• Title: Faulty Regulation of Tau Phosphorylation by the Reelin Signal Transduction Pathway is a Potential Mechanism of Pathogenesis and Therapeutic Target in Alzheimer’s Disease.
    Date: February 2007
    Journal: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology
    Excerpt: Hyperphosphorylated tau protein is the basic structural component of the neurofibrillary tangle, a histopathological hallmark of Alzheimer’s disease. The formation of hyperphosphorylated tau protein may impair learning and the synaptic plasticity of neurons. Tau is a protein that is associated with and stabilizes microtubules; hyperphosphorylated tau protein is unable to perform this stabilization function. The transduction of reelin, a protein that is crucial to neuronal migration and the formation of synaptic connections in the fetal brain, may have an equally important role in regulating at least some forms of learning and synaptic plasticity in the fully developed mature brain. Reelin transduction is mediated by receptors in the brain that are members of the superfamily of low-density lipoprotein receptors. An important downstream target of reelin signal transduction appears to be inhibition of an enzyme involved in the regulation of tau phosphorylation. The faulty transduction of the reelin signal may be a pathological mechanism leading to hyperphosphorylation of tau protein. Ultimately, inhibition of tau phosphorylation may be an important therapeutic target in Alzheimer’s disease and other neuropsychiatric disorders.
  • Title: Psychosis and Physical Aggression in Probable Alzheimer’s Disease.
    Date: September 1991
    Journal The American Journal of Psychiatry
    Excerpt OBJECTIVE: The purpose of this study was to determine the frequency and type of psychotic symptoms in patients with probable Alzheimer’s disease and to test whether there is a relationship between specific psychotic symptoms and episodes of physical aggression. METHOD: From 209 patients with possible or probable Alzheimer’s disease who had been assessed in a research clinic every 6 months for up to 4.5 years, 181 subjects with probable Alzheimer’s disease were selected for study. On the basis of the summary note for each visit in the patients’ charts, the presence of delusions, hallucinations, misidentifications, and episodes of physical aggression was determined. Data regarding psychotic symptoms and aggression were available for 170 and 169 subjects, respectively. RESULTS: Delusions had been reported for 74 (43.5%) of the patients and were the most frequent psychotic symptom; persecutory delusions were the most common type. Physical aggression had been noted for 50 (29.6%) of the patients. Delusions and misidentifications frequently preceded and were significantly associated with episodes of physical aggression. The presence of delusions was a significant predictor of physical aggression but accounted for only 3.5% of the variance. CONCLUSIONS: This study suggests that delusions are a risk factor for physical aggression in patients with probable Alzheimer’s disease who have moderate to severe cognitive impairment. As delusions accounted for only a small percentage of the variance, further research is needed to identify other variables that may be significant predictors of physical aggression in this population.
  • Title: Agitation and Other Noncognitive Abnormalities in Alzheimer’s Disease.
    Date:August 1991
    Journal: The Psychiatric Clinics of North America
    Excerpt: Agitation and other noncognitive abnormalities in patients with Alzheimer’s disease are present in at least 50% of patients and are a serious problem for caregivers. Agitation can be divided into aggressive agitation, physically nonaggressive agitation, and verbal agitation. Persecutory delusions of suspiciousness and stealing are the most common psychotic symptoms. Auditory and visual hallucinations are also associated with delusions. Similar to delusions are misidentifications, which are false beliefs probably secondary to agnosia. They occur in one third of patients with dementia of the Alzheimer type in the form of the belief that strangers are living in the home and misidentification of the patient’s home and reflection in the mirror. Passive personality changes are present early in the disease, whereas agitation and psychotic symptoms occur with disease progression and predict a more rapid rate of cognitive decline. Agitation and wandering are related to more severe cognitive impairment and psychosocial variables, and neurochemical variables that may be related to behavior disturbance require further study. There are few systematic studies of behavioral or environmental interventions for behavioral symptoms in patients with Alzheimer’s disease. Current treatment emphasizes education of families, the formation of Alzheimer units in the nursing home, and adjunctive psychotropic agents to treat well-defined target symptoms.
  • Title: Memory for Temporal Order in Schizophrenia.
    Date: July 1991
    Journal: Biological Psychiatry
    Excerpt: Memory for temporal order information was examined in patients with chronic schizophrenia using the recency discrimination task. In this task, subjects were shown a pair of previously studied words and were asked to choose which one of the two words they had seen more recently. In addition, subjects performed the Wisconsin Card Sorting Test (WCST). The results showed that schizophrenic patients differed from normal control subjects in their performance on the recency discrimination task. In addition, for schizophrenic patients, performance on the recency discrimination task was inversely related to the number of perseverative errors on the WCST. These results provide further evidence of prefrontal-type cognitive deficits in schizophrenia.
  • Title: Agitation: Subtypes and Their Mechanisms.
    Journal: Seminars in Clinical Neuropsychiatry
    Excerpt: Agitation includes inappropriate verbal, vocal, or motor behaviors that, in the opinion of an observer, do not result directly from the needs or confusion of the agitated individual. Those behaviors affect the well-being of older persons and their caregivers, and therefore also the care rendered to the older person, including the likelihood of institutionalization. The inappropriate nature of agitated behavior is judged from the standpoint of an observer rather than that of the agitated person and may be subject to bias. Research to help clinicians disentangle the meaning of agitation and reduce the effects of observer bias has produced an approach to classification that is useful as a starting point. Agitated behaviors can be divided into physical and verbal, aggressive and non-aggressive. The available literature suggests that the different agitated behaviors have different meanings. Most seem to be associated with discomfort, which may include physical pain, external restraint, or feelings of depression or of loneliness. In contrast, some of the behaviors, especially in the physically nonaggressive category, may be adaptive and not an indication of discomfort. Other behaviors may result directly from neurological damage. On the basis of these interpretations of the reasons for disruptive behaviors, several approaches for treatment follow logically. Although there is much literature on behavioral, environmental, social, and pharmological approaches to treatment of agitation, large well-designed studies are conspicuously lacking. Both good intervention studies and improved methods for tailoring treatment to the specific needs and background of individual elderly persons are needed to better treat this complex phenomenon.