Drug Treatment Memory Dysfunction

Although the primary causes (or cause) of AD are not known, significant advances have furthered our understanding of the genetic and environmental factors, as well as the pathophysiological mechanisms, that can lead to AD. The latter has been a critical area of research, as it has given rise to therapies aimed at slowing the progression of AD. The neuropathological and biochemical changes in AD can be divided into two general areas: (1) structural changes and (2) alterations in neurotransmitter systems.

Structural changes. Structural changes in AD are concentrated in the cortical association regions and portions of the limbic system, and involve amyloid metabolism alterations, neurofibrillary tangles, neuritic plaques, synapse loss, and neuronal death. In the neocortex, large neurons are preferentially lost, relative to small neurons. Beta-amyloid proteins (they are major constituent neurotic plaques, which are the key lesion in Alzheimer's disease) accumulate in affected and unaffected regions of brain, but only in the association cortices and limbic regions does it evoke an inflammatory response that leads to tissue destruction and formation of neurofibrillary tangles.

Neurotransmitter systems. One of the most consistent findings in the brain of AD patients is the loss of cholinergic neurons (neurons that produce the neurotransmitter acetylcholine) in the nucleus basalis of Meynert (nbM). The nbM sends cholinergic projections to all areas of the neocortex, especially the temporal lobes and frontal and parietal association areas, and the indemnity of this system is essential for normal cognitive functioning. However, the major depletion of cholinergic neurons occurs in the temporal lobes. Other neurotransmitters are affected in AD, such as serotonin and norepinephrine, and they are though to be associated with the noncognitive behavioral symptoms of AD.