Your doctor should have been familiar with galantamine for a decade already
galantamine (5 posts to August 2013)
And with these positive effects your doctor should immediately create a protocol on this!
Effect of high-frequency (5Hz) rTMS stimulating left DLPFC combined with galantamine on cognitive impairment after ischemic stroke and serum homocysteine and neuron-specific enolase
Guojin Hu
Xiuli Sun- Department of Geriatric Rehabilitation, Shanghai Second Rehabilitation Hospital, Shanghai, China
Objective: To investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with galantamine in patients with cognitive impairment after stroke and its effect on serum homocysteine (Hcy) and neuron-specific enolase (NSE) levels.
Methods: A total of 90 patients with cognitive impairment after the first ischemic stroke were enrolled. They were randomly divided into rTMS+ cognitive rehabilitation group, Galantamine + cognitive rehabilitation group, and rTMS+ Galantamine + cognitive rehabilitation group. All groups received routine medical treatment and limb rehabilitation treatment. The rTMS stimulation site was the left dorsolateral prefrontal cortex (left DLPFC), the magnetic stimulation frequency was 5 Hz, the magnetic stimulation intensity was 80% of the motor threshold level, and 3,000 pulses were given every day. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fugl-Meyer scale, and modified Barthel index, as well as rehabilitation scale and serum NSE and Hcy were evaluated before and after treatment (after 4 weeks).
Results: After 4 weeks of treatment, the scores of MMSE, MoCa scale, Fugl-Meyer scale, and modified Barthel index in the three groups were significantly higher than those before treatment (all p < 0.05), while the serum NSE and Hcy levels of the three groups were decreased. rTMS+ Galantamine + cognitive rehabilitation group had higher scale scores, and the difference between the three groups was statistically significant compared with the other two groups (all p < 0.05).
Conclusion: Cognitive rehabilitation combined with HF-rTMS and galantamine could improve the cognitive function of patients to the greatest extent, promote the recovery of physical activity, improve the self-care ability of daily life, and effectively reduce the serum HCY and NSE levels in patients with cognitive impairment after stroke. No randomized controlled trials of similar combination treatments have been reported. The better therapeutic effect may be related to the fact that galantamine combined with repetitive transcranial magnetism can activate the brain cholinergic system more extensively, promote brain neural remodeling through long-term potentiation and inhibit local neuroinflammatory responses in brain injury.
1 Introduction
Post-stroke cognitive impairment (PSCI), especially post-stroke dementia, seriously affects patients’ functional recovery, daily activities, and social functioning. PSCI is an independent risk factor affecting the prognosis of stroke. Professor Hachinski’s survey published in “Stroke” in 2006 showed that as many as 64% of stroke patients have varying degrees of cognitive impairment, and 1/3 will develop obvious dementia (1). A systematic review of epidemiological characteristics of post-stroke cognitive impairment in China in 2013 showed that the incidence rates of PSCI and post-stroke dementia (PSD) within 3 months after stroke were 56.6 and 23.2%, respectively (2). Compared with those without dementia, physical function of PSCI patients, their mental health status, and social functioning undergo more significant decline. Also, their functional independence is weakened, social participation ability is worsened, life satisfaction drastically decreases, and the 5-year survival rate is significantly lowered (3, 4). PSCI also seriously hinders the improvement of patients’ motor function, psychological state, self-care ability, and ability to participate in social activities and reduces life expectancy.
In recent years, non-invasive brain stimulation technology has developed rapidly, among which repetitive transcranial magnetic stimulation (rTMS) technology has received the greatest attention from researchers. rTMS acts on the central nervous system, mainly the brain, through a pulsed magnetic field, changing the membrane potential of neurons in the cerebral cortex, causing them to generate induced currents, affecting intramembrane metabolism and neural electrical activity, and inducing a series of physiological and biochemical changes. As a result, this technology has been widely investigated in recent years, producing positive effects on depression, cognitive impairment, post-stroke movement disorders, aphasia, etc. (5–7).
rTMS alters the excitability of cortical and subcortical neurons. Among them, high-frequency (>1 Hz) stimuli produce excitatory effects, and low-frequency (≤1 Hz) stimuli produce inhibitory effects. rTMS can act on synapses to produce long-term potentiation or long-term inhibitory effects and promote the excitation or inhibition of cortical neural circuits. Moreover, the physiological effects are persistent (8).
