Clinical studies in Alzheimer patients with positron emission tomography.
Brain imaging techniques will in the future play an important role in the assessment of patients with neurogenerative disorders such as Alzheimer's disease (AD). An early diagnosis of AD is today hampered by lack of reliable diagnostic markers. Positron emission tomography (PET) permits the quantification and three-dimensional imaging of physiological variables. This provides the clinician with a non-invasive imaging technique which allows in vivo quantification of physiological processes in AD underlying dysfunction of cognition. PET studies regarding changes in cerebral blood flow and metabolism are rather consistent at least in moderate/advanced cases of AD. How early in the progress of the disease deficits in these parameters can be observed is still an open question. Longitudinal studies will here be important and especially in individuals with a family history of AD. Since deficits in cholinergic neurotransmission have been measured in autopsy AD brains attempts have also been made to visualized cholinergic activity in vivo. Nicotinic and muscarinic receptors have been visualized in normal and AD brains. A reduced uptake and binding of [11C]nicotine in the temporal and frontal cortices have been measured in AD patients by PET. Few treatment studies in AD have been evaluated by PET. Long-term treatment with the cholinesterase inhibitor tacrine increase the uptake of [11C]nicotine. Significant reduction in uptake between the two enantiomers (S)(-) and (R)(+)-[11C]nicotine has been observed compatible with a restoration of nicotinic receptors. Tacrine also significantly increased the glucose metabolism. PET studies indicate that long-term tacrine treatment in AD patients with mild dementia improves functional activities in brain. When an AD patient with moderate dementia was treated with nerve growth factor (NGF) PET studies revealed increase in cortical blood flow and nicotinic receptors. PET studies will in the future play an important role in the evaluation of new therapeutic drug strategies in AD.
Nordberg
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Department of Geriatric Medicine, Karolinska Institute, Huddinge University, Hospital, Sweden.
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000503:physiopathology; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D009414:Nerve Growth Factors / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000502:physiology*; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
D001786:Blood Glucose; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic