The purpose of this review is to extend the existing application of the frontal lobe hypothesis of cognitive aging beyond the limited work on inhibitory control (F. N. Dempster, 1992) to include memory processes supported by the prefrontal cortex. To establish a background for this analysis, I review existing models of prefrontal cortex function and present a synthesized model that includes a general function of temporal integration, supported by 4 specific processes: prospective memory, retrospective memory, interference control, and inhibition of prepotent responses. I found the frontal lobe hypothesis to perform well, with the exception of an inability to account for age-related declines in item recall and recognition memory, possibly a result of age-related declines in medial temporal function.

An application of prefrontal cortex function theory to cognitive aging.

D2 dopamine and S2 serotonin receptors were imaged and measured in healthy human subjects by positron emission tomography after intravenous injection of 11C-labeled 3-N-methylspiperone. Levels of receptor in the caudate nucleus, putamen, and frontal cerebral cortex declined over the age span studied (19 to 73 years). The decline in D2 receptor in males was different from that in females.

http://science.sciencemag.org/content/sci/226/4681/1393.full.pdf

Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain

The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder.

Twenty-one patients with a clinical diagnosis of dementia of the Alzheimer's type (DAT) and 29 healthy, age-matched controls were studied using positron emission tomography (PET) and [18F]2-fluoro-2-deoxy-D-glucose to measure regional cerebral glucose consumption in the resting state. Reductions in ratio measures of relative metabolism in some parietal, temporal, and frontal regions were found in mild, moderate, and severe DAT groups. A significant increase in right/left metabolic asymmetry, particularly in parietal regions, also was seen in mild and moderate groups. Only in the severely demented patients was the absolute cerebral metabolic rate reduced significantly from control values. Fourteen patients had repeated PET studies, but only those patients with moderate to severe dementia showed a decline in IQ over 6 to 15 months. There were no significant changes in metabolic measures over time. PET is useful in quantifying regional cerebral dysfunction in DAT, even in the early stages of the disease.

Positron emission tomography in Alzheimer's disease

Current neuropsychological models propose that some age-related cognitive changes are due to frontal-lobe deterioration. However, these models have not considered the possible subdivision of the frontal lobes into the dorsolateral and ventromedial regions. This study assessed the age effects on 3 tasks of executive function and working memory, tasks dependent on dorsolateral prefrontal dysfunction; and 3 tasks of emotion and social decision making, tasks dependent on ventromedial prefrontal dysfunction. Age-related differences in performance were found on all tasks dependent on dorsolateral prefrontal dysfunction. In contrast, age-related differences were not found on the majority of the tasks dependent on ventromedial prefrontal dysfunction. The results support a specific dorsolateral prefrontal theory of cognitive changes with age, rather than a global decline in frontal-lobe function.

Age, executive function and social decision making: A dorsolateral prefrontal theory of cognitive aging.

Positron emission tomography (PET) scanning with 18F-2-deoxy-D-glucose was employed to examine hemispheric and regional rates of cerebral glucose utilization in 21 resting healthy men between the ages of 21 and 83 years. The eyes of the subjects were covered and the external auditory canals were plugged with cotton in the 45 minutes following injection of tracer. Mean hemispheric cerebral metabolic rates for glucose (CMRglc) averaged 4.3 to 4.4 mg x 100 g-1 X min-1, and mean hemispheric grey matter glucose utilization, (CMRglc)grey, averaged 5.2 to 5.3 mg x 100 g-1 X min-1. Neither parameter was correlated significantly with age, nor were their right/left ratios correlated with age (P greater than 0.05). The mean ratios, furthermore, did not differ significantly from 1. Regional cerebral metabolic rates for glucose, rCMRglc, at each of 31 identified midline and bilateral structures also were not correlated significantly with age. Mean rCMRglc ranged from 2.6 mg X 100 g-1 X min-1 at the centrum semiovale to 6.2 mg . 100 g-1 X min-1 at the precentral gyrus of the frontal lobe and precuneus of the parietal lobe. The results indicate that the cerebral metabolic rate for glucose is not correlated with age in healthy men.

B. J. Koziarz

Papers

Cerebral glucose utilization, as measured with positron emission tomography in 21 resting healthy men between the ages of 21 and 83 years.