, 1 [0].919)

Radiology 139:391-396, May 1981

HE study of cerebral atrophy with computed tomogra- precluded examinations for adequate mental status, or if
4 phy (CT) has been of interest since the introduction of they had been discharged from the hospital before clinical
this method for brain imaging in 1974. While shrinkage and interviews. Some patients were referred from the Neu-
loss of brain substance had been clinically (1) and patho- rology and Psychiatry services; most referrals came from
logically (2, 3) associated with dementia, CT was expected the Internal Medicine Department.
to aid in the identification of presenile and senile dementia. The clinical investigation consisted of a review of all
Limitations of this method included poor resolution of pertinent records, patient interviews and, where appno-
cortical sulci-particularly with earlier machines-and, pniate, interviews with collateral sources of information.
until recently, the inability to distinguish gray and white Taking all information into account, the patient was given
matter. In addition, for higher cranial sections, the usual a Clinical Dementia Rating (CDR), developed and stan-
plane of CT demonstrates the fnontopanietal convexity but dardized by members of the Dementia Study Group at
not the surfaces of the temporal lobes where prominent Washington University.
Alzheimer disease (AD) is often present. This group recognized deficiencies in existing systems
A number of studies addressed the normative data for which tried to use either numerical scoring of functional
subjects of various ages (4-10), and the effect of the abilities or psychometric tests to determine the existence
presence of dementia (1 1- 18). Some seem to agree that and degree of dementia in a patient. As a result, a global
ventricular size increases with age. This increase and age rating was devised to categorize and score six functions:
may be related to the presence of dementia, though a memory (which receives the most emphasis), orientation,
number of exceptions preclude such a conclusion. In a judgment and problem solving, involvement in community
recent letter, Fox (19) referred to his group’s experience affairs, home life and hobbies, and personal care. A patient
and emphasized that, while CT was invaluable in identifying can receive a score for each category: 0, normal function;
aged patients with potentially treatable causes of dementia, 0.5, questionable dysfunction; 1 .0, mild dysfunction; 2.0,
findings of cerebral atrophy could not be interpreted. We moderate dysfunction; 3.0, severe dysfunction. A patient
attempted to examine this hypothesis, using a relatively can receive a global rating of dementia on the same basis
unselected group of patients referred for CT. (TABLE l).2 In unpublished work at Washington University
it was found that most patients can be unambiguously
MATERIALS AND METHODS placed in one category or another and that inter-rater re-
liability is high (correlation coefficient 0.87). The Short
From October, 1 977 to May, 1 979, one of us (MG) ex- Portable Mental Status Questionnaire (21) was also ad-
amined CT scans of hospitalized patients at least 65 years ministered to a number of the patients. Formal psycho-
of age. MG excluded cases with probable cerebral in- metric tests were not used, but the use of global ratings
fanctions on mass lesions, and probable communicating
\. hydnocephalus, using criteria established here (20). The
remaining patients were referred to one of us (CPH) who AbbrevIatIons Used:
CDR clinical dementia rating
examined the patients while they were still in the hospital. vs ventricular score
Here, more patients were excluded if clinical investigation AD Alzhelmer disease
MID multiInfarct dementia
indicated significant history of cerebrovascular disease,
55 sulcal score
head trauma, alcoholism on previous intracranial surgery.
Patients were also excluded if their medical conditions

1 From the Department of Neurology and Neurological Surgery and The Edward Mallinckrodt Institute of Radiology, Washington School of Medicine,
St. Louis, Missouri. Received July 31, 1980, and accepted November 25. bc
2 Details about the use of this rating scale can be obtained on request. (See reprint address.)

391
392 CHARLES P. HUGHES AND MOHKTAR GADO May 1981

TABLE I: THE CL INICAL DEMENTIA RATING

Cognitive Questionable
Function No Dementia Dementia Mild Dementia Moderate Dementia Severe Dementia
Only (CDR 0) (CDR = 0.5) (CDR = 1.0) (CDR = 2.0) (CDR = 3.0)

Memory No loss, or slight Mild, consistent Mild to moderate Severe loss (only Severe loss (only
inconstant forgetfulness loss (hinders highly learned fragments
forgetfulness (benign everyday activities) material retained) remain)
forgetfulness)
Orientation 100% 100% Some trouble with No sense of time; May be lost in home;
time and geog- often disoriented to only orientation to
raphy; oriented place; oriented to person may remain
for person and person
usually place
Judgement and Normal; does well Only doubtful Usually maintained Marked impairment Totally incapable
problem impairment on social basis;
solving moderate
impairment
Involvement in Independent function Only doubtful or May appear normal, No independent No independent
community at usual level mild impairment but is unable to function outside function outside
affairs function home home
independently
Home life and Well maintained Maintained or More difficult Only simple No significant function
hobbies slightly impaired activities abandoned functions main- outside personal
tamed area
Personal care Capable of Capable of Capable of self-care; Needs some help Needs much help; may
self-care self-care needs prompting with dressing and be incontinent
hygiene

