Abnormalities of Energy Metabolism in Alzheimer's Disease Studied with PETa

Abstract

Positron emission tomography (PET) is currently the only technology affording three-dimensional measurement of the brain's energy metabolism which is closely coupled to brain function. Studies of glucose metabolism by PET of (18F)-2-fluoro-2-deoxy-D-glucose are therefore widely applied to show the contribution of various brain structures in the performance of a variety of tasks or their participation in functional deficits associated with various diseases. Although glucose metabolism decreases slightly with age to a regionally different degree, most types of dementia show severe changes in glucose metabolism. Alzheimer's disease (AD) is characterized by metabolic disturbances most prominent in the parietotemporal association cortex and later in the frontal lobe, whereas primary cortical areas, basal ganglia, thalamus, brainstem, and cerebellum are not affected. It is this typical pattern that distinguishes AD from other dementia syndromes. A ratio calculated from the metabolic rates of glucose of "affected" and "nonaffected" brain regions was able to separate patients with AD from age-matched controls and permitted the discrimination of patients with cognitive impairment of other origin in 85%. The discriminative power can be further improved by activation studies. A continuous visual recognition task increased the metabolic rate in normal subjects by 21% and in patients with AD by 6% on average, with significant regional differences. During activation the significant relation between severity of disease and temporoparietal metabolic rate became even stronger. In the assessment of effects of treatment on disturbed metabolism, PET studies demonstrated an equalization of metabolic heterogeneities in patients responding to a muscarinergic cholinagonist, whereas general increases in glucose utilization were observed with piracetam, pyritinol, and phosphatidyl-serine. The therapeutic relevance of such metabolic effects, however, must be proved in controlled clinical trials.

Relationship between Blood Flow Kinetics and Severity of Alzheimer’s Disease: Assessment of Severity Using a Questionnaire-Type Examination, Alzheimer’s Disease Assessment Scale, Cognitive Sub-Scale (ADAS_cog)

“…However, no significant differences were noted between group 5 and any of the other groups. This may support the previous consensus [34,35] that the primary sensory, motor and visual cortices, occipital region, basal ganglia, cerebellum, thalamus and brainstem are largely spared the ravages of AD.…”

Greater Metabolic Rate Decreases in Hippocampal Formation and Proisocortex than in Neocortex in Alzheimer’s Disease

“…Single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies have revealed decreases in blood flow and glucose metabolism that are relatively greater in temporal and parietal than in frontal lobes, and that tend not to extend to primary sensory areas . Ratios between metabolic rates in major brain areas discriminated better between AD patients and controls than did the metabolic rate in a single area [23,[35][36][37][38].…”

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“…Piracetam activates brain adenylate kinase and produces a significant increase in the cerebral glucose utilisation in the whole brain of rats 21 Also in man, an increase in glucose utilisation was observed 22 . Piracetam has also been observed to increase the blood flow in some situations, probably because of decreased platelet aggregation, enhancement of red blood cell deformability and reduction in adherence of damaged erythrocytes to endothelial cells 23 .…”