Cholinergic Neurotransmission Has Different Effects on Cerebral Glucose Consumption and Blood Flow in Young Normals, Aged Normals, and Alzheimer's Disease Patients

Altered Neural Cholinergic Receptor Systems in Cocaine-Addicted Subjects

“…Earlier studies suggesting that physostigmine did not significantly alter rCBF in healthy controls suffered from subthreshold doses of physostigmine (Blin et al, 1994b;Geaney et al, 1990) or relatively insensitive measures of cerebral blood flow (Gustafson et al, 1987). Although Blin et al (1997Blin et al ( , 1994a used a maintenance physostigmine and bolus scopolamine dosing strategy somewhat similar to ours, this group reported consistent decreases in regional glucose consumption after physostigmine and generalized increases with scopolamine in healthy controls. The most striking difference in methodology is our use of functionally derived ROIs compared with Blin et al's use of larger anatomically derived ROIs, allowing us substantially more rigor in isolating specific areas of neural change.…”

VEGFR1 and VEGFR2 in Alzheimer’s Disease

“…In addition, further work is needed to determine precisely why this signaling pathway does not function normally. decreased cholinergic innervation of intracerebral bloodvessels [10,11], reduced NO production [12][13][14][15] and an increase in vasoconstrictors EDN1 [16,19] and AngII, through upregulation of angiotensin-converting enzyme (ACE)-1 and downregulation of ACE-2 [17,18]) may all contribute to reduced cerebral blood flow (CBF). Reduced tissue oxygenation leads to increased VEGF [3,[29][30][31][32] that is not accompanied by an increase in endothelial von Willebrand factor (vWF) level and microvessel density [3].…”

“…Vessel wall abnormalities such as cerebral amyloid angiopathy (CAA) and arteriolosclerosis, may play a part in the hypoperfusion but its timing and distribution suggest that other factors are more important contributors. These include cholinergic denervation [10,11], reduced production of nitric oxide [12][13][14][15], and an increase in the intracerebral production of vasoconstrictors such as endothelin I and angiotensin II [16][17][18][19].…”

Cerebral Hypoperfusion and the Energy Deficit in Alzheimer's Disease

“…Stimulation of neurons in the nucleus basalis (see (26) (13,26). It should be noted that AD is also associated with alterations in a range of other neurotransmitters that have direct or indirect effects on vascular contractility, including glutamate, γ-aminobutyric acid, noradrenaline (norepinephrine), serotonin and dopamine (28,34,44,63,113).…”

“…The cholinergic system is, of course, already routinely targeted in AD patients through the administration of cholinesterase inhibitors. These drugs improve cerebral perfusion in mild to moderate disease (19), and several studies found evidence of an association between cognitive response and cerebral blood flow (13,26,124). The potential for intervention in the renin-angiotensin system has been extensively reviewed (56)(57)(58)(59) and the effects on cognition and cerebral blood flow of losartan, an angiotensin receptor antagonist, are currently being tested in a multicentre UK clinical trial (115).…”