Glucose metabolic rate and progression of illness in Alzheimer's disease

Abstract

Thirty‐eight patients with mild to moderate Alzheimer's disease (AD) underwent a neuropsychological test battery and 18‐fluoro‐2‐deoxyglucose (FDG) positron emission tomography (PET) before beginning and at the end of a randomized double‐blind study of an experimental treatment. Twelve of the patients took placebo. In the placebo patients, Mini‐Mental State (MMS) score decreased and cortical metabolism increased significantly over the 6‐month course of the study. Correlations of metabolism with neuropsychological performance were stable over time in the placebo group. Cortical metabolism correlated significantly with performance on the Blessed Information Subtest and the MMS and showed trend correlations with performance on the WAIS Digit Symbol and Word Fluency. Patients with high relative occipital metabolism tended to do poorly on word fluency. Low baseline relative metabolism in right frontal cortex and high baseline relative metabolism in left parietal and temporal cortices and in right occipital cortex predicted more 6‐month deterioration on the World Fluency Test, suggesting that frontal metabolic deficits may precede neuropsychological deficits. Correlations of 6‐month change in MMS, Blessed and Digit Symbol performance with initial glucose metabolism were not significant.

Pathogenesis of Decreased Glucose Turnover and Oxidative Phosphorylation in Ischemic and Trauma‐Induced Dementia of the Alzheimer Type

“…The subsequent decreased ATP production 27,42 could be shown with 31 P magnetic resonance spectroscopy investigations 52 . Both techniques allow a follow‐up of the progression of the decrease of glucose turnover in patients at risk of developing Alzheimer's disease 58,64 …”

Patterns of cortical activity and memory performance in Alzheimer’s disease

“…Using positron emission tomography (PET) with 18 F-2-deoxyglucose (FDG) as a tracer, Haxby et al (1988) found parietal hypometabolism to correlate with prominent impairment in verbal comprehension, calculation, and visuospatial tasks, whereas frontal hypometabolism was correlated with more impaired verbal fluency and attention. An association between frontal cortical changes and impaired performance in verbal fluency tasks was also reported by Mann et al (1992) and Siegel et al (1995). Although these studies underline the importance of frontal, parietal, and temporal changes in AD, the question of how these heterogeneous cerebral changes contribute to memory impairment remains unresolved.…”

“…Although memory problems are often subtle in the earliest stages of AD, their steady progression may leave the patient in an almost entirely amnestic condition. Recent neuroimaging studies have demonstrated structural (Jobst et al 1992;Pantel et al 1997), spectroscopic (Lazeyras et al 1998), and functional (Mann et al 1992;Pearlson et al 1992;Siegel et al 1995; for reviews, see Santens and Petit 1997;Small and Leiter 1998) cerebral changes in AD. These changes strike primarily the temporal and parietal association cortices but generally extend to the frontal cortex with progression of the disease (Buchsbaum et al 1991;Haxby et al 1988;Mann et al 1992;Mielke et al 1994;Smith et al 1992;Stein et al 1998), especially with secondary depression (Hirono et al 1998a).…”

Preclinical Pharmacology of TAK‐147, a Novel Acetylcholinesterase Inhibitor, as a Potential Therapeutic Drug for Alzheimer's Disease

“…A considerable body of evidence suggests that a defect in energy metabolism may occur in AD (7,34,47). Positron emission topographic studies of cerebral glucose metabolism have shown that a decrease in the parietal and temporal cortices occurs early in the course of AD and may precede cognitive deficits (21, 34,72). Moreover, the reduction in cerebral glucose metabolism has been shown to correlate significantly with severity of dementia (19.48.76).…”