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The strain this condition exerts on the healthcare system is increasing yearly. In spite of the large increase in the medication utilization over the previous years, the proportion of treated patients is still small, and further increase in their use is to be expected. It is necessary to monitor this in the years ahead.
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Lower pretreatment rCBF levels in the right orbitofrontal cortex (OFC) predicted a better improvement in the ADAS-cog score in response to donepezil therapy. The severity of SH did not appear to influence this correlation.
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Incidence of Alzheimer's disease is increasing globally and the current therapy is only symptomatic. Curative treatment is a major lacuna. NAR and RUT are natural flavonoids proven for their pleiotropic pharmacological effects with potential neuroprotective benefits. The study evaluated these flavonoids for their potential to improve the most common form of episodic memory (memory of autobiographical events in relation to time, places etc.) in two differential animal models assessing short-term and long-term memory, respectively. We also found that NAR and RUT were able to reverse both short-term and long-term memory deficits dose dependently in female Wistar rats. Abbreviations used: AD: Alzheimer's disease, AChE: Acetylcholinesterase, COX: Cyclooxygenase, DI: Discriminative index, ITI: Inter trial interval, NAR: Naringin, RUT: Rutin, NORT: Novel object recognition task, NOS: Nitric oxide synthase, QOL: Quality of life, RI: Recognition index, WFI: Water for injection.
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Prevention of neurocognitive decline in patients with brain metastases requires a multimodal approach tailored to each patient's need, avoiding WBRT in some, altering the WBRT plan in others, and/or using neuroprotective prophylaxis in those in whom avoidance cannot be utilized. Likewise treatment will require a personalized combination of strategies optimized to address the patient's symptoms.
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Ethanol extract of fresh LS leaves (LSEE), standardized on the basis of quercetin content, was successively partitioned using various solvents viz., hexane, ethyl acetate, and n-butanol in increasing order of polarity. LSEE (50, 100, and 200 mg/kg) and its various fractions (at a dose equivalent to dose of LSEE exhibiting maximum activity), administered orally for 14 days, were evaluated for their memory enhancing effect against scopolamine-induced (1 mg/kg, i.p.) amnesia in 3-4 months old male Laca mice (n = 6 in each group). The memory enhancing effect was evaluated using behavioural (elevated plus maze, novel object recognition and Morris water maze tests) and biochemical parameters (acetylcholinesterase activity, malonaldehyde, superoxide dismutase, nitrite, catalase, and reduced gultathione content). The results of the test substances were compared with both scopolamine and donepezil that was used as a standard memory enhancer and acetylcholinesterase inhibitor.
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We discuss a case of a 67-year-old male with dementia with Lewy bodies (DLB) that was initially suspected as Creutzfeldt-Jakob disease (CJD) or another type of encephalopathy, because he showed rapidly progressive deterioration, myoclonus, gait disturbance and a decline in activities of daily living. The present study describes a clinically atypical case with probable DLB and reviews similar cases in the literature, and we propose a rapidly progressive clinical subtype of DLB.
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Phencyclidine (PCP) induces a behavioral syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS) has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR) task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p.) or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP treatment. Acute treatment with modafinil (64 mg/kg, p.o.) ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c.), risperidone (0.2 mg/kg, i.p.), and donepezil (3 mg/kg, p.o.) were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP-NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS.
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The therapeutic approach is planned according to the different phases of the disease. In the preclinical phase, anti-inflammatory drugs and estrogens in post-menopausal women have been effective. In the initial phase current recognition therapy is directed basically towards correcting the break-down of acetylcholine (tacrine, donepezil, SB202026, SDZ ENA 713). For depressive symptoms serotonin levels are corrected using selective inhibitors of serotonin uptake.
Mice were given an intracerebroventricular (i.c.v.) injection of Abeta(25-35) peptide (9 nmol) 7-9 days before being tested for spontaneous alternation and passive avoidance. Hippocampal lipid peroxidation was measured 7 days after Abeta(25-35) injection to evaluate oxidative stress. Donepezil, the sigma(1) agonist PRE-084 or the cholinesterase (ChE) inhibitors tacrine, rivastigmine and galantamine were administered either 20 min before behavioural sessions to check their anti-amnesic effects, or 20 min before Abeta(25-35) injection, or 24 h after Abeta(25-35) injection and then once daily before behavioural sessions, to check their pre- and post-i.c.v. neuroprotective activity, respectively.
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One-year persistence rates were similar between different ChEIs. Among patients persisting with ChEI medication for at least 12 months, users of donepezil were slightly more likely to continue to persist at 24 months. Nearly half of patients failed to persist with ChEI therapy for at least 12 months. Our findings underscore the limitations of the ChEI medications and the urgent need for effective and tolerable therapeutic options for patients having dementia.