Psychiatry in old age
Ben Green in Problem-based Psychiatry, 2018
Dementias with treatable causes such as hypothyroidism and Wilson’s disease may wholly or partially remit with treatment. Other dementias such as Huntington’s are not yet treatable although research is ongoing. Alzheimer’s disease in recent years has been found to be slowed or inhibited in its course by agents such as the cholinesterase inhibitors. These include donepezil (Aricept), galantamine (Reminyl), and rivastigmine (Exelon). There are no major differences between these drugs and they all help to alleviate certain symptoms such as memory loss, apathy and anxiety. They may help patients remember new information and recall old information, improve alertness and motivation. Side-effects include nausea, loss of appetite, tiredness, diarrhoea, and sometimes sleep problems. They work by improving acetyl choline activity. Acetyl choline is used in the memory centres. Cholinesterase inhibitors reduce the destruction of acetyl choline and increase levels in the brain. Fifty to 60 per cent of people who take these drugs show a slight improvement or stabilisation of their condition. They are expensive drugs.
Dementia
Henry J. Woodford in Essential Geriatrics, 2022
Cholinesterase inhibitors may increase available acetylcholine within the brain of people with dementia and thus lessen the impact of neuronal loss. Donepezil, rivastigmine or galantamine are recommended for use in mild to moderate AD.115 Donepezil or rivastigmine are also recommended for DLB of any severity.28 Their use might be trialled in mixed dementia but not pure vascular dementia or FTD. They can provide a beneficial symptomatic, but not a disease-modifying, effect.89 In the UK, around 40% of people with AD are currently prescribed a cholinesterase inhibitor.116 Rivastigmine is also available in a transdermal patch formulation. This may reduce the incidence of gastrointestinal adverse effects. It may also be useful for those with an impaired swallow or reduced acceptance of tablets.
Neurotransmitters and pharmacology
Mark J. Ashley, David A. Hovda in Traumatic Brain Injury, 2017
Other than agonists, the only drugs used clinically to facilitate cholinergic neurotransmission are the inhibitors of acetylcholinesterase. These include the reversible cholinesterase inhibitors, such as physostigmine (Antilirium®), neostigmine (Prostigmin®), pyridostigmine (Mestinon®), and edrophonium (Tensilon®), that are used to treat or diagnose myasthenia gravis. Physostigmine crosses the blood–brain barrier, and others do not due to their highly charged molecular structure. Tacrine (Cognex®), donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Razadyne®) are also lipid-soluble reversible cholinesterase inhibitors that easily reach the brain. These drugs are approved for the treatment of memory and cognitive impairment associated with Alzheimer’s disease. Additionally, there are several irreversible inhibitors of cholinesterase, such as the organophosphates (e.g., diisopropylfluorophosphate or DFP), which irreversibly inhibit the enzyme and are used primarily as insecticides. However, some of these are present in eye drops for the treatment of glaucoma. Obviously, the irreversible cholinesterase inhibitors are extremely toxic and are of interest because of their toxicological effects. They are too dangerous for systemic use.
Can people with Alzheimer's disease improve their day-to-day functioning with a tablet computer?
Published in Neuropsychological Rehabilitation, 2018
Hélène Imbeault, Francis Langlois, Christian Bocti, Lise Gagnon, Nathalie Bier
BH, aged 65, has 16 years of education. She complains of cognitive problems that appeared gradually in 2010 and which have since intensified. Her memory problems interfere with her day-to-day functioning and her professional activities. In fact, she has stopped working because of her cognitive impairments. Following various clinical consultations (neurology, neuropsychology) and brain scans (CT-SCAN, PET SCAN), a diagnosis of probable Alzheimer's disease was made according to DSM-5 criteria (American Psychiatric Association, 2013). A cholinesterase inhibitor was administered and well tolerated. The medication was at a stable dose throughout the intervention. At the neuropsychological level, she underwent three assessments in which cognitive decline was confirmed (see Table 1 for a summary of the results of the third cognitive profile). The assessment was carried out two months before the beginning of the intervention.
