Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.
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PMID:Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease. 1160 28

The role of PET and SPECT brain imaging in the initial assessment and differential diagnosis of dementia is beginning to evolve rapidly. Numerous studies confirm the value of functional brain imaging, particularly with FDG-PET imaging, as a potentially cost-effective means of establishing an earlier diagnosis of Alzheimer's disease. Such an approach should allow for a more objective means of establishing which patients will benefit from treatment with cholinesterase inhibitors. In the future, neuroreceptor and plaque burden imaging studies should further enhance the sensitivity and specificity of dementia detection and patient management.
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PMID:Positron emission tomography and single-photon emission computed tomography brain imaging in the evaluation of dementia. 1260 58

Several guidelines for the evidence-based diagnosis and treatment of dementing disorders have been published in Germany and worldwide during the last years. This review analyses the content and methodological quality of 13 recently published dementia guidelines. There are some unequivocal recommendations for diagnostic procedures (e. g. clinical evaluation, neuropsychological screening, structural brain imaging) and treatment (e. g. cholinesterase inhibitors). There is a broad range of opinions on other procedures (e. g. routine EEG, FDG PET, cognitive training). A discussion of the prevalent guideline pluralism and a pleading for regionally adapted international guidelines conclude this article.
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PMID:[A systematic comparison of national and international dementia guidelines]. 1279 48

Dementia with Lewy bodies (DLB) is the second most common cause of dementia. The diagnosis of DLB is particularly important because these patients show good response to cholinesterase inhibitors. Clinical and neuroimaging criteria for DLB have not been acceptable for predictive accuracy. We report a case of progressive dementia in which the differentiation of DLB and Alzheimer disease (AD) on the basis of clinical criteria alone was not possible. The patient was admitted to the hospital because he became worse after he had started treatment for severe AD. Both MRI and brain magnetic resonance spectroscopy were normal. The patient underwent myocardial scintigraphy with I-123 MIBG showing marked reduction in cardiac MIBG accumulation. The heart to mediastinum ratio of MIBG uptake was impaired in both early and delayed images. FDG-PET scan before and after activation with a visual attention task showed occipital cortex hypometabolism as compared with AD and a normal control. This case illustrates the value of combining activated brain FDG PET and cardiac MIBG. The association of these 2 techniques could be used as a potential diagnostic tool in a patient with dementia misdiagnosed as AD.
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PMID:Value of combining activated brain FDG-PET and cardiac MIBG for the differential diagnosis of dementia: differentiation of dementia with Lewy bodies and Alzheimer disease when the diagnoses based on clinical and neuroimaging criteria are difficult. 1849 45

In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to be an important herb that exhibits sedative effects in insomnia, palpitation with anxiety, restlessness, and disorientation in humans. We previously reported that BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed that BT-11 could remedy stress-induced memory deficits in rats. In this study, the stress-induced memory impairments in rats were significantly reversed almost to the control level by BT-11 treatment. To seek an active component of BT-11 that plays an important role in antipsychotic effects, we compared BT-11 with 3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root extracts. However, the effects of TMCA were less or were not consistent with those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the levels of neural cell adhesion molecule (NCAM) in rat brains to the control levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory impairments through increment of glucose utilization and total NCAM levels in rat brains. In conclusion, BT-11 may be strongly effective against stress-induced amnesia in rats, through the combined effects of TMCA and other active components of BT-11.
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PMID:BT-11 improves stress-induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains. 1871 49

