Mony J. de Leon, Steven H. Ferris, * Ajax E. George, Barry Reisberg,. tDavid R. ... (de Leon et aI., 1980; Jacoby and Levy, 1980; Gado .... Collins DWK, Mastaglia.
Journal of Cerebral Blood Flow and Metabolism
3:391-394 © 1983 Raven Press, New York
Short Communication
Computed Tomography and Positron Emission Transaxial Tomography Evaluations of Normal Aging and Alzheimer's Disease
Mony J. de Leon, Steven H. Ferris, * Ajax E. George, Barry Reisberg, tDavid R. Christman, *Irvin I. Kricheff, and tAlfred P. Wolf Departments of Psychiatry and *Radiology, New York University Medical Center, New York, and tDepartment of Chemistry, Brookhaven National Laboratory, Upton, New York, U,S.A,
changes. Although both structural and biochemical changes occur in SDAT, the biochemical changes are more marked. The results suggest that PETT is potentially more useful than CT in the in vivo diagnosis of SDAT. Key Words: Computed tomography-Global Deterioration Scale-Hemispheric glucose metabolic rate-Pearson product-moment correlations-Positron emission trans axial tomography-Senile dementia of the Alzheimer's type.
Summary: Young normal subjects, old normal subjects, and patients with senile dementia of the Alzheimer's type (SDAT) were studied with both computed tomography (CT) and positron emission transaxial tomography (PETT). Increases in ventricular size with both aging and disease were measured. Regional glucose metabolic rate was not affected by age, but was markedly reduced in SDAT pa tients. These data indicate that in normal aging, structural brain changes may be more salient than biochemical
1970; Simard et aI. , 1971; Hagberg and 1976; Yamaguchi et aI. , 1980), as have the
Obrist et aI. ,
Recent computed tomography (C T) studies of brain structure in vivo in normal human aging have
Ingvar,
consistently indicated age-related changes (Barron
studies
et aI. ,
axial tomography (PETT) technique (Ferris et aI. ,
1976;
Glydensted and Kosteljanetz,
1976;
1976; Jacoby et aI. , 1980; Yama· 1980; Cala et aI. , 1981; Hughes and 1981; Zatz et aI. , 1982). However, recent re
with
the
positron
trans
Hahn and Rim,
1980;
mura et aI. ,
Ferris et al.,
Gado,
inconsistent results. In a recent summary of non
Frackowiak et aI. ,
1983).
1981;
emission
de Leon et aI. ,
1983;
But studies of normal aging show
(1983)
views cite the results for senile dementia of the A lz
tomographic studies, Davis et aI.
heimer's type (SDAT ) as having been inconsistent
that at least eight studies indicated no age-related
(de Leon et aI.,
changes in oxygen metabolism, whereas four studies
et aI. ,
1982;
1980;
1980; Gado 1983). On the
Jacoby and Levy,
George and de Leon,
reported
report diminutions. The results from PETT studies
other hand, nontomographic in vivo studies of brain
are also unclear. In related studies, Lammertsma et
function (i. e . , cerebral blood flow and metabolism)
aI.
have indicated consistent disease-related diminu
trend of diminishing gray matter oxygen metabo
tions (Freyhan et aI. ,
lism with age only until the fIfth decade. Using PETT
1951;
Lassen et aI. ,
1960;
(1981)
and Fieschi and Lenzi
(1983)
to study glucose metabolism, Kuhl et al.
reported a
(1982) found
an age-dependent but variable decline in regional
(1983), Ferris et (1983) found no ev
metabolic rates, but de Leon et aI.
Address correspondence and reprint requests to Dr. de Leon at Millhauser Laboratory, Department of Psychiatry, NYU Med ical Center, 550 First Avenue, New York, New York 10016, U.S.A. Abbreviations used: CM, Canthomeatal; CT, computed to mography; FDG, 18F-2-deoxy-2-fluoro-D-glucose; GDS, Global Deterioration Scale; PET T, positron emission transaxial tomog raphy; SDAT, senile dementia of the Alzheimer's type.
aI.
(1983),
and Rapoport et aI.
idence for age-related changes in glucose metabo lism. It is possible that a number of methodological variables, such as subject selection criteria and methods of scan analysis, may account for these
391
M. J. de LEON ET AL.
392
inconsistent results (Sokoloff, George,
1983).
1979;
de Leon and
With these considerations in mind,
we attempted to resolve the issue of structural versus metabolic change in aging and dementia. We now report the results of the first study, in which both structural data from CT and metabolic data from PETT were obtained on the same groups of young normal, old normal, and SDAT subjects.
