Dementia treatment

Psychiatric Mianserin has been investigated as a treatment for delirium [39 ]. However, in four elderly patients with dementia for 1.5-5 years, the addition of mianserin 30 mg/day to their existing dementia treatment resulted in acute delirium [40 ]. They recovered to their previous state when the mianserin was withdrawn. 

Other nootropic agents in some stage of clinical development include nebracetam (9), nefinacetam (10), and BMY 21502 (11). Nebracetam, an aminomethyl pyrrolidinone derivative, is expected to be approved in Japan in 1994 (73). In clinical studies involving patients having cerebrovascular or senile dementia of the Alzheimer s type, clinical symptoms such as spontaneous or emotional expression were enhanced in up to 71% of cases. Long-term treatment using nebracetam in patients with cerebral infarction also afforded marked improvement in most cases with few side effects (74). A review of this compound has beenpubUshed (75). 

The anainoacridines, tacrine (19) and its 1-hydroxy metaboUte, velnacrine (20), are reversible inhibitors of AChE. Tacrine was synthesi2ed in the 1940s and has been used clinically for the treatment of myasthenia gravis and tardive dyskinesia (115). Placebo-controUed studies have indicated modest efficacy of tacrine to treat AD dementia (122,123) and in 1993 the dmg was recommended for approval by the PDA under the trade name Cognex. Tacrine (19) has been shown to interact with sites other than AChE, such as potassium channels (124) and muscarinic receptors. However, these interactions are comparatively weak and are not thought to contribute to the biological activity of the dmg at therapeutic levels (115). 

Antipsychotic medications are indicated in the treatment of acute and chronic psychotic disorders. These include schizophrenia, schizoaffective disorder, and manic states occurring as part of a bipolar disorder or schizoaffective disorder. The co-adminstration of antipsychotic medication with antidepressants has also been shown to increase the remission rate of severe depressive episodes that are accompanied by psychotic symptoms. Antipsychotic medications are frequently used in the management of agitation associated with delirium, dementia, and toxic effects of both prescribed medications (e.g. L-dopa used in Parkinson s disease) and illicit dtugs (e.g. cocaine, amphetamines, andPCP). They are also indicated in the management of tics that result from Gilles de la Tourette s syndrome, and widely used to control the motor and behavioural manifestations of Huntington s disease. 

ChEI treatments have been expanded also to include other dementias and CNS disorders, e.g. delirium, traumatic brain injuries and memory impairments, as well as myasthenia gravis, glaucoma and parasite infections. 

Delirium, e.g. post-narcotic delirium, somnolence or coma, is a common complication involving dementia, with fluctuating attention and consciousness and considerable morbidity. It is not always reversible and there is no specific treatment. Some of the accompanying central cholinergic syndromes can be reversed by ChEIs. 

In addition to such direct advantages, pervasive computing has a big social contribution to make. It can be used, for example, to enable patients and their relatives to keep in touch, and to help people with cognitive disabilities function on a daily basis. One illness that lends itself to such treatment is senile dementia, which is likely to be a growing trend in the graying populations of the Western World. 

People with dementia and their carers require access to a variety of health and social care services for treatment, information and counselling, community-based support, respite care and long-term residential care. Treatment may include behavioural therapies (e.g. reality orientation, cognitive stimulation and validation therapy) or pharmacological treatment with acetylcholinesterase inhibitors. 

Treatment of neurons with dualtropic X4R5 gpl20 has been shown to induce cytochrome c accumulation and caspase 9, 8, and 3 activation (Garden et al. 2002). Incidentally in the same studies, activated caspase 3 immunoreactivity was found in the brains of neuroAIDS patients. Furthermore, caspase 3 activation was found to be involved in the synaptic and dendritic injury (Garden et al. 2002). Chronic dendritic disrnption has been correlated with the severity of HIV-related dementia (as reviewed in Ellis et al. 2007). 

Supplementation with antioxidant micronutrients, for example, vitamin E and selenium, in the elderly and in dementia subjects (Tolonen et al., 1985) has indicated that such treatments may be of some limited benefit. The value of ascorbate as a cerebroprotective antioxidant against excitotoxic neuronal injury has been proposed (Griinewald, 1993). 

The ChE inhibitors all have the indication for the treatment of mild to moderate dementia of the Alzheimer s type. Guidelines for the treatment of AD were written before the approval of memantine and recommend the use of ChE inhibitors as a valuable treatment for AD.27-29 None of the ChE inhibitors have been compared in head-to-head studies, so the decision to use one over another is based on differences in mechanisms of action, adverse reactions, and titration schedules. 

Donepezil is approved for the treatment of mild to moderate dementia of the Alzheimer s type at a dose of 5 mg/day. This dose should be increased to 10 mg/day if needed after 4 to 6 weeks. Table 32-5 describes the dosing strategies for all of the approved agents for Alzheimer s disease.34-38... 

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