Neuropathological factors Psychosis As discussed previously, AD and other dementias are brain disorders presenting with a broad range of neuropathological lesions. When evaluating the etiology of psychosis
in BPSD in AD, for example, researchers should not. only establish the presence of neuropathological findings that explain the symptoms, but should also evaluate whether these findings differ between AD patients with and without Inhibitors,research,lifescience,medical psychosis and nondemented psychotic patients. Fortunately, in recent years, a number of investigators have reported neuropathological findings that clearly differentiate the psychotic AD population from both schizophrenic and nonpsychotic AD patients. Specifically, AD patients with psychosis have increased Inhibitors,research,lifescience,medical neurodegenerative changes in the cerebral cortex, increased subcortical norepinephrine, reduced cortical and subcortical serotonin, and abnormal levels of paired helical filaments (PIIF)-tau protein in entorhinal and temporal cortices.15 Circadian
rhythm, (sleep-wake) disturbance It has been suggested that degeneration of the hypothalamic suprachiasmatic nucleus (SCN), the “biological clock” of the brain that imposes 24-hour rhythms Inhibitors,research,lifescience,medical in physiology and behavior, plays a key role in disturbed sleep-wake patterns.16 Degeneration of suprachiasmatic vasopressin cells has been demonstrated in postmortem studies on brain tissue of AD patients.17 Depression Inhibitors,research,lifescience,medical Major depression in dementia of the Alzheimer’s type (DAT) patients has been associated
with increased degeneration of brainstem aminergic nuclei, particularly the locus ceruleus, and relative preservation of the cholinergic nucleus basalis of Meynert. Associated increases in the number of senile plaques or neurofibrillary tangles in the neocortex or allocortex have not been found.18 In addition, modest, decreases in serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels have been found in AD patients. Anxiety, clinical trial agitation, and other BPSD syndromes To the best of our knowledge, no specific relationship has been established between anxiety, Inhibitors,research,lifescience,medical agitation, and other BPSD syndromes and specific neuropathological ANNUAL REVIEWS findings in AD or other dementias. AD and other dementias, however, affect large areas of brain tissue and cause deficits in a broad range of neurochemical systems including gamma ,-aminobutyric acid (GAB A), dopamine, substance P, and others.19 It. is possible that future research will reveal relationships between those deficits and specific BPSD syndromes. Psychological and environmental factors To date, no clear relationships between most BPSD syndromes and specific psychological and environmental factors have been established.20 However, Cohen-Mansfield et al8 have studied relationships between patient needs, the environment, and agitation. Although a complete review of the literature is beyond the scope of this article a number of issues clearly emerge.