SUBJECTS AND METHODS The groups consisted of 14 young normal subjects (mean age, 26.2 ± 5.3 years), 21 elderly normal subjects (mean age, 67.4 ± 6.7 years), and 23 SDAT patients (mean age, 73.1 ± 6.9 years). A ll subjects received a clinical evalu ation which included comprehensive medical, neurolog ical, psychiatric, neuropsychological and clinical labora tory assessments. Based upon the 7-point Global Dete rioration Scale (GDS) (Reisberg et aI., 1982), the global severity of the SDAT patients ranged from mild to severe (GDS = 3-6). Control subjects had GDS scores of 1 or 2. All clinical studies including CT were performed at NYU Medical Center. CT images were generated by a General Electric GE CT/T 8800 scanner, with one scanning pro tocol for all subjects. The PETT studies were conducted at the Brookhaven National Laboratory with the PETT III scanner. 18F-2-Deoxy-2-fluoro-n-glucose (FDG) was used as a physiologic tracer for glucose. The standardized PETT scanning procedure began after a 30-min tracer uptake period. In all instances, this was an adequate in terval for tracer levels in the blood to reach equilibrium. Throughout the tracer uptake period, the subjects rested with their eyes closed in a quiet, dimly lit scanning room. A ll scans were taken parallel to the canthomeatal (CM) plane at lO-mm intervals above CM (0 mm). For the CT analyses, the brain slice was selected that depicted the basal ganglia, the third ventricle, and the pineal body (which was often calcified). A PETT image at a comparable brain level was determined from the fi ducial markings on both imaging machines. From the CT X-ray film, an estimation of structural change was deter mined by the evaluation of ventricular size. The estimate of ventricular size was determined from the following linear measurements: the width of the frontal horns, the 45° width of both frontal horns, the bicaudate diameter, and the width of the third ventricle. In addition, separate
brain-width measurements were determined in a plane passing through each ventricular measurement and ex tending from inner table to inner table of the skull. A ventricle-brain ratio was then computed for each ventric ular measure. For the 45° width of the frontal horns, the width of the brain at the level of the third ventricle was used. The arithmetic sum of these ratios was calculated as the composite estimate of ventricular size. We have previously determined that this ventricular size statistic is correlated with overall ventricular volume (r = 0.75; n = 88; p < 0.(001), and has excellent interobserver re liability (r = 0.94, n = 63, p < 0.0001). For PETT, the average metabolic rate was determined for the entire slice and for the right and left hemispheres separately. Since the SDAT group was slightly but significantly (p < 0.05) older than the elderly normal group, all statistical comparisons between these two groups were controlled for age with covariance analyses and age-corrected means. Correlation analyses involving the two elderly groups em ployed a partial correlation for age.
RESULTS T he CT and PETT results for the three subject groups are presented in Table
1.
C omparisons among
the groups indicate that ventricular size increases significantly with normal aging, with a further sig nificant increase in SDAT. Specifically, there is an increase of
13%
in the elderly normal subjects rel
ative to the young normal subjects, and an increase of
11%
in the SDAT group relative to the elderly
controls. For the PETT measures, we find no sta tistically significant differences in glucose metabo lism between the young and the elderly normals. However, for the SDAT group relative to the elderly controls, there is a highly significant diminution of
�23%
in the rate of glucose metabolism.
We also examined the degree of relationship be tween the magnitude of the cognitive impairment (GDS score) in the SDAT group, and the extent of brain change as indicated by the CT and the PETT measures. T hese results indicate a significant as sociation between the measure of cognitive impair ment and the PETT measures, but not a close as-
TABLE 1. CT and PETT brain measures in young, normal elderly, and SDAT groups Young (n = 14)
Elderly (n = 21)
0.53 1 ± 0.055
0.613 (0.633) ± 1.01c
Brain measure CT ventricular sizea PET metabolic rateb Right hemisphere Left hemisphere Whole slice
3.74 ± 0.60 3.60 ± 0.56 3.67 ± 0.58
3.84 (3.82) ± 0.61 3.62 (3.59) ± 0.55 3.73 (3.71) ± 0.58
a Composite of ventricular-brain ratios. b Rate of glucose utilization (mg/min/100 g), C Young vs. normal elderly; p < 0.0 1. d Normal elderly vs. SDAT; p < 0.05 (age-adjusted). e Young normal vs. SDAT; p < 0.01. f Normal elderly vs. SDAT; p < 0.0001 (age-adjusted). Values are means ± SD. Values in parentheses are age-adjusted means.
J Cereb Blood Flow Metabol, Vol. 3. No.3, 1983
SDAT (n = 23) 0.734 (0.714) ± 0.105d,e 3.10 (3.12) ± 0.58e,[ 2.87 (2.91) ± 0.61e,[ 2.99 (3.02) ± 0.5ge,[
CT AND PETT IN AGING AND ALZHEIMER'S DISEASE
393
sociation between the GDS and ventricular size. The
E xamination of the relationship between ventric
Pearson product-moment correlations between GDS
ular size and metabolic rates suggests that for nei
and PETT were
ther normal aging nor SDAT are the structural brain
-0.51
-0.54
for the right hemisphere,
whole slice (n
=
23,
p
44;
p
