Diminished glucose transport in Alzheimer's disease: dynamic PET studies.

Dynamic positron emission tomography with [18F]fluorodeoxyglucose was used in six patients with Alzheimer's disease (AD) and seven healthy age-matched control subjects to estimate the kinetic parameters K1*, k2*, and k3* that describe glucose transport and phosphorylation. A high-resolution tomograph was used to acquire brain uptake data in one tomographic plane, and a radial artery catheter connected to a plastic scintillator was used to acquire arterial input data. A nonlinear iterative least-squares fitting procedure that included terms for the vascular fraction and time delay to the peripheral sampling site was used to fit a three-compartment model to the brain data. Regions studied included frontal, temporal, occipital, and the entire cortex and subcortical white matter. The values obtained for the individual rate constants and regional CMRglc (rCMRglc; calculated using regional values of the rate constants) were higher than those reported previously. A significant (p less than 0.05) decrease was found in K1* in frontal and temporal cortex in the AD patients compared with the controls, with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex, respectively, of controls and 0.127 and 0.126 ml/g/min in frontal and temporal cortex of the AD patients. rCMRglc was also significantly (p less than 0.02) lower in the AD patients than controls in all cortical brain regions. Lower values of k3* were found in all brain regions in the AD patients, although these were not statistically significant. These findings provide evidence of an in vivo abnormality of forward glucose transport in AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer's disease. Age at onset and single-photon emission computed tomographic patterns of regional cerebral blood flow.

We performed this study to determine whether early- and late-onset Alzheimer's disease differ physiologically. Ten patients with a presenile (before 65 years old) onset of the disease and 16 with senile onset of the disease were evaluated clinically and neuropsychologically and studied with single photon emission computed tomography using the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine. Although the presenile subjects had more severe neuropsychological abnormalities in all realms of cognitive function, including language, and showed greater reductions in regional blood flow than the older patients, they were also more severely demented, thus complicating interpretation of the results. Two indexes of cerebral perfusion, a ratio of regional flow compared with occipital flow and a left-right asymmetry index, demonstrated relative left frontal hypoperfusion in presenile- but not senile-onset patients and did not appear to be an artifact of the severity differences. Although no asymmetry of cognitive function was noted, the perfusion asymmetry provides biological evidence for an alteration in left-hemisphere function in patients with the early onset of Alzheimer's disease.

Mental status as a predictor of daily function in progressive dementia.

To evaluate a standardized mental status exam's ability to predict activities of daily living (ADLs), Mini Mental Status Exam (MMSE) scores and ADL scores were obtained from 59 patients with progressive dementias of widely varying severity but with no other psychiatric disorders or major medical problems. The MMSE scores explained only about one-third of the variance in both instrumental ADLs and physical ADLs in the whole sample, and the MMSE and ADLs were independent of one another in the less demented half of the sample. This suggests that cognitive losses and functional impairments are two distinct aspects of dementia severity, which must be assessed separately.

Memory and regional cerebral blood flow in mildly symptomatic Alzheimer's disease.

We performed SPECT perfusion imaging and memory testing with mildly and moderately demented Alzheimer's disease (AD) patients and with healthy controls. All patients had memory abnormalities, but 5 of the 21 patients had neither temporal nor parietal perfusion abnormalities, indicating that temporoparietal blood flow may be normal at a point when memory is pathologic and the clinical diagnosis of AD is possible.

Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia.

Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer [123I]-N-isopropyl-p-iodoamphetamine. Five of these patients were clinically and psychologically different from the others, demonstrating predominant behavioral disturbances with relative preservation of memory function. These five patients, who were felt to have a frontal lobe dementia (FLD), showed SPECT perfusion patterns which differed from the remaining 25 patients, who were diagnosed as having Alzheimer's disease (AD), and from 16 healthy control subjects. The FLD patients showed diminished perfusion in orbitofrontal, dorsolateral frontal, and temporal cortex relative to controls, while the AD patients showed lower perfusion in temporal and parietal cortex than controls. The FLD patients also showed hypoperfusion in both frontal cortical regions relative to AD patients. The pattern of performance on neuropsychological testing paralleled these differences in regional perfusion. These results suggest that clinical evaluation and physiological imaging may enable the differentiation of groups of degenerative dementia patients during life.

Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease.

Nuclear magnetic resonance (NMR) imaging was employed to study 10 patients with Alzheimer's disease (AD) and seven healthy elderly control subjects. Coronal sections were used to make volumetric measurements of the hippocampus, ventricles, subarachnoid space, and brain parenchyma. The hippocampal volume (normalized relative to the size of the lenticular nucleus) was reduced by 40% in the AD group compared to the controls, with no overlap between the two groups. Overall measures of brain atrophy and ventricular and sulcal enlargement also showed significantly different group means, although with overlap between the two groups. Hippocampal atrophy did not correlate with either overall brain atrophy or dementia severity, although the degree of brain atrophy was correlated with dementia severity. These results show that NMR is capable of providing in vivo quantification of diminished hippocampal size in AD which is not correlated with overall brain atrophy and which may differentiate AD from normal aging.