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Biomedical subjects

S Salloway

Publications and source records attributed to S Salloway.

At least 19 recordsLinked to original sources
PubMed2004

Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI). METHODS: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations. RESULTS: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient. CONCLUSION: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.

Aged↗
PubMed2002

Effect of APOE genotype on microvascular basement membrane in Alzheimer's disease.

APOE4 homozygosity has been associated with an increased risk of sporadic Alzheimer's disease through a mechanism, which has yet to be defined. Recent evidence has suggested that microvascular basement membrane injury may be a critical factor in the pathogenesis of AD-related dementia. In previous studies, we have shown that the synaptic organizing protein agrin can be found in neurons, and is a major component of the brain microvascular basement membrane. Here, we compare the basement membrane surface area of cortical microvasculature in AD brains by staining with an anti-agrin antibody. Quantitative morphometric analysis was used to determine the mean basement area (micro(2)) of prefrontal cortical microvessels. An average of 10 capillaries was measured in each of 35 cases of AD genotyped for APOE status. APOE4,4 homozygotes had smaller capillary basement membrane areas (17.4 micro(2))+/-6.2) than APOE3,3 homozygotes (26.9 micro(2)+/-6.5), p<0.001. The capillary basement membrane areas (CBMA) of heterozygotes APOE3,4 did not differ significantly from APOE3,3 or APOE4,4. Braak stage did not contribute significantly to CBMA. However, a preliminary analysis suggests an interaction between APOE4,4 and Braak V-VI producing smaller CBMA, a finding which needs to be confirmed with a larger sample. These data support the hypothesis that APOE4,4 is associated with thinning of the microvascular basement membrane in Alzheimer's disease.

Aged↗
PubMed2001

The impact of behavioral symptoms on activities of daily living in patients with dementia.

The authors examined whether scores on two recently developed measures of behavioral disturbance, the Frontal Lobe Personality Scale (FLOPS) and the Neuropsychiatric Inventory (NPI), are associated with functional impairments in patients with dementia. Caregivers of 30 dementia patients were administered the FLOPS Family Form, the NPI, and an Activities of Daily Living (ADL) scale. Findings indicated a relationship between behavioral changes and functional limitations in patients with dementia. Moreover, the FLOPS, an instrument designed to specifically measure behaviors subserved by frontal lobe systems, was more strongly related to failures in instrumental ADLs than was the NPI. The authors conclude that behavioral measures add information over and above that available from cognitive tests in determining ADL functioning.

Activities of Daily Living↗
PubMed2000

Prediction of functional status from neuropsychological tests in community-dwelling elderly individuals.

Age-related dysfunction of frontal systems can result in deficits in planning, organization, self-control, and awareness of problems, which are likely to affect the ability to care for one's self. The purpose of this study was to determine the relationship between age-related frontal/executive deficits and impairment in instrumental activities of daily living (IADLs) in elderly individuals. Twenty-seven community-dwelling individuals were administered a comprehensive battery of neuropsychological tests and a performance-based evaluation of IADLs. Multiple regression analyses indicated that executive function and depression severity accounted for a significant proportion of variance in IADLs, with executive function making the greatest contribution. Tests measuring other cognitive functions, such as memory, language, and spatial skills, did not contribute significantly to the prediction of functional status. Furthermore, executive measures accounted for more variance than other demographic characteristics such as general health status, age, and educational level. The results of this study indicate that executive dysfunction in normal aging may be the best predictor of functional decline. A better understanding of the mechanisms that underlie IADL skills will ultimately aid in the development of compensatory and intervention strategies designed to delay the onset of assisted living and nursing home placement.

Activities of Daily Living↗
PubMed1999

Pharmacologic efficacy in neuropsychiatry: a review of placebo-controlled treatment trials. A report of the ANPA Committee on Research.

Psychiatric disorders frequently compound the disability and complicate the management of neurologic conditions. These disorders result in increased morbidity for the person afflicted, stress for the caregiver, and financial burden. This study reviews the randomized double-blind placebo-controlled pharmacologic treatment trials of psychosis, depression, anxiety, and agitation in neurologic conditions from 1966 to 1998. Ten studies involving psychosis, 13 involving depression, and 20 involving anxiety-agitation meeting the committee's criteria were identified. Relatively few randomized double-blind placebo-controlled pharmacologic treatment trials of psychiatric disorders complicating neurologic disease have been conducted. These trials do not strongly support one specific pharmacologic approach to treatment. Further study of newer psychotropic agents, augmentation strategies, and novel use of other agents may help improve the treatment of psychiatric disorders observed in patients with neurologic disease.