permitted the inclusion of a wide variety of patients, Four linear measurements of the ventricular system
ranging from the normal to the severely demented for were made (Fig. 2). Three of these measurements were
whom cognitive measures gave no meaningful results. taken from the image at the level of the fonamen of Monro:
The youngest of the 100 patients in this study were A the width of the third ventricle; B the sum of the
65-years-old. The mean age was 75.4 ± 6.9 years. The shortest distances between the caudate nucleus and
I
distribution of men and women was nearly equal, but a septum pellucidum; C = the width of the lateral ventricles
preponderance of white patients reflected the inpatient just anterior to the foramen of Monno. D the width of the
population-at Barnes Hospital (Fig. 1). All patients were narrowest part of the bodies of the lateral ventricle. The
scanned3 using an image matrix of 160 X 160 pixel ele- widest intenpanietal distance was measured from the image
ments and a section thickness of 8 mm. For this study showing that part of the ventricle. A ventricular scone (VS)
contrast material was not used. was obtained with the following equation:

A+ B+ C+ D
VS= x 100. (1)
(I,
intenpanietal distance
I-
U A sulcal scone (SS) was also obtained from the sum of
w the four largest sulci scanned in the upper three sections.
All of the measurements were made in millimeters, using
(I)
a comparator (a magnifying lens with a neticule), and po- 4
-J
-J lanoid prints. Accuracy was judged to be within 0.5 mm.
Statistical manipulations of the data were performed
LL with the Statistical Analysis System package, version
0 79.1.
F-
z
LU
U RESULTS

LU Roughly 47 % of each race and sex was mildly, mod-

erately on severely demented (Fig. 3). As reflected in the
CDR, no apparent relationship existed between measures
Race Sex
of brain mass used, and mental status. VS was plotted
Fig. 1. Bar graph, showing the distribution of against CDR (Fig. 4). Those with no dementia were grouped
patients by race and sex. B = Black, W = White, M with those for whom the diagnoses were questionable.
= Male, F = Female.
Similarly, no significant relationship existed between
measures of mental function and SS (Fig. 5). Examination
3 A 1005 EMI dedicated head scanner was used. of the data for distributions by sex yielded apparently the
Vol. 139 COMPUTED TOMOGRAPHY AND AGING OF THE BRAIN 393 Neuroradiolo9y

I-
U
LU
,-

Zcc3
LUD
U/)

U-
0

ALL BWFM
Fig. 3. Bar graph, showing the distribution of clinical de-
Fig. 2. Diagram showing cross sections at the levels of the foramen mentia by race and sex. (COR-1, 2, 3) B Black, W White,
of Monro (left), and the bodies of the lateral ventricles (right). A the F Female, M = Male.
width of the third ventricle. B the sum ofthe shortest distances be-
tween the caudate nucleus and the anterior end of the septum peilu-
cidum on both sides. C the width of the lateral ventricles just anterior
to the foramen of Monro. 0 the narrowest part of the bodies of the difference with respect to age. The VS and SS were ex-
lateral ventricles.
amined in relation to the CDR for older and younger pa-
tients (Figs. 8 and 9). Patients were grouped by age: those
65 to 74 years, and those 75 to 84. Only a few of the pa-
same results (Figs. 6 and 7), though a difference seemed tients in our series were oven 85-years-old. A consistently
apparent in the relationship of sex to VS. larger mean ventricular size was noted in members of the
A relationship between measures of brain masses and olden group in each category of mental function. A similar
mental functions could not be established. There was a finding was seen in measures of sulcal size in all but the
mildly demented patients (CDR = 1.0).
The interrelationships of VS, SS and age were also
noted in the statistical manipulations of data from the 100
patients. If the effects of sex, race and CDR were elimi-
80 nated, age greatly affected the VS (p 0.009), and
weakly-but still significantly-affected the sulcal score
(p = 0.043). If the effects of sex, race and age were
70
eliminated, there was no significant relationship between
the CDR and VS (p 0.59) or the CDR and the 55 (p
60 0.53). There was no significant correlation between the
ventricular and sulcal measures (p 0.2).
30

8-
>40

30 6

LI)

20 LI)

}
10 2

0
I I I I

0 05 2 3
2 3
05
CDR CDR
Fig. 4. Graph showing the relationship of the VS and COR. Those Fig. 5. Graph showing the relationship of 55 and CDR. Those pa-
patients with no dementia or questionable dementia (CDR 0 or 0.5, tients with no dementia or questionable dementia (CDR 0 or 0.5,
respectively) are grouped together. Each bar indicates one standard respectively) are grouped together. Each bar indicates one standard
deviation. deviation.
394 CHARLES P. HUGHES AND MOHKTAR GADO May 1981