A large amount of available data indicates that TMS technology has a very unique role in the rehabilitation treatment of dementia, including degenerative dementias such as Alzheimer’s disease, as well as secondary dementias (mainly caused by vascular factors). Transcranial magnetic field can not only predict the risk of dementia in the brain, but also improve cognitive function by stimulating treatment to activate cholinergic neural pathways and promote brain injury remodeling. Existing transcranial magnetic studies have shown that patients with vascular dementia have increased motor cortex excitability (decreased resting motor threshold), which is consistent with patients with Alzheimer’s disease (9, 10). This may be part of a mechanism to compensate for plasticity after neuron loss and/or ischemic injury in the brain, with increased excitability helping to protect cognitive function. Abnormal resting motor threshold can be used as a “neurophysiological boundary point” to distinguish patients with normal cognition, non-demented vascular cognitive impairment, and vascular dementia (11). At the same time, the short-latency input inhibition measured by transcranial magnetic can reflect the function of cholinergic circuit in the central nervous system, which is closely related to cognitive function. Although there are some conflicting data in vascular dementia studies (12–14), this may be related to the variable location of subcortical infarctions in patients with vascular cognitive impairment and the significant differences in the distribution and extent of cholinergic denervation caused by them. Nevertheless, short latency inhibition holds great promise in the diagnosis and prognosis of different dementia processes and in the identification of acetylcholinesterase inhibitors for the treatment of sensitive individuals (15).
Transcranial magnetic therapy has a pleiotropic effect, although in a small number of experiments, the effects of high-frequency rTMS on mood, cognition, cortical microcircuits, neurotrophic/growth factors, and cerebral blood flow were not detected. This may be related to the selection of stimulus intensity, total pulse number, test sample size, sex selection, and the unclear mechanism of how ischemic brain injury affects plasticity induced by transcranial magnetic stimulation (16).
At present, there are many studies on the clinical application of rTMS in the treatment of post-stroke dementia, and gratifying results have been achieved (17, 18). Cha et al. (19) performed high-frequency transcranial magnetic therapy in patients with PSCI and assessed cognitive and emotional abilities at 2 and 14 weeks of treatment. The results showed that after rTMS treatment, the cognitive function of the patients was improved, and the proinflammatory cytokines in peripheral blood were decreased. These improvements lasted for three months. The meta-analysis by Li et al. (18) showed that the left dorsolateral prefrontal cortex of PSCI patients was stimulated by high-frequency rTMS, and the number symbol test, Rivermead behavioral memory test and the patients’ attention were significantly improved.
Galantamine hydrobromide is a second-generation cholinesterase inhibitor, initially used for the treatment of AD, which is highly selective for AChE in the central nervous system. It mainly inhibits cholinesterase at the synaptic cleft between the presynaptic membrane and the posterior membrane of brain cholinergic nerve cells, delays the degradation of acetylcholine, increases the content of available acetylcholine, stimulates and improves the function of the remaining acetylcholine receptors (20). The same time, after oral administration of Galantamine, the nicotinic cholinergic receptors in patients with vascular dementia can be regulated to a certain extent (allosteric regulation), and this change can promote a large amount of cholinergic nervous system in patients, releasing acetylcholine, promote its central nervous system into an excited state, and correct its memory and cognitive dysfunction. This unique dual action is beneficial for improving cognitive deficits in dementia patients.
Studies have shown that Galantamine has a good curative effect on patients with vascular dementia. In 2007, Auchus et al. (21) conducted a randomized, double-blind, and placebo-controlled clinical study involving multiple countries. Their results showed that the Galantamine group had significantly improved cognitive function and executive ability compared to the placebo group. In terms of improving activities of daily living, there was little difference between the two groups. The meta-analysis conducted by Yu-Dan et al. (22) showed that the treatment with donepezil and galantamine could significantly improve the Alzheimer’s disease cognitive scale (ADAS cog) score in patients with vascular dementia, with mild adverse reactions and high safety.
The treatment of PSCI requires early screening and detection and timely comprehensive intervention. Comprehensive intervention includes intervention and prevention of known risk factors, drug treatment, and rehabilitation. In addition, the recovery of cognitive function after stroke depends on repairing damaged nerve cells and cortical reconstruction, and intensive cognitive training can accelerate the process of cortical reconstruction. There is no ideal method for the treatment of PSCI, and the current treatment methods have poor efficacy. We attempted to combine high-frequency repetitive transcranial magnetic stimulation and galantamine oral therapy on the basis of cognitive rehabilitation therapy for PSCI patients, achieving better efficacy than the control group. The following report is presented.
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