A subtle cognitive impairment can be detected early in the course of Parkinson's disease (PD). Executive, memory and visuospatial functions are specifically affected, but the underlying pathophysiological basis is not well elucidated yet and may be heterogeneous. The recent identification of a PD-related cognitive metabolic pattern (PDCP), including hypometabolism in associative frontal, parietal and posterior limbic structures, has integrated the classical notion of a striato-frontal syndrome at the basis of cognitive dys-function. Recent evidence suggests that whilst executive dys-function is seen in virtually all PD patients, visuospatial and memory impairment may share a higher risk for the subsequent development of dementia. By means of perfusion SPECT and [18F]FDG-PET, cortical dys-function may be highlighted since the early stages, it is more evident in PD patients with Mild Cognitive Impairment (MCI), and reaches the maximum in PD dementia (PDD). Posterior temporo-parieto-occipital dys-function in associative and limbic cortex, closely resembling that found in Alzheimer's disease patients, is found in PDD, with a more severe occipital hypometabolism and a relatively milder hypometabolism in medial temporal lobe structures. Furthermore, deficit of acetylcholinesterase (AchE) can be found by means of [11C]MP4A-PET already in early stage of PD, especially in posterior regions, then becoming more severe in PDD and in dementia with Lewy bodies (DLB). Administration of AchE inhibitors to PDD patients increased brain metabolism in bilateral frontal and left parietal regions, and left posterior cingulate. Finally, the recent availability of radiopharmaceuticals able to disclose amyloid brain deposition has allowed to demonstrate amyloid load in a part of patients with PDD, possibly due to diffuse rather than neuritic plaques. Brain PET and SPECT have strongly contributed to the understanding of the pathophysiology of cognitive impairment in PD and may serve as probes to monitor the effects of therapeutic interventions.
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PMID:Radionuclide brain imaging correlates of cognitive impairment in Parkinson's disease (PD). 2176 28

We conducted an open noncontrolled study of efficacy of repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) combined with acetylcholinesterase inhibitor (galantamine) therapy in 30 Parkinson's disease patients with cognitive impairment and higher level of gait disorders. Galantamine dose gradually increase to maximum of 16 mg/day (8 weeks) before rTMSand after that we start rTMS for 10 consecutive days. Cognitive, neuropsychiatric and motor symptoms were assessed clinically at baseline and at end of 10 weeks combined therapy using the Mini Mental State Examination (MMSE), Freezing Of Gait (FOG), Clinical Gait And Balance Scale (GABS), Tinetti scale, the clock drawing test, the Frontal Assessment Battery (FAB), PDQ-39 and Beck Depression Inventory (BDI). The metabolism in the frontal lobes, caudate nucleus, thalamus were assessed in 9 patients at baseline and end of rTMS by [18F]FDG-PET. Changes in total point scores on the scales at the ends of 10 weeks were compared with the baseline. Results were significant in the FOG (p = 0.00002), GABS (p = 0.000006), MMSE (p = 0.0001), FAB (0 = 0.003), PDQ-39 (p = 0.00009), BDI (p = 0.00004). Improvements in gait and decreases in freezing and falls were seen in the end of study period. Our study demonstrated the beneficial effect of rTMS of the DLPFC combined with acetylcholinesterase inhibitor treatment on metabolism in the frontal lobes, caudate nucleus, thalamus ([18F]FDG-PET), improving of gait and cognitive functions in PD patients.
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PMID:[New approach to gait disorders therapy in late stages of Parkinson's disease]. 2313 May 17

Clinical indications of amyloid imaging in atypical dementia remain unclear. We report a 68-year-old female without past psychiatric history who was hospitalized for auditory hallucinations and persecutory delusions associated with cognitive and motor deficits. Although psychotic symptoms resolved with antipsychotic treatment, cognitive and motor impairments remained. She further showed severe visuoconstructive and executive deficits, ideomotor apraxia, elements of Gerstmann's syndrome, bilateral agraphesthesia and discrete asymmetric motor deficits. Blood tests were unremarkable. Structural brain imaging revealed diffuse fronto-temporo-parietal atrophy, which was most severe in the parietal regions. Meanwhile, FDG-PET suggested asymmetrical fronto-temporo-parietal hypometabolism, with sparing of the posterior cingulate gyrus. A diagnosis of possible corticobasal syndrome (CBS) was made. Amyloid-PET using the novel tracer NAV4694 was ordered, and revealed significant deposition of fibrillar amyloid (SUVR 2.05). The primary diagnosis was CBS with underlying Alzheimer pathology and treatment with a cholinesterase inhibitor was initiated. Determination of underlying pathological CBS subtype is not simple even when based on extensive investigation including clinical presentation, atrophy patterns on MRI, and regional hypometabolism on FDG-PET. By contrast, amyloid imaging quickly confirmed Alzheimer pathology, and allowed rapid initiation of treatment in this complex case with early psychiatric symptoms. This case study illustrates the clinical utility of amyloid imaging in the setting of atypical cases seen in a tertiary memory clinic.
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PMID:Clinical Utility of Amyloid Imaging in a Complex Case of Corticobasal Syndrome Presenting with Psychiatric Symptoms. 2622 55