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Biomedical subjects

D A Bennett

Publications and source records attributed to D A Bennett.

12 recordsLinked to original sources
PubMed1992

Clinical correlates of high signal lesions on magnetic resonance imaging in Alzheimer's disease.

The pathophysiology and clinical significance of high signal lesions, visualized on magnetic resonance imaging (MRI) in patients with Alzheimer's disease (AD), remain controversial. Since they are known to correlate with vascular disease and vascular risk factors, we reviewed the clinical correlates of periventricular high signal (PVH) and subcortical white matter lesions (WML) in a sample of 106 patients with probable AD, excluding persons with treated vascular risk factors or symptomatic cerebrovascular and cardiovascular disease. Grade 2 PVH were seen in 26 (25%) and scattered WML were identified in 29 (18%). PHV were associated with advancing age and gait disturbance. WML were associated with gait disturbance and incontinence. Neither radiologic finding was related to dementia severity. The findings suggest that these lesions are common in patients with AD even when those with evidence of cerebrovascular disease are excluded; their presence, therefore, should not preclude a diagnosis of AD. Additionally, the data suggest that HSL on MRI may be one of many risk factors associated with functional disability in persons with probable AD.

Aged↗
PubMed1992

Alzheimer's disease.

Alzheimer's disease is one of the most severe and most common chronic diseases of older persons. Because occurrence of the disease is strongly related to age, its public health impact is likely to continue to increase as the population ages. As with many other diseases, a diagnosis of Alzheimer's disease is made through a combination of clinical history, physical, and neurologic examination, and laboratory evaluation. Because the dominant feature of this disease is its effect on cognition, its diagnosis requires careful evaluation of cognitive function usually with formal neuropsychological performance testing. Clinical evaluation of persons for Alzheimer's disease has four objectives: (1) to determine as accurately as possible if the person has dementia; (2) if dementia is present, to determine whether its presentation and course are consistent with a diagnosis of Alzheimer's disease; (3) to assess evidence for any alternate diagnoses, especially if the presentation and course are atypical for Alzheimer's disease; and (4) to evaluate evidence of other, coexisting, diseases that may contribute to the dementia, with strong emphasis on conditions that might respond to treatment. There is no reliable antemortem diagnostic test for Alzheimer's disease; the main purpose of laboratory testing is to identify other conditions that might cause or exacerbate dementia. Pathologically, Alzheimer's disease is characterized by the presence of two lesions on microscopic examination of the brain: neuritic plaques and neurofibrillary tangles. Both lesions can be seen in the brains of older persons without dementia. However, they are found in greater numbers in the neocortex and hippocampus with Alzheimer's disease. Caring for patients with Alzheimer's disease is demanding and requires compassion and skills that go beyond the choices among sophisticated and effective therapies that characterize much of modern medical practice. The current lack of effective pharmacotherapy for cognitive dysfunction in Alzheimer's disease should not obscure that there are many areas in which intervention can improve quality of life for both the patient and the caregiver. Achieving success in these areas typically requires that the physician work effectively with providers of many other medical and nonmedical services. Community resources, advocacy, behavior management, and experimental therapies and procedures, should be discussed with the family of each patient. In addition, persons with mild disease should be promptly informed of their diagnosis in order to obtain their wishes regarding life prolonging measures and extended care options.

Aging↗
PubMed1991

Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones.

Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin- 5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e] [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.

Aggression↗
PubMed1991

Predictors of behavioral disturbance in Alzheimer's disease.

The relationship of behavioral disturbances in Alzheimer's disease to disease severity, age at onset, and the presence of extrapyramidal signs was investigated in three studies. Five categories of behavior disturbance were ascertained through structured interview with the patient's primary caregiver: apathy, agitation, psychotic symptoms, disinhibition, and irritability. In Study 1, measures of disease severity accounted for 42% of the variance in the Apathy scale but less than 20% of the variance in the remaining scales. In Study 2, the presence of extrapyramidal signs was associated with increased Apathy and moderated the association between disease severity and the Psychotic Symptoms and Irritability scales. In Study 3, age at onset was associated with the Agitation scale and moderated the association between disease severity and the Apathy, Psychotic Symptoms, and Irritability scales. The findings are discussed in terms of the clinical heterogeneity within Alzheimer's disease, the possible biological bases of these behavioral disturbances, and the psychometric issues pertinent to their measurement.

Age Factors↗
PubMed1991

Hallucinations and associated factors in Alzheimer's disease.

In a consecutive sample of 230 community-dwelling patients with probable Alzheimer's disease, a structured interview yielded evidence of current hallucinations in 29.1% and misperceptions in another 11.3%. Visual and auditory modalities were similarly represented in apparent hallucinations. Hallucinations prior to the current monitoring period were rare among patients with misperceptions or with no perceptual abnormality. The probability of hallucinations was associated with the severity of cognitive dysfunction, the degree of other behavioral disturbances, and the presence of extrapyramidal signs. A logistic regression model predicting hallucinations based on these diverse clinical features accurately classified 87.0% of the sample.

Activities of Daily Living↗
PubMed1991

Cessation of driving and unsafe motor vehicle operation by dementia patients.

We surveyed 522 consecutive patients from a dementia clinic to assess duration of driving after disease onset and instances of unsafe motor vehicle operation in the preceding 6 months. Among the 333 patients licensed to drive at the onset of dementia, the median duration of driving after onset was 28.6 months. Patients with a clinical diagnosis of Alzheimer's disease drove significantly longer than those with other dementia syndromes. Of the 93 patients still driving at the time of the survey, approximately one third were reported to have had at least one form of unsafe motor vehicle operation in the past 6 months, including 21 patients with motor vehicle accidents. Motor vehicle accidents were associated with use of prescription medications with sedative properties and with lower subjective ratings of the patient's driving ability by the informant.

Accidents, Traffic↗
PubMed1990

Diurnal blood pressure in patients with mild-to-moderate hypertension treated with once-daily benazepril hydrochloride.

This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride, a new angiotensin-converting enzyme (ACE) inhibitor, for mild-to-moderate hypertension. After a 2 to 4 week placebo baseline period, patients with diastolic blood pressure between 95 and 114 mm Hg, were randomized to receive either placebo or benazepril hydrochloride, 5, 10, 20, or 40 mg, once daily in double-blind fashion for 28 days. Blood pressure was measured predose and at 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period, and on the first and last day of the double-blind treatment period; and 24 hours after the dose at weekly outpatient visits. All doses of benazepril hydrochloride resulted in clinically important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose, and following the last dose after 4 weeks of treatment. The findings indicate that benazepril hydrochloride may be clinically useful as once-daily monotherapy in many patients with hypertension.

Administration, Oral↗
PubMed1990

CGS 19755: a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant, anxiolytic and anti-ischemic properties.

CGS 19755 is a potent and selective competitive antagonist at NMDA receptors in the brain. In preclinical animal tests, the compound produces anticonvulsant, anxiolytic and anti-ischemic effects. CGS 19755 is not very active when administered orally, and intravenous administration is the most practical for clinical application. The anti-ischemic potential of CGS 19755 provides the most attractive application for clinical investigation.

Animals↗