90 8

80
4

/)
>
70

60

50
1
(I)

: }0
Men
#{163}

OWomen

2 3
A

0.5
40
CDR

Fig. 7. Graph showing the relationship of the 55 and COR for men
30
, #{163}:Men
O:Wen
and women.
=
Patients
0 or 0.5, respectively)
standard deviation.
with no dementia or questionable
are grouped together. Each
dementia
bar indicates
(COR
one

20

10

encountered in attempting to determine the number of cells

_3 in parts of the human brain. Several studies, more recent
05 than Brody’s, tend to confirm the latter’s findings (26, 27)
CDR that in the cerebral cortex the number of neurons dimin-
ishes with age; however, no definite relationship could be
Fig. 6. Graph showing the relationship of the VS and CDR for men
and women. Patients with no dementia or questionable dementia (CDR established between such cell counts and dementia, de-
= 0 or 0.5, respectively) are grouped together. Each bar respresents spite a widespread impression of neuropathologists that
one standard deviation.
a loss of neurons accompanies various dementias. Brody
(26) did find, however, that cell loss varied with age-
ranging from no apparent loss in the postcentral gyrus to I

DISCUSSION a 60% loss in the superior temporal gyrus.

Morphologic (28) and biochemical studies (29) have
When CT scans demonstrate larger ventricular space suggested that dendnitic processes atrophy with age and
and larger cerebral sulci, there is no reason to believe that dementia. In rats the extracellular space diminishes with
the apparent loss of brain substance is not real. This study age (30). This finding is difficult to extrapolate to other
shows a correlation of advancing age not only with in- species, but may suggest that this space also changes with
creasing ventricular size, but also with enlarging sulci, age.
though the latter is slightly less convincing. At the same Therefore, shrinkage of the brain with age probably
time, statistics did not disclose an interrelationship be- involves gray and white matter, at least in the cerebral
tween dementia and either ventricular on sulcal size. Fur- hemispheres. Certain studies have suggested that various
thenmore, there are excellent examples-present and past brainstem nuclei may not lose cells with age (31-34). This
(1 2)-not only of severely demented patients with normal and Bnody’s (26) findings about the cerebral cortex suggest
ventricles and sulci, but also of non-demented patients with that such atrophy may be far from uniform in various parts
abnormal ventricles and sulci. of the brain. Evidence now suggests that cell number,
Satisfying explanations for these findings are not yet dendnitic volume and extracellular space may diminish in
available. While subject to the usual criticisms of cross- gray matter. However, little is known about a similar pro-
sectional studies, however, a number of investigations on cess in white matter, though it likely diminishes with age,
patients born more than a century apart do suggest that too, because ventricular size has been reliably correlated
brain weight decreases with age-absolutely, and in with age. Therefore, cell processes must diminish in
relation to body height-particularly after age 65(22-24). relation to loss of the cell body. Since the abnormalities
Pearl (25) demonstrated that, in younger (23 to 30 years in AD are usually widespread, such a process in old age
of age) and older (80 years of age) patients, the variations probably wOuld further increase the normally occurring loss
of brain weights differed (1,000 to 1,850 g and 1,000 to of brain substance. Senile dementia seems associated with
1,450 g, respectively). He also observed that the upper and destructive processes in the brain, in contrast to certain
lower limits of brain weight (750 to 1,250 g) were smaller biochemical storage diseases which seem to add brain
in those with senile dementia. bulk in children. However, this correlation between de-
Efforts to understand what part of the brain is disap- mentia and brain atrophy has not received convincing ra-
peaning have been frustrated by the statistical problems diologic confirmation.
 Vol. 139 COMPUTED TOMOGRAPHY AND AGING OF THE BRAIN 395 Neuroradiology

90
8 - :
#{149}
: Younger
Older

80

if
i}
70
LI)
LI)

60
I :
50
(I)
‘ >
0
40 2 3
0.5
CDR
30 . : Younger Fig. 9. Graph showing the relationship of the 55 and CDR for
. :QIder younger (65 to 74-year-old) and older (75 to 84-year-old) patients. Pa-
tients with no dementia or questionable dementia (COR 0 or 0.5,
20 respectively) are grouped together. Each bar indicates one standard
deviation.
10