Phytol loaded PLGA nanoparticles ameliorate scopolamine-induced cognitive dysfunction by attenuating cholinesterase activity, oxidative stress and apoptosis in Wistar rat
Published in Nutritional Neuroscience, 2022
Sethuraman Sathya, Boovaragamoorthy Gowri Manogari, Kaliannan Thamaraiselvi, Sethuraman Vaidevi, Kandasamy Ruckmani, Kasi Pandima Devi
Alzheimer’s disease is an age-related disastrous neurodegenerative disorder characterized by impaired memory function, disorientation, and behavioral changes. During the progression of the disease, AD patients gradually lose their ability to think, communicate, make judgments, and take care of themselves. Epidemiological studies show that about 26.6 million people worldwide are affected by AD, which will quadruple to 106.8 million by 2050 [1,2]. In spite of the great advancement in the clinical research field, AD treatment remains a formidable task because of the intricacy of the targets and cross signaling between several pathways involved. The major neuropathological hallmarks of are the accumulation of neuritic plaques, neurofibrillary tangles, oxidative stress, metabolic disturbances, neurotransmitter dependency, glutamatergic toxicity, neuroinflammation and disruption of calcium homeostasis, which leads to neuronal cell death[3]. Moreover, the correct pathomechanism of cognitive impairment and neuronal deterioration in AD is still ambiguous. Currently, the cholinesterase inhibitors are used for the symptomatic treatment of AD. The use of cholinesterase inhibitors overcomes the depletion of the neurotransmitter acetylcholine in the cerebral cortex and hippocampus region of the brain. However, these drugs have limitations in clinical use due to their short half-lives and severe side effects. Moreover, it is only effective against mild to moderate forms of AD[4].
Neuroprotective properties of solanum leaves in transgenic Drosophila melanogaster model of Alzheimer's disease
Published in Biomarkers, 2022
Opeyemi B. Ogunsuyi, Tosin A. Olasehinde, Ganiyu Oboh
Oxidative stress is considered a risk factor for the onset of AD (Cosín-Tomàs et al. 2019). Studies have shown that in AD patients, the brain is marked by oxidative stress associated with accumulation of Aβ and the deposition of neurofibrillary tangles (Christen 2000, Huang et al. 2016). Antioxidant therapy has also been globally accepted as therapeutic intervention for AD. Due to the established link between oxidative stress and pathogenesis and progression of AD, the use of antioxidants as preventive and management therapies have been well explored. Studies have shown that intake of antioxidants is linked with lower risk of dementia, AD and cognitive impairment in aged population (Grundman and Delaney 2002, Frank and Gupta 2005, Noguchi-Shinohara et al. 2018, Yeh et al. 2021). Therefore, several antioxidants and antioxidant-rich plant extracts have been reported promising for AD and cognitive impairments. Cholinergic system dysfunction is another important risk factor for AD. Cholinergic neurons utilise the neurotransmitter acetylcholine (ACh); these neurons have been shown to be involved in essential neurophysiological processes such attention, learning, memory, stress response, wakefulness and sleep, and sensory information (Picciotto et al. 2012 ). Damage to cholinergic neurons is believed to be involved in the etiology of AD and has been linked to cognitive impairment (Du et al. 2018). Hence, cholinesterase inhibitors were produced as a result, and they are still one of the most commonly used therapeutic medications to treat mild to moderate AD.
Related Knowledge Centers
- Cholinesterase
- Acetylcholine
- Butyrylcholine
- Chemical Synapse
- Muscarinic Acetylcholine Receptor
- Nicotinic Acetylcholine Receptor
- Acetylcholinesterase Inhibitor
- Butyrylcholinesterase
- Alzheimer's Disease
- Myasthenia Gravis