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The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a well-established instrument, designed to assess potentially remediable behavioral symptoms in Alzheimer's disease (AD) patients as well as to evaluate treatment outcome. It consists of 25 symptoms grouped into seven categories. Each symptom is scored on the basis of severity on a four-point scale. A knowledgeable caregiver is queried and items are scored on the basis of symptoms noted in the preceding two weeks. Reliability, construct validity and criterion validity data for the BEHAVE-AD have previously been published. Because of the significance of psychopathology in dementia, it is necessary to optimally describe and define the nature, magnitude and prevalence of behavioral symptomatology. Accordingly, a frequency component was added to each of the 25 items of the BEHAVE-AD scale. The objective of the present report is to describe this new Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) and to establish its inter-rater reliability. In this investigation the BEHAVE-AD-FW scale was administered to caregivers of 28 patients with either mildly impaired cognitive function or a dementia diagnosis. Two clinicians separately and independently rated the responses. Analyses determined that the intraclass correlation coefficients (ICCs) for the frequency component varied between 0.86 and 0.97 for each of the seven BEHAVE-AD categories (p(s) < 0.001). ICCs for the frequency-weighted scores (item severity score x item frequency score) ranged from 0.69 to 0.98 for the seven symptom categories (p(s) < 0.001). For the BEHAVE-AD-FW total scores, the ICC was 0.91 (P < 0.001). These results indicate that the frequency-weighted component is a reliable addition to the BEHAVE-AD scale.

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The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively impaired patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus (NPH). Cognition was measured by means of the global deterioration scale (GDS), the mini mental status examination (MMSE) and a battery of six psychometric tests. Gait was assessed using objective measurements of velocity and the ambulatory index (AI). The prevalence of cases exhibiting neuritic plaques (positive biopsies) increased in parallel with dementia severity from 18% for patients with GDS 3 to 75% for patients with GDS scores > or =6. Patients with positive biopsies were more cognitively impaired (higher GDS and lower MMSE scores) as well as more gait impaired (higher AI scores and slower velocities) than patients with negative biopsies. After surgery, gait velocity and AI scores improved significantly and to a comparable degree for patients with and without positive biopsies. Similar proportions of positive and negative biopsy patients also had improved gait as assessed by means of subjective video tape comparisons. There were no significant differences between the biopsy groups in the magnitude of postoperative psychometric change or in the proportion of cases exhibiting improved urinary control. Alzheimer's disease pathology is a common source of comorbidity in older patients with idiopathic NPH where it contributes to the clinical impairment associated with this disorder. For patients accurately diagnosed with NPH, concomitant Alzheimer's disease pathology does not strongly influence the clinical response to shunt surgery.

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Data from clinical, electrophysiologic, neurophysiologic, neuroimaging and neuropathologic sources indicates that the progression of brain aging and Alzheimer's disease (AD) deterioration proceeds inversely to human ontogenic acquisition patterns. A word for this process of degenerative developmental recapitulation, "retrogenesis", has been proposed. These retrogenic processes provide new insights into the pathologic mechanism of AD deterioration. An understanding of retrogenic phenonmena can also result in insights into the applicability of retrogenic pathologic mechanisms for non-AD dementing disorders. Management strategies based upon retrogenesis have recently been proposed. Retrogenic pathophysiology also points to previously unexplored pharmacologic approaches to dementia prevention and treatment.

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We investigated the reliability, using a telephone interview procedure, of cognitive, functional, and behavioral scales in an elderly population with normal aging and dementia. Two clinicians performed the assessments: one performed the assessments in a telephone interview format and the other conducted the assessments at the clinic. The telephone interview always preceded the clinic evaluation (2-30 days apart), and both clinicians were blind to any previous evaluations of the patient. The intraclass correlation coefficients between the telephone interview and the ratings obtained by a different clinician on the clinic evaluation varied between 0.92 and 0.98 (P's < or = .001) for comprehensive test scores. These results indicate that a telephone interview format, although not a substitute for a face-to-face diagnostic evaluation, is a reliable procedure for obtaining the assessment modalities studied. These findings are particularly important in aged and dementia research populations where personal contact may not always be feasible.