0 1 2 3
0.5
CDR Patients with dementia usually cannot be diagnosed
accurately in life; however, autopsies have often suggested
Fig. 8. aph showing the relationship of the VS and CDR for the pathologic diagnosis of AD (3, 35) if the following
younger (65 to 74-year-old) and older (75 to 84-year-old) patients. Pa-
tients with no dementia or questionable dementia (COR 0 or 0.5,
metabolic and neurologic conditions can be excluded:
respectively) are grouped together. Each bar indicates one standard Parkinson disease, Huntington disease, infection of the
deviation. central nervous system, brain tumor, communicating hy-
drocephalus, progressive supranuclear palsy, major ce-
nebral vascular disease, and multiple sclerosis. Of the
Gosling (1 ) used air encephalography to demonstrate patients with dementia, about 50 % will have an anatomic
apparent atrophy in 85 % of primarily younger patients with diagnosis of AD, 10% to 15% will have multi-infarct de-
dementia. His work also showed non-demented patients mentia (MID), 10% to 15% will have a mixture of AD and
with some atrophy. Huckman et a!. (1 2) performed the first MID, and the rest will have an indefinable pathologic dis-
major CT study of this subject and suggested that a con- ease, or a rare vascular, degenerative, metastatic process
relation existed between atrophy and dementia, but noted not diagnosed in life. Seven percent of these patients may
exceptions. However, further studies (14) showed no re- have idiopathic parkinsonism, though a recent study sug-
lationship between atrophy and EEG changes, and found gested that a majority of these patients with Parkinson
that these radiologic measurements did not predict mor- disease may have prominent AD at autopsy (36).
tality in demented patients (1 5), while certain psychometric While CT can demonstrate age-related atrophy of the
and EEG changes did. brain, changes peculiar to global dementias cannot be
More recently, Kaszniak et a!. (18) studied 78 older reliably predicted, presently, by a single study of one pa-
patients with dementia. When the effects of age and ed- tient. However, these changes and age have a pronounced
ucation were taken into account, the results suggested that relationship-a constant finding in studies of this kind-
cerebral atrophy identified by CT methods correlated though we found no apparent relationship between de-
somewhat with certain cognitive functions (verbal recall, mentia and CT measures. Dementia in old age may relate
sentence production), but not with others (praxis, onien- to: very subtle differences in brain mass; changes in sy-
tation, digit span, visual memory). Similar results were napses, or only in certain critical areas; primarily bio-
obtained by Earnest et a!. (1 6) in a study of 59 non-de- chemical processes; or, more likely, a combination of
mented patients over 60-years-old, though significant ef- these factors. To this end, more quantitative CT methods
fects of age were seen here, as well. In a study of 43 olden, (37, 38), serial studies of the same patients over time, or
demented patients, de Leon et a!. (1 7) used a slightly dif- possibly some application of positron emission tomogra-
ferent CT method to demonstrate some relationship be- phy may better demonstrate the significant changes related
tween ventricular and sulcal enlargement and performance to dementia in elderly patients. However, in the initial as-
on psychometric tests. Without using measurements, na- sessment of a patient with dementia, CT scanning remains
diologists ranked scans according to increasing ventricular valuable as a means to exclude cerebnovasculan disease
and sulcal sizes. Significant correlations were noted be- on single out potentially treatable lesions such as neo-
tween these rankings and cognitive data. plasms on hydrocephalus.
396 CHARLES P. HUGHES AND MOHKTAR GADO May 1981

ACKNOWLEDeMENT: The considerable help of Dr. Leonard Berg and 16. Earnest MP, Heaton RK, Wilkinson WE, et al: Cortical atrophy,
other members of the Dementia Study (‘oup of Washington University ventricular enlargement and intellectual impairment in the aged.
and of Dr. Richard Torack of the Department of Pathology is appre- Neurology 29:1 138-1 143, Aug 1979
ciated. Dr. Reimut Wette of the Division of Biostatistics assisted in the 17. de Leon MJ, Ferris SH, Blau I, et al: Correlations between
computerised tomographic changes and behavioural deficits in
statistical analysis. Patti Vessell was of considerable help in the
senile dementia. Lancet 2:859-860, 20 Oct 1979
preparation of the manuscript.
18. Kaszniak AW, Garron DC, Fox JH, et al: Cerebral atrophy, EEG
slowing age, education, and cognitive functioning in suspected
Charles P. Hughes, M.D.
dementia. Neurology 29:1273-1279, Sep 1979
Department of Neurology
19. Fox JK, Kaszniak AW, Huckman M: Computerized tomographic
Washington University School of Medicine
scanning not very helpful in dementia-nor in craniopharyngioma.
600 South Euclid Avenue
N EngI J Med 300:437, 22 Feb 1979
Box 8111
20. Gado MH, Coleman RE, Lee KS, et al: Correlation between
St. Louis, MO 63110
computerized transaxial tomography and radionuclide cistern-
ography in dementia. Neurology 26:555-560, Jun 1976
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