Normal Aging and Alzheimer's Disease - SAGE Journals

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Alzheimer's Disease. A. Klinger, *M. J. de Leon, t A. E. George, tJ. D. Miller, and :j:A. P. Wolf. New York University School of Medicine, New York; *Departments of ...

Journal of Cerebral Blood Flow and Metabolism 8:433-435 © 1988 Raven Press, Ltd., New York

Elevated Cerebellar Glucose Metabolism in Microvascular White Matter Disease: Normal Aging and Alzheimer's Disease

A. Klinger, *M. J. de Leon, tA. E. George, tJ. D. Miller, and :j:A. P. Wolf New York University School of Medicine, New York; *Departments of Psychiatry and tRadiology, New York University Medical Center, New York; tDepartment of Chemistry, Brookhaven National Laboratory, Upton, New York, U.S.A.

Summary: Young normal, elderly, and clinically diag­ nosed Alzheimer disease subjects who had undergone positron emission tomography (PET) and computed to­ mography (CT) examinations were studied to determine the effect of periventricular white matter lesions on cere­ bellar glucose metabolic rates. PET-determined cere­ bellar metabolic rates were elevated in subjects with

periventricular white matter lesions. These results sug­ gest the cautious use of cortical-to-cerebellar ratios in fu­ ture PET or single-photon-emission CT (SPECT) studies. Key Words: Positron emission tomography-Alzheimer's disease-Cerebellum-White matter disease-Periven­ tricular white matter lesions.

Positron emission tomography (PET) studies of

periventricular white matter lesions (de Leon et al.,

subjects with Alzheimer's disease have shown de­

1987). This may be further evidence of the ability of

creases in cortical metabolic rates, which are most

periventricular white matter lesions to contribute to

prominent in the temporal and parietal lobes (Chase

dementia (Hachinski et al., 1987). Postmortem

et al., 1983; de Leon et al., 1983; Friedland et al.,

studies reveal white matter rarefaction and demye­

1985). With this information, several nonquantita­ tive PET (McGeer et al., 1986) and single-photon­

rating arterioles (Brun and Englund, 1986; George

emission computed tomography (SPECT) (Holman,

et al., 1986). These microvascular changes are not

lination associated with hyalinosis of deep perfo­

1986; Mueller et al., 1986) studies have demon­

inconsistent with the final diagnosis of Alzheimer's

strated that the temporal-to-cerebellar ratio is of

disease. We now report that periventricular white

diagnostic use. We recently reported that CT peri­

matter lesions are associated with elevated cere­

ventricular white matter lesions were found in ap­

bellar metabolic rates; these results suggest the

proximately 30% of 151 Alzheimer's disease pa­

cautious use of cortical-to-cerebellar ratios in PET

tients and were associated with gait dysfunctions

or SPECT studies.

(George et al., 1986). These lesions have also been found to be associated with subtle motor findings in


Alzheimer's disease (Rezek et al., 1987). In Alz­

The diagnosis of Alzheimer's disease was made by in­ clusion and exclusion using established criteria (McKhann et al., 1984). In addition, we excluded sub­ jects on medications and those with hypertension, signifi­ cant cardiovascular disease, or metabolic disorders. Noncontrast GE 8800 CT scans were blindly evaluated for periventricular white matter lesions by two observers. There was 100% agreement between observers for the presence or absence of periventricular white matter le­ sions. In all cases, the periventricular white matter le­ sions involved the frontal white matter. In other periven­ tricular regions, the distribution of lesions was variable.

heimer's disease, using PET, patients with periven­ tricular white matter lesions show milder reduc­ tions in glucose metabolism in the temporal and pa­ rietal lobes than equally impaired patients without

Received October 23, 1987; accepted December 14, 1987. Address correspondence and reprint requests to Dr. M. de Leon, Neuroimaging Research, Millhauser Laboratories, Rm. HN-314, NYU Medical Center, 550 First Avenue, New York, NY 10016, U.S.A.




The Global Deterioration Scale was used to stage decline in cognitive functioning (Reisberg et aI., 1982). These evaluations resulted in five groups of right-handed sub­ jects: 38 young normals, 12 elderly normals without peri­ ventricular white matter lesions, 9 elderly normals with periventricular white matter lesions, and 34 mild to se­ vere Alzheimer's disease patients both without (2 1) and with ( 13) periventricular white matter lesions. The young normals ranged between 20 and 40 years, and the elderly subjects ranged between 60 and 80 years of age. The four elderly groups did not differ in age, and the two Alz­ heimer's disease groups did not differ in Global Deterio­ ration Scale scores. PET VI studies were done using llC-2-deoxy-n-glucose ( 1 1-CDG) as a tracer for glucose metabolism. Glucose metabolic rates were calculated using the Sokoloff model equation with rate contants and the measured lumped constant for ll-CDG as determined by Reivich et al. ( 1985). During the uptake period, subjects rested quietly under dim lighting with their eyes open and ears unplugged. All PET images were obtained parallel to the canthomeatal plane and attenuation-corrected using 68Ge/68Ga-de­ rived transmission scans. For each study, two sets of seven contiguous scans were obtained. The midpoints of the two scan sets were offset by 7 mm, yielding 14 over­ lapping slices, each 14-mm thick. This procedure yielded four to six slices that included the cerebellum. The slice selected was typically a middle slice demonstrating a maximal view of the cerebellum as demarcated by the bony anatomy of the posterior fossa. All PET samples were determined blind to diagnosis. Standardized cere­ bellar regions of interest were CT-defined using a dedi­ cated-image-analysis system. Three separate measure­ ments were made. Two were made in the left and right hemispheres of the cerebellum and measured 2 x 2 cm. The third measurement was made on the midline of the cerebellum and measured 1 cm wide by 1.5 cm long (ante­ rior-posterior). The cerebellar metabolic value we used in the analyses was the average of the three samples.

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GROUPS FIG. 1. Relationship between cerebellar glucose metabolic rates (in micromoles per 100 g per minute) and clinical diag­ nosis. Groups are young normals (YN, N 38); elderly normals without periventricular white matter lesions (NL, N 12); elderly normals with periventricular white matter le­ =


sions (NL+ PWML, N 9); Alzheimer's disease patients without periventricular white matter lesions (AD, N 21); and Alzheimer's disease patients with periventricular white =


matter lesions (AD + PWML, N 13). Bars represent ± 1 SEM; ·significantly different from YN, NL, and AD (p < 0.05). =

Further examination of the pattern of cerebellar metabolism revealed no group differences for either the absolute magnitude of asymmetry or the direc­ tional preference of glucose utilization (p > 0.05). DISCUSSION These data identify, for the first time, elevated cerebellar metabolic rates associated with lesions in the periventricular white matter. The pattern of sig­ nificant elevated metabolic rates was specific to the cerebellum. In our recent studies (manuscript in preparation), we did not find any evidence for ele­ vated cortical metabolic rates above the normal levels. Only in Alzheimer's disease patients with


periventricular white matter lesions was there any

A 2 x 2 analysis of variance (clinical diagnosis

evidence of relative preservation of metabolic rates

by CT diagnosis) for the four elderly groups indi­

(i.e., less reduction) in the temporal lobe as com­

cated that subjects with periventricular white

pared with pure Alzheimer's disease. Contrary to

matter lesions had significantly higher cerebellar

the observed cerebellar reductions associated with

metabolic rates than subjects without periventri­

supratentorial lesions involving both gray and white

cular white matter lesions (F[ 1,5 1]

matter (Kushner et ai., 1984; Pantano et ai., 1986),


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