Effects of Aging on Cerebral Circulation and Metabolism in Man.

Dastur, Darab K.; Lane, Mark H.; Hansen, Douglas B.; Kety, Seymour S.; Butler, Robert N.; Perlin, Seymour; Sokoloff, Louis

doi:10.1037/10776-006

Cited by 100 publications

(59 citation statements)

References 16 publications

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“…Al though it is not shown in the tables included here, all arteriosclerotic subjects also evidenced signifi cantly reduced internal jugular venous POz (JVP02), with an average of 33 mm Hg, compared with a mean of 35.9 mm Hg in the normal aged. This has been shown in the earlier detailed report by Dastur et al (1963). Our colleagues in psychiatry taking part in this multidisciplinary study detected mild manifestations of mental decline in 11 of the 48 community-resident, aged males, and found this to relate to the occurrence of arteriosclerosis and to reduced CBF and CMR02, but not solely to chro nological aging (Butler et aI.…”

Section: Pathological Agingsupporting

confidence: 70%

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Cerebral Blood Flow and Metabolism in Normal Human Aging, Pathological Aging, and Senile Dementia

Dastur

1985

J Cereb Blood Flow Metab

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123

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Summary: A review and a reappraisal are presented of earlier data on cerebral circulatory and metabolic studies in normal active elderly men (Group I) of mean age 71 years, compared with normal young subjects of mean age 21 years, conducted at the National Institutes of Health, Bethesda, MD, U.S.A., during [1956][1957][1958]. There was no significant difference in the mean CBF and cerebral met abolic rate for oxygen (CMR02) values between the two populations; i.e., these important parameters did not fall with chronological aging per se. There was significant depression in the mean cerebral metabolic rate for glu cose (CMRG) value (by -23%) in the aged compared with the young. Newer methods using positron emission to mography and appropriate isotopes have confirmed these findings in normal aging in human subjects and experi mental animals. As expected, MABP and cerebral vas cular resistance (CVR) were significantly elevated in the normal aged. MABP was even more elevated in elderly hypertensive subjects, and the CVR more elevated in the subjects with arteriosclerosis (Group II), who alsoThe World Health Organization designated 1982 as "the year of the aged," in view of the global increase of the elderly population. Whereas the av erage life expectancy in India is now � 54 years, the

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Section: Pathological Agingsupporting

confidence: 70%

“…An attempt is made to report and discuss the prin ciples and the results of studies carried out by Dastur et al (1963) at the Laboratory of Clinical Research, National Institute of Mental Health (NIMH) in Bethesda, MD, U.S.A., more than 20 years ago. This was part of a multidisciplinary study on human aging (Birren et al, 1963).…”

mentioning

confidence: 99%

Cerebral Blood Flow and Metabolism in Normal Human Aging, Pathological Aging, and Senile Dementia

Dastur

1985

J Cereb Blood Flow Metab

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123

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“…This could also have been modeled as a first-order process since glucose was maintained close to its basal level. The value assigned to this loss is based on age-interpolated data for similar subjects in the literature (35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

Insulin Control of Glucose Metabolism in Man

Insel¹,

Liljenquist²,

Tobin³

et al. 1975

J. Clin. Invest.

231

107

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A B S T R A C T Analyses of the control of glucose metabolism by insulin have been hampered by changes in blood glucose concentration induced by insulin administration with resultant activation of hypoglycemic counterregulatory mechanisms. To eliminate such mechanisms, we have employed the glucose clamp technique which allows maintenance of fasting blood glucose concentration during and after the administration of insulin. Analyses of six studies performed in young healthy men in the postabsorptive state utilizing the concurrent administration of [1'C] During the glucose clamp experiments plasma insulin levels reached a plateau of 95±8 /U/ml. Over the entire range of insulin levels studied, glucose losses were best correlated with levels of insulin in a slowly equilibrating insulin compartment of a three-compartment insulin model. A proportional control by this compartment on glucose utilization was adequate to satisfy the observed data. Insulin also rapidly decreased the endogenous glucose production to 33% of its basal level (0.58 mg/ kg per min), this suppression being maintained for at least 40 min after exogenous insulin infusion was terminated and after plasma insulin concentrations had returned to basal levels.The change in glucose utilization per unit change in insulin in the slowly equilibrating insulin compartment is proposed as a new measure for insulin sensitivity. This defines insulin effects more precisely than previously used measures, such as plasma glucose/plasma insulin concentration ratios.Glucose clamp studies and the modeling of the coupled kinetics of glucose and insulin offers a new and potentially valuable tool to the study of altered states of carbohydrate metabolism.