Humans↗
PubMed1999

Alteration of intention and self-initiated action associated with bilateral anterior cingulotomy.

Neuropsychological manifestations of bilateral anterior cingulate cortex lesions were studied in patients treated with cingulotomy for chronic intractable pain. Cingulotomy patients more than 1 year postsurgery were contrasted with nonsurgical chronic pain patients. Patients were assessed on a neuropsychological battery, including measures of response intention, initiation, generation, and persistence. Cingulotomy patients were intact across most cognitive domains, but they showed deficits of focused and sustained attention as well as mild executive dysfunction. Self-initiated responding--including spontaneous verbal utterances and unstructured design fluency--was most impaired. Results indicate that the greatest impact of cingulotomy lesions is on response intention and self-initiated behavior, with reduced behavioral spontaneity.

Adult↗
PubMed1998

Memory processes in depressed geriatric patients with and without subcortical hyperintensities on MRI.

In this study, 12 patients over age 60 with depression with moderate to severe subcortical hyperintensities (SH) localized to the periventricular white matter were identified by quantitative MRI. Using the California Verbal Learning Test, they were compared with 12 age-, education-, and severity-matched patients with depression with minimal white matter changes on specific aspects of memory performance. Patients with cortical lesions, neurologic or systemic illness affecting cognition, and history of substance abuse were excluded. Patients in the group with high SH showed reduced use of semantic encoding strategies (p < 0.05), reduced learning efficiency (p < 0.05), and a greater discrepancy between free recall and recognition discriminability (p < 0.05) than their low SH counterparts. This pattern of performance on memory tasks is similar to that found in previous studies to be associated with subcortical degenerative disorders such as Huntington's and Parkinson's diseases. Geriatric patients with depression with SH may represent a subgroup with greater subcortical involvement, with associated cognitive and functional decline.

Aged↗
PubMed1998

The clinician-scientist in neuropsychiatry: a position statement from the Committee on Research of the American Neuropsychiatric Association.

Neuropsychiatric research seeks to improve the lives of patients with brain-based behavioral disturbances. There has been dramatic progress in diagnosis and treatment of neuropsychiatric disorders, and progress in neuroscience and biotechnology promises further success. Paradoxically, recent trends threaten to erode this progress. In this environment, neuropsychiatric clinician-scientists must advocate for the importance of research. This position statement defines neuropsychiatric research, describes current challenges to the neuropsychiatric clinician-scientist, summarizes research opportunities, describes how future neuropsychiatric clinician-investigators should be trained, and makes recommendations for promoting neuropsychiatric research.

Career Choice↗
PubMed1998

CADASIL syndrome: a genetic form of vascular dementia.

Mental disorders due to cerebral microvascular disease have been known for over 100 years. Recently, an autosomal dominant form of cerebral arteriopathy (CADASIL) has been described in association with a Notch3 family gene on the short arm of chromosome 19. CADASIL causes subcortical lacunar infarction and dementia in over 80% of cases and depression in a large proportion of patients. Clinically, CADASIL may appear to be very similar to hypertensive microvascular disease (Binswanger's disease), a condition that is seen in the elderly. This article reviews the clinical, pathologic, and genetic features of CADASIL. CADASIL is of interest to neurologists and psychiatrists because it is the first syndrome of vascular dementia and depression with an identified gene. How the gene causes the widespread arteriopathy is not yet known. Insights gained from the study of CADASIL should help us better understand its etiology, as well as the options for treatment of the more common forms of microvascular disease seen in the elderly.

Aged↗
PubMed1997

Cognitive screening instruments in neuropsychiatry: a report of the Committee on Research of the American Neuropsychiatric Association.

