Reduction of Regional Cerebral Blood Flow and Cognitive Impairment in Patients with Alzheimer's Disease: Evaluation of an Observer-Independent Analytic Approach

Abstract

The aim of the study was to evaluate an observer-independent semiquantitative analysis of brain imaging by single-photon emission computed tomography (SPECT) in patients with Alzheimer''s disease (AD). Patients (n = 45, mean age 70 ± 11 years) with a clinical diagnosis of AD according to NINCDS/ADRDA criteria were examined by ^99mTc-ethylcysteine dimer SPECT. Following anatomic normalization and data extraction using three-dimensional stereotactic surface projection, a pixelwise comparison of ECD uptake was performed with the reference values of 10 cognitive intact controls of comparable age. The global relative decrease of cerebral blood flow in cortical association areas showed a significant inverse association with the overall level of cognitive functioning as assessed with the Mini Mental State Examination and with the cognitive section (CAMCOG) of the Cambridge Mental Disorders of the Elderly Examination. There were significant region-specific associations between left temporoparietal perfusion deficit and language performance and between right temporoparietal regional cerebral blood flow reduction and praxis. The results suggest that this observer-independent analysis of SPECT data provides a valid assessment of the pattern and severity of cortical perfusion abnormalities in patients with AD.

Sympathetic α3β2-nAChRs mediate cerebral neurogenic nitrergic vasodilation in the swine

“…This is different from the reported findings that A␤ inhibits the ␣ 7 -nAChRs (13, 37) and ␣ 7 -nAChR-mediated cerebral vasodilation in LY pigs (40). This inhibition of ␣ 7 -nAChR-mediated vasodilation by A␤ (40) may provide a partial explanation for decreased cerebral blood flow in the early phase of AD (5,14,40), since A␤s play a key role in pathogenesis of AD. This inhibition by A␤ may also explain the upregulation of ␣ 7 -nAChR subunit protein in animal models of AD, as well as in human brain samples from AD patients (4,8,17).…”

“…The vasodilation is blocked by ␤-amyloid peptide (A␤) via inhibition of the ␣ 7 -nAChR (40). Because A␤ is a key causative factor in pathogenesis of Alzheimer's disease (AD), A␤-inhibition of cerebral nitrergic vasodilation is consistent with the reports that AD is closely associated with reduction in regional cerebral blood flow that may accelerate the pathological progress (5,14). Accordingly, inhibition by A␤ of ␣ 7 -nAChRs on the cerebral perivascular sympathetic nerves may play a role in diminished cerebral arterial function in pathogenesis of AD (39).…”

Regional Cerebral Blood Flow and Prognostic Evaluation in Alzheimer’s Disease

“…Recent data [39] comparing rates of glucose metabolism with that of [ 11 C]methionine accumulation, as measured by PET, support the view that tissue loss alone cannot explain the glucose hypometabolism of AD patients, which may actually reflect reduced synaptic activity at least in part. By reflecting tissue loss and probably synaptic dysfunction as well, metabolic and blood flow measurements are significantly related to the severity of the disease [21,40,41] and then may be expected to be linked with disease progression as well.…”

Effects of Long-Duration Administration of 1% Isoflurane on Resting Cerebral Blood Flow and Default Mode Network in Macaque Monkeys

“…CBF decrease has been seen in normal aging and is associated with cognitive decline (Birdsill et al, 2013;Hirsch et al, 1997;Jagust et al, 1992;Poels et al, 2008). CBF and cerebral metabolism can be altered by sedatives, analgesics, and anesthetics dramatically and the effects vary substantially from one drug to another (Van Aken and Van Hemelrijck, 1991;Werner, 1995).…”