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“…When the Kety-Schmidt method was applied to carefully selected, elderly subjects in a clearly supe rior state of health, no age-dependent decline was found in mean CBF or mean CMR02 (Dastur et aI., 1963;Sokoloff, 1978). In more average elderly sub jects, some reduction has been found in mean CBF and mean CMR02, which is exaggerated by cerebral disease (e.g., Lassen, 1959;Dastur et a!., 1963;Ob rist, 1978;Sokoloff, 1978;Gottstein and Held, 1979;Naritomi et aI., 1979;Frackowiak et aI., 1980;Melamed et aI., 1980;Lammertsma et aI., 1981). It has been noted that the decline in mean CMRg\u is more marked than the decline in mean CBF or mean CMR02 (Dastur et aI., 1963;Gottstein et aI., 197 1;Gottstein and Held, 1979).…”

Section: Figmentioning

confidence: 99%

Effects of Human Aging on Patterns of Local Cerebral Glucose Utilization Determined by the [¹⁸F] Fluorodeoxyglucose Method

et al. 1982

J Cereb Blood Flow Metab

318

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Summary:The [IHF]fluorodeoxyglucose (FDG) scan method with positron emission computed tomography was used to determine patterns of local cere bral glucose utilization (LCMRg1u) in 40 normal volunteer subjects aged 18 to 78 years. Throughout all the studies. each subject was quiet, without movement, with eyes open and ears unplugged, exposed only to ambient room light and sound. For the entire group, whole brain mean CMRglu was 26.1 ± 6. I /Lmol 100 g-l min-1 (mean ± SD, n = 40). At age 78, mean CMRglu was, on the average, 26% less than at age 18, an alteration of the same order as the variance among subjects at any age. The gradual decline of mean CMRglu with advancing age occurred at a faster rate than was reported for mean cerebral oxygen utilization, possibly due to increasingly altered pathways for glucose utilization, or to increasing oxidation of ketone bodies or other alternative substrates. Glucose utilization in the hemispheres was symmetrical and mean CMRglU of overall cortex, caudate, and thalamus was equal in individuals at all ages. The slopes of decline with age were similar when LCM Rglu was averaged over zones corresponding to centrum semiovale, caudate, putamen, and fron tal, temporal, parietal, occipital, and primary visual cortex. However, the met abolic ratio of superior frontal cortex to superior parietal cortex declined with age, possibly due to selective degeneration of superior frontal cortex or to differences between age groups in the sensory and cognitive response to the study. These results should be useful in distinguishing age from disease effects when the FDG scan method is used. 163 koloff et aI., 1977) used in animals, but emission computed tomography is substituted for the au toradiography. After intravenous injection, FDG enters the brain, is phosphorylated by brain hexokinase, and the metabolic product, FDG-6-P0 4 , remains fixed with only slow dephosphoryla tion. The time course of specific activity is mea sured in plasma, brain activity is determined by scanning, and with knowledge of predetermined rate constants, an operational equation allows cal culations of LCMRglu that are distributed in a cross-

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Effects of Aging on Cerebral Circulation and Metabolism in Man.

Cited by 100 publications

References 16 publications

Cerebral Blood Flow and Metabolism in Normal Human Aging, Pathological Aging, and Senile Dementia

Cerebral Blood Flow and Metabolism in Normal Human Aging, Pathological Aging, and Senile Dementia

Insulin Control of Glucose Metabolism in Man

Effects of Human Aging on Patterns of Local Cerebral Glucose Utilization Determined by the [¹⁸F] Fluorodeoxyglucose Method

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Effects of Aging on Cerebral Circulation and Metabolism in Man.

Cited by 100 publications

References 16 publications

Cerebral Blood Flow and Metabolism in Normal Human Aging, Pathological Aging, and Senile Dementia

Cerebral Blood Flow and Metabolism in Normal Human Aging, Pathological Aging, and Senile Dementia

Insulin Control of Glucose Metabolism in Man

Effects of Human Aging on Patterns of Local Cerebral Glucose Utilization Determined by the [18F] Fluorodeoxyglucose Method

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Effects of Human Aging on Patterns of Local Cerebral Glucose Utilization Determined by the [¹⁸F] Fluorodeoxyglucose Method