A 1994 survey by the Research Committee of the American Neuropsychiatric Association revealed that 58% of respondents employed formal assessment of cognitive status; the Mini-Mental State Examination (MMSE) and neuropsychological testing were the commonest techniques. Literature review on common cognitive screening instruments found that the MMSE has widespread popularity, ease of use, and a large body of research demonstrating its sensitivity to common neuropsychiatric disorders. The Committee recommends that clinicians who employ the MMSE 1) use it as a minimum screening for cognitive dysfunction; 2) employ age- and education-normative corrections; and 3) supplement it with specific measures of spatial functions, delayed memory, and executive abilities. The Modified MMSE and the Neurobehavioral Cognitive Status Examination also show promise as screening tools.

Adolescent↗
PubMed1997

The limbic system: an anatomic, phylogenetic, and clinical perspective.

The limbic system is the border zone where psychiatry meets neurology. The authors provide a model of limbic function that combines phylogenetic, anatomic, functional, and clinical data to interpret diseases relevant to neuropsychiatry. They provide evidence supporting two major divisions in the limbic system: a paleocortical division with the amygdala and orbitofrontal cortex at its center, and an archicortical division with the hippocampus and cingulate cortex at its center. The implicit integration of affect, drives, and object associations is the function of the paleocortical limbic division; explicit sensory processing, encoding, and attentional control is the function of the archicortical limbic division. The two work in concert to integrate thought, feeling, and action. Understanding their development and organization informs us about how best to care for our patients.

Animals↗
PubMed1997

Paroxysmal limbic disorders in neuropsychiatry.

Patients who experience episodes with a transient disturbance in perception, memory, mood, and level of anxiety are frequently encountered by neurologists, psychiatrists, and psychologists. The possibilities for differential diagnosis of these episodes include partial complex epilepsy, psychogenic seizures, panic disorder, dissociative states, migraine, and transient global amnesia, among others. The clinical history may be vague and confusing, making it difficult to determine definitively the etiology of the events. This article describes a spectrum of paroxysmal disorders involving limbic structures, highlighting the clinical features and assessment techniques that aid in diagnosis and treatment. Clinical-anatomic correlations are provided whenever possible.

Adult↗
PubMed1997

Neuropsychiatric factors in the illusion of visitors among geriatric patients: a case series.

The 'illusion of visitors' is a common phenomenon among geriatric patients presenting for psychiatric or neurologic evaluation and treatment. Although these illusory beliefs are etiologically diverse, patients may commonly have visual impairment and functional and/or structural disruption of frontal and right-hemisphere-mediated cognitive functioning. This article outlines eight cases of illusory beliefs among elderly patients, presenting psychiatric, neurologic, neuroimaging, and neuropsychological findings among these patients. Commonalities and differences among these cases are discussed, and a framework is provided for multidisciplinary assessment and treatment of patients presenting with illusory beliefs.

Aged↗
PubMed1997

The diagnosis and treatment of post-stroke depression.

Depression is common after stroke but the diagnosis may be difficult. Anterior and subcortical brain lesions increase the risk of depression. It is important to make an accurate diagnosis of PSD as treatment may reduce morbidity. Treatment should consist of family support, education and anti-depressant medication.

Aged↗
PubMed1996

Miller-Fisher syndrome associated with Campylobacter jejuni bearing lipopolysaccharide molecules that mimic human ganglioside GD3.

A Campylobacter jejuni strain of serotype O:10 was isolated from a patient who had Miller-Fisher syndrome. In its biochemical reactions and cellular morphology, the isolate was characteristic of typical C. jejuni. Antibodies against extracted lipopolysaccharide (LPS) were detected by passive hemagglutination in the acute- and convalescent-phase patient sera. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with the O:10 antiserum, it was demonstrated that the strain possessed both low- and high-molecular-weight molecules. Chemical analysis of the LPS revealed that the core oligosaccharide has a terminal trisaccharide epitope consisting of two molecules of sialic acid linked to galactose, a structure reflecting the terminal region of human ganglioside GD3. As this trisaccharide is also present in LPS cores of serotype O:19 strains from patients with Guillain-Barré syndrome but not in cores of nonneuropathic C. jejuni, a possible role for the trisaccharide in the etiology of neuropathies is indicated, and a difference for distinguishing neuropathic strains from nonneuropathic strains may be the presence of a sialyltransferase required for the synthesis of this trisaccharide.

Acute Disease↗