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Behavioral disturbances in dementia are some of the most burden-some features with which the caregivers must cope. These symptoms are particularly important because they are likely to be responsive to both pharmacological and nonpharmacological intervention strategies. Before the 1980s, rating scales for patients suffering from dementia did not separate cognitive features from noncognitive behavioral symptoms. This was a major problem because the evolution and course of behavioral symptoms in dementias, such as Alzheimer's disease, is different from the evolution and course of cognitive and cognition-related symptomatology. Before appropriate rating scales could be developed for the assessment of behavioral disturbances in dementia, the specific nature of these disturbances had to be described in the medical literature. Publications in the late 1980s described the specific behavioral disturbances occurring in dementia patients in detail for the first time. The rating scales that have been developed from these studies are as reliable as cognitive assessment measures. Instruments are now available that are based on information provided by the caregiver or that are based on observation of the patient made by the clinician. Construct validity, reliability, and the differences in methodology of these scales are compared in this overview. Using these scales will enable clinicians to assess pharmacological and nonpharmacological intervention strategies for behavioral symptoms in dementia with enhanced sensitivity.

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To address the issue of mild, moderate, and severe Alzheimer's disease (AD), it is necessary to initially establish some agreement on terminology. In recent decades, these terms have frequently been defined using screening instrument scores with measures such as the Mini-Mental State Examination (MMSE). There are many problems with this approach, perhaps the most salient of which is that it has contributed to the total and tragic neglect of patients with severe AD. An alternative approach to the classification of AD severity is staging. This approach has advanced to the point where moderately severe and severe AD can be described in detail. Procedures for describing this previously neglected latter portion of AD have recently been extensively validated. Staging is also uniquely useful at the other end of the severity spectrum, in differentiating early aging brain/behavior changes, incipient AD, and mild AD. Temporally, with staging procedures, it is possible to track the course of AD approximately three times more accurately than with the MMSE. The net result of the advances in AD delineation is that issues such as prophylaxis, modification of course, treatment of behavioral disturbances, loss of ambulation, progressive rigidity, and the development of contractures in AD patients can now be addressed in a scientifically meaningful way that will hopefully bestow much benefit in AD patients and those who care for them.

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The methods of synthesis and the pharmacological evaluation of a new non-tricyclic antidepressant drug, N-benzo[b]furan-2-ylcarbonyl-N'-benzylpiperazine (befuraline), are reported. The chemical structure of befuraline is clearly different from that of the tricyclic antidepressant drugs. While the gross behavior in animals remains unaffected, the central nervous system depressed by reserpine, tetrabenazine or perphenazine is activated by even small doses of this novel compound. Exploratory activity is prolonged, and performance in operant behavior tests and in the conditioned avoidance response is improved by befuraline, indicating increased alertness, attentiveness and the capacity to react to environmental stimuli. High doses stimulate the CNS, causing EEG desynchronization. Befuraline displays an aggression-inhibiting activity; without having a sedative effect on the animals' normal behavior, it inhibits fighting behavior. The central anticholinergic effect of befuraline is negligible. No apomorphine or tryptamine potentiation is observed and hexobarbital anesthesia is not influenced. The peripheral autonomic nervous system, with the exception of the nictitating membrane in cats, is not affected by befuraline. It has a biphasic effect on the norepinephrine induced contraction of isolated guinea pig seminal vesicle and of isolated cat spleen slices. Although the mechanism of action is as yet not clear, it is assumed that, in addition to a direct influence on the central adrenergic structures, the inhibition of norepinephrine and serotonin uptake and the inhibition of phosphodiesterase are responsible for the drug's effect. Befuraline has no undesirable effects on either the peripheral autonomic nervous system or the cardiovascular system, and it does not affect the normal gross behavior of animals. Because these favorable therapeutic aspects are coupled with low toxicity, befuraline may provide a new alternative in the treatment of depression.

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Pentoxifyline at 1 mM had no effect on [14C]isoleucine incorporation into mouse brain tissue suspension. At 5-20 mM, this compound inhibited incorporation. The inhibition was prompt, and it was reversible. Aminophyline at 3-12 mM produced inhibition, but theophyline at 2-16 mM had no effect. Pentoxifylline inhibited the incorporation of uridine into brain RNA to the same extent and with a similar time course as its effect on protein synthesis.

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