Efforts to improve our understanding of the pathophysiological mechanisms of Alzheimer’s disease and to test novel therapeutic approaches for the effective management of this condition started about four decades ago and yet about four decades of research and development (R&D) efforts have failed to yield any effective interventions for Alzheimer and other neurodegenerative diseases and this has even been considered as one of modern medicine’s greatest frustrations and challenge with a failure rate of nearly 99.6 % as compared with about (twenty percent) 20% success rate for cancer drugs. Currently, the cost of bringing an Alzheimer from the stage of discovery and development to the market is estimated at $5.6 billion, and the process takes 13 years from preclinical studies to approval by the FDA.
AD is a neurodegenerative brain disorder and is the leading cause of dementia that manifests clinically as progressive memory loss, speech and language disorders and other neuropsychiatric and neurobehavioral disturbances and impairments in the performance of activities of daily living (ADL). Although the etiology and pathophysiology of Alzheimer is not fully understood; however, from a neurological standpoint, the disorder is characterized by neurofibrillary tangles, neuritic plaques and progressive degeneration of cholinergic neurons in the nucleus basalis of Meynert.
Other predisposing factors may involve genetic influences including mutations in the amyloid precursor protein (APP) and the two presenilin genes, which are important in the development of early-onset familial AD. That is, it is possible for genetic factors to promote or accelerate deposition of beta-amyloid protein to form plaques, as well as abnormal phosphorylation of tau protein to form neurofibrillary tangles. Several biochemical factors have also been suggested in the development and progression of the disorder, such as oxidative stress, inflammation and hormonal deficiency (especially estrogen), and aging. It is also possible for aging to contribute to the pathologic development of Alzheimer’s disorder (Farlow, 1998).
Recently, it was discovered that adding the Alzheimer drug Memantine to treatment with a selective serotonin reuptake inhibitor may improve depressive symptoms, executive function, and other outcomes in older patients with both depression and cognitive impairments. The mechanism of action of Memantine is through the blockade of current flow through channels of N-methyl-d-aspartate (NMDA) receptors–a glutamate receptor subfamily that is involved brain function. This is also the first research on Alzheimer that will involve the use of Memantine to target the glutamate neuronal pathway for the treatment of Alzheimer. This is a significant breakthrough because other drugs that block NMDA receptor channels, such as ketamine, exhibit serious and often life-threatening deleterious effects.
The study was a twelve-month study that included ninety-five (95) patients within the mean age of seventy-two years (72) years with depression who was also managing the condition with Escitalopram in daily doses of between 5 and 20 mg (mean dose, about 11 mg). The participants were ranked using the Hamilton Depression Scale (HAM-D), and the mean score was calculated to be 17.8 showing that they did not have dementia but had subjective cognitive complaints, although some met criteria for mild cognitive impairment. After six months, the patients were found to have improved significantly in terms of improvement in depression and cognition.